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金沢貴憲

徳島大学

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2024年5月17日更新

職名: 教授
電話: 研究者総覧に該当データはありませんでした。
電子メール: kanazawa@tokushima-u.ac.jp
学歴: 2006/3: 東京薬科大学大学院薬学研究科博士前期課程修了
学位: 博士(薬学) (東京藥科大學) (2010年7月)
職歴・経歴: 2006/4: 東京薬科大学薬学部助手
2011/1: 東京薬科大学薬学部助教
2016/4: 東京薬科大学薬学部講師
2017/4: 日本大学薬学部専任講師
2020/4: 静岡県立大学薬学部准教授
2023/7: 徳島大学医歯薬学研究部(薬学域) 教授

専門分野・研究分野: ナノテク・材料 (Nanotechnology/Materials) [ナノ材料科学 (Nanomaterials)]
ライフサイエンス (Life sciences) [医療薬学 (Clinical pharmacy)]
ライフサイエンス (Life sciences) [生体材料学 (Biomaterials)]
ライフサイエンス (Life sciences) [薬系分析、物理化学 (Pharmaceuticals - analytical and physicochemistry)]

研究者総覧で最新データを確認する

2024年5月17日更新

専門分野・研究分野: ナノテク・材料 (Nanotechnology/Materials) [ナノ材料科学 (Nanomaterials)]
ライフサイエンス (Life sciences) [医療薬学 (Clinical pharmacy)]
ライフサイエンス (Life sciences) [生体材料学 (Biomaterials)]
ライフサイエンス (Life sciences) [薬系分析、物理化学 (Pharmaceuticals - analytical and physicochemistry)]
担当経験のある授業科目: コアDDS講義 (学部)
医療における人間学 (学部)
医薬品安全性学特論 (大学院)
医薬品開発特論 (大学院)
専攻公開ゼミナール (大学院)
演習3 (学部)
物理化学1 (学部)
生物化学実習 (学部)
育薬共通演習 (大学院)
臨床薬物動態学特論 (大学院)
薬学演習 (大学院)
薬学課題研究 (大学院)
薬物治療学1(循環器) (学部)
薬理学 (学部)
薬科学演習1 (大学院)
薬科学特別研究 (大学院)
製剤学 (学部)
指導経験: 研究者総覧に該当データはありませんでした。

研究者総覧で最新データを確認する

2024年5月17日更新

専門分野・研究分野: ナノテク・材料 (Nanotechnology/Materials) [ナノ材料科学 (Nanomaterials)]
ライフサイエンス (Life sciences) [医療薬学 (Clinical pharmacy)]
ライフサイエンス (Life sciences) [生体材料学 (Biomaterials)]
ライフサイエンス (Life sciences) [薬系分析、物理化学 (Pharmaceuticals - analytical and physicochemistry)]

研究テーマ: 研究者総覧に該当データはありませんでした。

著書

金沢貴憲 :
製剤の達人による製剤技術の伝承製剤設計・製造技術 BASIC & FRONTIER 岡田弘晃，川上亘作監修, --- (トピックス)Nose-to-Brain研究 ---,
株式会社じほう, 東京, 2023年5月. Takanori KANAZAWA :
Polymer micelles for drug delivery (Kesharwani P & Greish K, ed.), --- Chapter 18: Nose-to-brain delivery ---,
Elsevier, Aug. 2022. 金沢貴憲 :
中分子創薬に向けたDDS開発の新展開, 杉林堅次監修, --- 第2章鼻-脳輸送機構を基盤とする中枢標的DDSナノキャリアの開発 ---,
株式会社シーエムシー出版, 東京, 2022年3月. 茨木ひさ子, 金沢貴憲 :
中分子創薬に向けたDDS開発の新展開, 杉林堅次監修, --- 第9章細胞間隙を標的としたsiRNA組織内浸透型DDSの設計 ---,
株式会社シーエムシー出版, 東京, 2022年3月. Takanori KANAZAWA :
Design, Development and Applications (Oba M & Demizu Y, ed. ), --- Chapter 16: Polymer micelle, Cell-penetrating peptides ---,
Wiley-VCH Verlag GmbH & Co., 2022. 金沢貴憲 :
医薬品開発における中分子領域(核酸医薬・ペプチド医薬)の開発戦略, --- 第2章第2節核酸医薬におけるDDS技術の概要 ---,
情報機構, 東京, 2019年10月. Takanori KANAZAWA and Hiroaki Okada :
Mucosal delivery of biopharmaceuticals: Biology, challenges and strategies (Neves J and Sarmento B ed.), --- Delivery strategies for developing vaginal DNA vaccine combinating cell-penetrating peptide and jet injection ---,
Springer Science+Business Media New York, Feb. 2014. 岡田弘晃, 小河崇也, 田中晃, 金沢貴憲 :
ドラッグデリバリーシステムの新展開II ―核酸医薬・抗体医薬・ワクチン医療を支えるDDS技術―, 永井恒司, 岡田弘晃監修, --- 細胞質感受性核酸 DDS ---,
株式会社シーエムシー出版, 東京, 2012年3月. 岡田弘晃, 小河崇也, 田中晃, 金沢貴憲 :
先端バイオマテリアルハンドブック, --- 機能性ペプチドを用いた細胞質応答性siRNAキャリア ---,
株式会社シーエムシー出版, 東京, 2012年. 岡田弘晃, 金沢貴憲 :
次世代バイオ医薬品の製剤設計と開発戦略, 森下真莉子監修, --- 膣粘膜 DNA ワクチン ---,
株式会社シーエムシー出版, 東京, 2011年.

論文

Naoto Suzuki, Hiroaki Tanigawa, Taiki Nagatomo, Hiroko Miyagishi, Takanori KANAZAWA, Toyofumi Suzuki and Yasuhiro Kosuge :
Utility of a Novel Micro-Spraying Device for Intranasal Administration of Drug Solutions to Mice,
Pharmaceutics, Vol.15, No.11, 2553, 2023.

(要約): Intranasal administration has attracted attention as a means of delivering drugs because it bypasses the blood-brain barrier. However, conventional intranasal administration of drug solutions to mice using the micropipette method (MP method) is complicated and time-consuming because it requires small doses to be administered under inhalation anesthesia. This study evaluated the effectiveness of a novel intranasal administration method using Micro FPS™, a novel micro-spraying device (the MSD method). The MSD method allowed more reliable administration of the solution to the nasal mucosa than the MP method did. The transfer of inulin, a model water-soluble macromolecule compound, to the olfactory bulb and brain (cerebrum, cerebellum, brainstem, and striatum) was similar with the two methods. It also allowed the drug to be administered in a shorter time. These results suggest that the MSD method is simpler and more rapid than the MP method for intranasal administration of drugs to mice and achieves comparable delivery of inulin to the olfactory bulb and brain. Therefore, the Micro FPS™ device is a potentially useful tool for intranasal drug administration to rodents and could facilitate the development of intranasal formulations, contributing to drug development for central nervous system diseases.
(出版サイトへのリンク): ● Publication site (DOI): 10.3390/pharmaceutics15112553
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 38004533; ● Search Scopus @ Elsevier (PMID): 38004533; ● Search Scopus @ Elsevier (DOI): 10.3390/pharmaceutics15112553

(DOI: 10.3390/pharmaceutics15112553, PubMed: 38004533) Takayuki Terukina, Jun Tanaka, Yumi Takayama, Kaede Osanai, Shusuke Kino, Takanori KANAZAWA and Hiromu Kondo :
Sangelose-based gels and films: effects of glycerol and α-cyclodextrin and their pharmaceutical application.,
Drug Development and Industrial Pharmacy, Vol.49, No.1, 75-83, 2023.

(要約): To evaluate the possible application of Sangelose as an alternative to gelatin and carrageenan for the development of film substrates, and to examine the effect of glycerol and α-cyclodextrin (α-CyD) on the viscoelastic properties of Sangelose-based gels and the physical properties of the films. Sangelose-based gels/films can serve as a potential viable alternative to gelatin and carrageenan in pharmaceutical applications. Glycerol (a plasticizer) and α-CyD (a functional additive) were added to Sangelose, and gels and films were prepared. The gels were evaluated by dynamic viscoelasticity measurements, and the films were evaluated by scanning electron microscopy, Fourier-transform infrared spectroscopy, tensile tests, and contact angle measurements. Soft capsules were prepared using the formulated gels. The strength of the gels was affected when only glycerol was added to Sangelose and α-CyD addition resulted in rigid gels. However, the addition of α-CyD with 10% glycerol weakened the gels. Tensile tests suggested that glycerol addition affected the formability and malleability of the films, while α-CyD addition affected their formability and elongation properties. The addition of 10% glycerol and α-CyD did not affect the flexibility of the films, suggesting that the malleability and strength were impacted. Soft capsules could not be prepared by adding only glycerol or α-CyD to Sangelose. Soft capsules with favorable disintegration behavior were obtained upon adding α-CyD to gels along with 10% glycerol. Sangelose combined with a suitable amount of glycerol and α-CyD has preferable characteristics for film formation and may have potential applications in the pharmaceutical and health food sectors.
(キーワード): Glycerol / Tensile Strength / Gelatin / Carrageenan / alpha-Cyclodextrins / Gels
(出版サイトへのリンク): ● Publication site (DOI): 10.1080/03639045.2023.2182127
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 36803493; ● Summary page in Scopus @ Elsevier: 2-s2.0-85149478380

(DOI: 10.1080/03639045.2023.2182127, PubMed: 36803493, Elsevier: Scopus) Sorato Ikeda, Masanori Kobayashi, Soken Aoki, Takayuki Terukina, Takanori KANAZAWA, Hiroyuki Kojima and Hiromu Kondo :
3D-Printed Fast-Dissolving Oral Dosage Forms via Fused Deposition Modeling Based on Sugar Alcohol and Poly(Vinyl Alcohol)-Preparation, Drug Release Studies and In Vivo Oral Absorption.,
Pharmaceutics, Vol.15, No.2, 395, 2023.

(要約): Three-dimensional printing technology holds marked promise for the pharmaceutical industry and is now under intense investigation. Most research is aimed at a greater efficiency in printing oral dosage forms using powder bed printing or fused deposition modeling (FDM). Oral dosage forms printed by FDM tend to be hard objects, which reduce the risk of cracking and chipping. However, one challenge in printing oral dosage forms via FDM is achieving rapid drug release, because the materials for FDM are basically thermoplastic polymers with slow drug release properties. In this study, we investigated printing a fast-dissolving oral dosage form by adding sugar alcohol to a poly(vinyl alcohol)-based formulation for FDM. Filaments which contain sugar alcohol were successfully prepared, and objects were printed with them as oral dosage forms by FDM. On drug release testing, a printed oral dosage form in a ring shape which contained 55% maltitol showed a more than 85% drug release in 15 min. In vivo oral absorption of this printed oral dosage form in dogs was comparable to that of a conventional fast-dissolving tablet. Of particular interest, the drug release profile and drug amount of the oral dosage forms can be easily controlled by a change in shape using 3D Computer Aided Design. These characteristics will encourage the prevalence of FDM by the pharmaceutical industry, and contribute to the promotion of personalized medicine.
(出版サイトへのリンク): ● Publication site (DOI): 10.3390/pharmaceutics15020395
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 36839717; ● Summary page in Scopus @ Elsevier: 2-s2.0-85149104841

(DOI: 10.3390/pharmaceutics15020395, PubMed: 36839717, Elsevier: Scopus) Ryota Kimata, Naoki Yoshihara, Takayuki Terukina, Takanori KANAZAWA and Hiromu Kondo :
Impact of Properties of Hydrated Silicon Dioxide as Core Material on the Characteristics of Drug-containing Particles Prepared by the 2-step Process Melt Granulation Technology, MALCORE.,
AAPS PharmSciTech, Vol.24, No.1, 28, 2022.

(要約): Drug-containing particles (DCPs) are frequently used as cores in the development of solid oral dosage forms. The wet layering technique, which is a typical approach for preparing DCPs, requires the use of solvents and a long manufacturing time. In our previous study, we developed a novel manufacturing technology, MALCORE, which can solve these problems through melt granulation. However, particle size control methods for DCPs in MALCORE and the effect of the physical properties of the hydrated silicon dioxide (HSD) used for the core have not been clarified. The aim of this study was to examine the effects of the particle and pore sizes of HSD on the properties of the prepared DCPs. The results showed that the DCPs prepared using MALCORE could be controlled by the particle size of HSD. The drug-loading efficiency tended to decrease as HSD particle size increased. Additionally, the amount of drug layering in DCPs increased as the pore size of HSD increased, but HSDs with a pore size much larger than the particle size were not able to properly layer the drug. These findings are helpful for applying MALCORE to a variety of oral drug formulations.
(キーワード): Drug Compounding / Freezing / 技術 (technology) / Excipients / Silicon Dioxide / Particle Size / Tablets
(出版サイトへのリンク): ● Publication site (DOI): 10.1208/s12249-022-02492-6
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 36577811; ● Summary page in Scopus @ Elsevier: 2-s2.0-85145084174

(DOI: 10.1208/s12249-022-02492-6, PubMed: 36577811, Elsevier: Scopus) Takumi Kurano, Takanori KANAZAWA, Shingo Iioka, Hiromu Kondo, Yasuhiro Kosuge and Toyofumi Suzuki :
Intranasal Administration of N-acetyl-L-cysteine Combined with Cell-Penetrating Peptide-Modified Polymer Nanomicelles as a Potential Therapeutic Approach for Amyotrophic Lateral Sclerosis.,
Pharmaceutics, Vol.14, No.12, 2590, 2022.

(要約): Intranasal administration is a promising route for direct drug delivery to the brain; its combination with nanocarriers enhances delivery. We have previously shown that intranasal administration combined with PEG-PCL-Tat (a nanocarrier) efficiently delivers drugs to the brain and exhibits excellent therapeutic efficacy against brain diseases. We aimed to clarify whether intranasal administration combined with PEG-PCL-Tat represents a useful drug delivery system (DDS) for amyotrophic lateral sclerosis (ALS) pharmacotherapy. We used -acetyl-L-cysteine (NAC) as a model drug with low transferability to the spinal cord and determined the physicochemical properties of NAC/PEG-PCL-Tat. After intranasal administration of NAC/PEG-PCL-Tat, we measured the survival duration of superoxide dismutase-1 G93A mutant transgenic mice (G93A mice), widely used in ALS studies, and quantitatively analyzed the tissue distribution of NAC/PEG-PCL-Tat in ddY mice. The mean particle size and zeta potential of NAC/PEG-PCL-Tat were 294 nm and + 9.29 mV, respectively. Treatment with repeated intranasal administration of NAC/PEG-PCL-Tat considerably prolonged the median survival of G93A mice by 11.5 days compared with that of untreated G93A mice. Moreover, the highest distribution after a single administration of NAC/PEG-PCL-Tat was measured in the spinal cord. These results suggest that intranasal administration combined with PEG-PCL-Tat might represent a useful DDS for ALS therapeutics.
(出版サイトへのリンク): ● Publication site (DOI): 10.3390/pharmaceutics14122590
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 36559085; ● Summary page in Scopus @ Elsevier: 2-s2.0-85144725170

(DOI: 10.3390/pharmaceutics14122590, PubMed: 36559085, Elsevier: Scopus) Momoka Yamaguchi, Takanori KANAZAWA, Sumire Morino, Shingo Iioka, Yuta Watanabe, Naoki Dohi, Kenjirou Higashi, Hiromu Kondo and Tomohisa Ishikawa :
Increased Tropism of Extracellular Vesicles Derived from Palmitic Acid-Treated Hepatocytes to Activated Hepatic Stellate Cells.,
Membranes, Vol.12, No.10, 1023, 2022.

(要約): Myofibroblast-like activated hepatic stellate cells (aHSCs), which produce collagen, a major cause of liver fibrosis, are specific target cells for antifibrotic treatment. Recently, several reports have indicated that extracellular vesicles (EVs) play important roles in cell-to-cell communication through their tropism for specific cells or organs. Therefore, the present study aimed to identify aHSC-directed EVs by focusing on cell-to-cell interactions in the liver under pathological conditions. EVs were derived from the hepatocyte cell line AML12 treated with or without palmitic acid (PA) and evaluated for their physical properties and uptake by the aHSC cell line LX-2. AML12-derived EVs had a mean particle diameter of 110-130 nm, negative charge, and expressed the exosomal makers CD9 and CD63. PA-treated AML12 cells released larger EVs with higher protein levels than those without PA treatment. The intracellular uptake efficacy of EVs derived from PA-treated AML12 cells into activated LX-2 cells was significantly higher than those without PA treatment. Our study revealed that PA treatment induces hepatocytes to release EVs with aHSC-tropism. These findings may contribute to the development of an EV-based drug delivery system (DDS) for aHSC-targeted therapy and provide new insights into the role of steatotic hepatocyte-derived EVs in physiological or pathophysiological functions.
(出版サイトへのリンク): ● Publication site (DOI): 10.3390/membranes12101023
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 36295784; ● Summary page in Scopus @ Elsevier: 2-s2.0-85140877006

(DOI: 10.3390/membranes12101023, PubMed: 36295784, Elsevier: Scopus) Hisako Ibaraki, Naruhiro Hatakeyama, Akihiro Takeda, Naoki Arima and Takanori KANAZAWA :
Multifunctional peptide carrier-modified polymer micelle accelerates oral siRNA-delivery to the colon and improves gene silencing-mediated therapeutic effects in ulcerative colitis,
Journal of Drug Delivery Science and Technology, Vol.73, 103481, 2022.

(出版サイトへのリンク): ● Publication site (DOI): 10.1016/j.jddst.2022.103481
(文献検索サイトへのリンク): ● Summary page in Scopus @ Elsevier: 2-s2.0-85131434167

(DOI: 10.1016/j.jddst.2022.103481, Elsevier: Scopus) Takayuki Terukina, Yoshiki Uchiyama, Fumiya Kikuma, Saki Fukumitsu, Nana Iwata, Takanori KANAZAWA and Hiromu Kondo :
A New Approach for Characterizing the Thixotropic Properties of Gel Formulations as Sprayable Agents Based on Rheological Analysis.,
AAPS PharmSciTech, Vol.23, No.5, 119, 2022.

(要約): The present study evaluated the rheological properties of gel formulations composed of the thixotropic peptide amphiphile, palmitoyl-glycine-histidine (Pal-GH), and the thickener, propylene glycol alginate (PGA), to propose a proper approach to design sprayable gel formulations with good spray performance and high retention of a therapeutic agent. The hysteresis loop area (HLA), a conventional index of thixotropy, was determined from the relationship between the shear stress and shear rate of various formulations with different amounts of Pal-GH and PGA. In addition, a new assessment method for characterizing the thixotropy using the initial structure recovery speed was determined based on the time course of the complex modulus (G*) after structural breakdown of the gel formulations. The G* values increased with the increase in the amount of Pal-GH and PGA, indicating that the formulations were not deformable. Additionally, high HLA and high initial structure recovery speed are preferable when selecting a formulation with good spray performance and high retention. As suitable combinations of Pal-GH and PGA could exhibit both high HLA and high initial structure recovery speed, they are promising components for gel formulations to be used as sprayable agents with good spray performance and high retention. The results also suggested that the initial structure recovery speed would reflect the thixotropy for the formulation more appropriately than HLA. Thus, the initial structure recovery speed could be a useful scale for the preparation of sprayable gel formulations.
(キーワード): レオロジー (rheology) / Viscosity / Gels / Alginates
(出版サイトへのリンク): ● Publication site (DOI): 10.1208/s12249-022-02276-y
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 35449239; ● Summary page in Scopus @ Elsevier: 2-s2.0-85128692580

(DOI: 10.1208/s12249-022-02276-y, PubMed: 35449239, Elsevier: Scopus) Yusuke Oe, Shinichi Ogino, Masanori Kobayashi, Hiroyuki Kojima, Takayuki Terukina, Takanori KANAZAWA and Hiromu Kondo :
Testosterone Sustained Release Microspheres for the Treatment of Fecal Incontinence.,
Journal of Pharmaceutical Sciences, Vol.111, No.8, 2322-2329, 2022.

(要約): The objective of this study was to develop a testosterone sustained release formulation for the treatment of fecal incontinence. To suppress the initial burst release of testosterone, which can lead to systemic toxicity, we incorporated a washing step using an aminoalkyl methacrylate copolymer E solution or propylene glycol solution into a typical o/w emulsion method to prepare polylactic-co-glycolic acid microspheres. We used this method to develop a polylactic-co-glycolic acid microsphere formulation that shows sustained release of testosterone for up to one month. Not only did this formulation show a sustained release profile after administration into the intersphincteric groove in minipigs, it also increased both the anal pressure and mass of the external anal sphincter, while keeping systemic testosterone exposure low. Thus, this formulation successfully affected both the internal and external anal sphincters with a sufficient safety profile, deeming it a promising candidate treatment strategy for fecal incontinence.
(キーワード): Animals / Delayed-Action Preparations / Fecal Incontinence / Lactic Acid / Microspheres / Particle Size / Polyglycolic Acid / Polylactic Acid-Polyglycolic Acid Copolymer / Swine / Swine, Miniature / Testosterone
(出版サイトへのリンク): ● Publication site (DOI): 10.1016/j.xphs.2022.03.008
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 35314188; ● Summary page in Scopus @ Elsevier: 2-s2.0-85127465907

(DOI: 10.1016/j.xphs.2022.03.008, PubMed: 35314188, Elsevier: Scopus) Takumi Kurano, Takanori KANAZAWA, Aoi Ooba, Yudai Masuyama, Nao Maruhana, Mayu Yamada, Shingo Iioka, Hisako Ibaraki, Yasuhiro Kosuge, Hiromu Kondo and Toyofumi Suzuki :
Nose-to-brain/spinal cord delivery kinetics of liposomes with different surface properties.,
Journal of Controlled Release, Vol.344, 225-234, 2022.

(要約): The administration of liposomes via nose-to-brain delivery is expected to become a strategy for efficient drug delivery to the central nervous system. Efficient nose-to-brain delivery and the kinetics of drugs administered in this manner depend on the properties of liposomes. However, there is a lack of basic knowledge of which liposomes are suitable for this purpose. Here, a qualitative study of intranasally administered liposomes (positively charged, neutral, and negatively charged, with or without polyethylene glycol [PEG] modification; particle size <100 nm) was performed to elucidate their dynamics in the brain and spinal cord. Additionally, a quantitative investigation was performed to ascertain their distribution in each part of the brain and spinal cord. The effects of liposome surface charge and PEG modification on the kinetics and distribution post intranasal administration were investigated via two experiments. Qualitative evaluation was performed via ex vivo observation after intranasal administration of fluorescently labeled liposomes. Neutral PEG-modified liposomes were distributed throughout the brain and spinal cord 60 min after administration, and the fluorescence intensity increased with time. By contrast, non-PEG-modified neutral liposomes showed particularly strong fluorescence in the olfactory bulb, and the fluorescence was localized in the anterior part of the brain. Positively charged liposomes showed low fluorescence around the lateral part of the brain and lumbar spinal cord 60 min after administration. Low fluorescence was observed in the whole brain and spinal cord, with strong fluorescence being observed in the olfactory bulb after 120 min of administration. Negatively charged liposomes showed no fluorescence at 60 min after administration, but low fluorescence was observed throughout the brain and spinal cord 120 min after administration. We quantified the radioactivity in the brain and spinal cord after intranasal administration of radioisotope-labeled liposomes. Neutral liposomes showed the highest distribution by area under the drug concentration-time curve (AUC) in the brain and spinal cord compared to other liposomes. Compared with negatively charged liposomes, positively charged liposomes had a higher distribution in the olfactory bulb and forebrain, while negatively charged liposomes had a higher distribution in the hindbrain and bulbospinal tract cord. In addition, the distribution of PEG-modified neutral liposomes in the brain and spinal cord was significantly enhanced compared to that of non-PEG-modified neutral liposomes after 90 min of intranasal administration. These results indicate that surface charge and PEG modification strongly affect the efficiency of nose-to-brain delivery kinetics, and that PEG-modified neutral liposomes are excellent carriers for drug delivery to a wide area of the brain and spinal cord.
(キーワード): 脳 (brain) / Drug Delivery Systems / Kinetics / リポソーム (liposomes) / Polyethylene Glycols / 脊髄 (spinal cord) / 界面特性 (surface properties)
(出版サイトへのリンク): ● Publication site (DOI): 10.1016/j.jconrel.2022.03.017
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 35296406; ● Summary page in Scopus @ Elsevier: 2-s2.0-85126996547

(DOI: 10.1016/j.jconrel.2022.03.017, PubMed: 35296406, Elsevier: Scopus) Naoki Yoshihara, Ryota Kimata, Takayuki Terukina, Takanori KANAZAWA and Hiromu Kondo :
Novel preparation approach with a 2-step process for spherical particles with high drug loading and controlled size distribution using melt granulation: MALCORE®,
Advanced Powder Technology, Vol.33, No.2, 103409, 2022.

(出版サイトへのリンク): ● Publication site (DOI): 10.1016/j.apt.2021.103409
(文献検索サイトへのリンク): ● Summary page in Scopus @ Elsevier: 2-s2.0-85122020851

(DOI: 10.1016/j.apt.2021.103409, Elsevier: Scopus) Hisako Ibaraki, Naruhiro Hatakeyama, Naoki Arima, Akihiro Takeda, Yasuo Seta and Takanori KANAZAWA :
Systemic delivery of siRNA to the colon using peptide modified PEG-PCL polymer micelles for the treatment of ulcerative colitis.,
European Journal of Pharmaceutics and Biopharmaceutics, Vol.170, 170-178, 2022.

(要約): Ulcerative colitis (UC) is a refractory inflammatory bowel disease that causes inflammation and ulcers in the digestive tract, and significantly reduces the patient's quality of life. While existing UC treatments have many challenges, nanotechnology, and small interfering RNA (siRNA) based formulations are novel and promising for UC treatment. We previously reported that intravenous administration of MPEG-PCL-CH2R4H2C nanomicelles had high inflammatory site accumulation and remarkable therapeutic effects on rheumatoid arthritis by a phenomenon similar to enhanced permeability and retention effect. In this study, we investigated the effects of siRNA delivered using MPEG-PCL-CH2R4H2C nanomicelles through intravenous administration to the inflammation site of dextran sulfate sodium-induced colitis mice. The MPEG-PCL-CH2R4H2C micelles had optimum physical properties and high siRNA compaction ability. Moreover, model-siRNA delivered through MPEG-PCL-CH2R4H2C showed higher accumulation in the inflammatory site than that of the naked siRNA. Furthermore, intravenous administration of MPEG-PCL-CH2R4H2C/siRelA micelles, targeting siRelA, a subunit of NF-κB, significantly decreased the shortening of large intestine, clinical score, and production of inflammatory cytokines compared the 5-ASA and naked siRelA. These results suggest that MPEG-PCL-CH2R4H2C is a useful carrier for the systemic delivery and accumulation of siRNA, thus improving its therapeutic effect.
(キーワード): Administration, Intravenous / Animals / Cell-Penetrating Peptides / Colitis, Ulcerative / Disease Models, Animal / Mice / Mice, Inbred C57BL / Mice, Inbred DBA / Micelles / Polyesters / Polyethylene Glycols / Polymers / RNA, Small Interfering
(出版サイトへのリンク): ● Publication site (DOI): 10.1016/j.ejpb.2021.12.009
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 34963657; ● Search Scopus @ Elsevier (PMID): 34963657; ● Search Scopus @ Elsevier (DOI): 10.1016/j.ejpb.2021.12.009

(DOI: 10.1016/j.ejpb.2021.12.009, PubMed: 34963657) Takanori KANAZAWA, Yuki Hoashi, Hisako Ibaraki, Yuuki Takashima and Hiroaki Okada :
Electroporation-Based ex Vivo Gene Delivery into Dendritic Cells by Anionic Polymer-Coated Versatile Nuclear Localization Signal/pDNA Complex.,
Biological & Pharmaceutical Bulletin, Vol.44, No.12, 1866-1871, 2021.

(要約): In this study, we focused on a nuclear localization signal (NLS)-based versatile peptide vector, designed by us, combined with electroporation (EP) to establish an efficient gene delivery system to non-dividing or slow growing dendritic cells. We determined the intranuclear transport, gene expression, and cell viability in JAWS II mouse dendritic cells transfected with the green fluorescent protein (GFP) expression plasmid DNA alone (naked pEGFP); positive charged complex of NLS derivative STR-CH2SV40H2C, and pEGFP (binary complex); or negative charged complex of the binary complex with a biocompatible polyanion, γ-polyglutamic acid (ternary complex) combined with or without EP application. Although the binary complex showed higher nuclear transport and GFP expression in the absence of EP than those for naked pEGFP, the combination of EP significantly decreased the cell viability and did not improve the efficiency of compared gene expression. However, in the ternary complex, the intranuclear transport and GFP expression efficiency were significantly higher than those of naked pEGFP and the binary complex when combined with EP, and there was no decrease in cell viability. The results suggest that polyanion-coated ternary complex with EP is useful for non-viral gene delivery system into non-dividing cells for ex vivo gene/cell therapy.
(キーワード): Animals / Antigens, Polyomavirus Transforming / Cell Nucleus / Cell Survival / DNA (DNA) / Dendritic Cells / Electroporation / 遺伝子発現 (gene expression) / Gene Transfer Techniques / Genetic Therapy / Genetic Vectors / Green Fluorescent Proteins / 免疫療法 (immunotherapy) / Mice / Neoplasms / Nuclear Localization Signals / Oligopeptides / Plasmids / Polyglutamic Acid / Polymers / Transfection
(出版サイトへのリンク): ● Publication site (DOI): 10.1248/bpb.b21-00559
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 34853269; ● Summary page in Scopus @ Elsevier: 2-s2.0-85121666164

(DOI: 10.1248/bpb.b21-00559, PubMed: 34853269, Elsevier: Scopus) Takayuki Terukina, Taisei Takizawa, Shingo Iioka, Fuya Suzuki, Takanori KANAZAWA and Hiromu Kondo :
Characterization of the viscoelasticity of disintegrants by dynamic rheological analysis,
Powder Technology, Vol.392, 150-156, 2021.

(出版サイトへのリンク): ● Publication site (DOI): 10.1016/j.powtec.2021.07.009
(文献検索サイトへのリンク): ● Summary page in Scopus @ Elsevier: 2-s2.0-85109527153

(DOI: 10.1016/j.powtec.2021.07.009, Elsevier: Scopus) Noriyasu Kamei, Susumu Suwabe, Kenji Arime, Hidemi Bando, Kaho Murata, Maika Yamaguchi, Natsuki Yokoyama, Erina Tanaka, Ayaka Hashimoto, Takanori KANAZAWA, Yukio Ago and Mariko Takeda-Morishita :
Investigation of the Transport Pathways Associated with Enhanced Brain Delivery of Peptide Drugs by Intranasal Coadministration with Penetratin.,
Pharmaceutics, Vol.13, No.11, 1745, 2021.

(要約): We previously found that coadministering peptides and proteins with the cell-penetrating peptide L-penetratin intranasally significantly increased transport to the brain and enhanced pharmacological effects. The present study aimed to clarify the mechanisms of nose-to-brain drug delivery enhancement by L-penetratin coadministration. First, we compared the concentrations of Exendin-4 in plasma and brain after intranasal and subcutaneous administration and suggested that coadministration with L-penetratin facilitated the direct nose-to-brain transport of Exendin-4. Second, we demonstrated that L-penetratin did not stimulate the transport of Cy7-labeled Exendin-4 and insulin through the trigeminal nerves but shifted their distribution to the olfactory mucosal pathway. Third, we investigated the distribution of insulin into the deeper regions of the brain after delivery via the olfactory pathway and suggested that insulin had entered the olfactory bulb, bottom part of the brain, and perivascular space through the cerebrospinal fluid and had diffused throughout the brain. We further demonstrated that intranasally delivered insulin with L-penetratin specifically accumulated on the hippocampus neuronal cells. Thus, this study suggested that administrating peptide drugs intranasally with L-penetratin allows direct transport to the olfactory bulb, bottom part of the brain, and perivascular space of the cerebral artery. This technique also potentially allows targeting of specific brain areas.
(出版サイトへのリンク): ● Publication site (DOI): 10.3390/pharmaceutics13111745
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 34834159; ● Summary page in Scopus @ Elsevier: 2-s2.0-85117928078

(DOI: 10.3390/pharmaceutics13111745, PubMed: 34834159, Elsevier: Scopus) Mitsuyoshi Fukuda, Takanori KANAZAWA, Shingo Iioka, Takayuki Oguma, Ryohei Iwasa, Saki Masuoka, Naoto Suzuki, Yasuhiro Kosuge and Toyofumi Suzuki :
Quantitative analysis of inulin distribution in the brain focused on nose-to-brain route via olfactory epithelium by reverse esophageal cannulation.,
Journal of Controlled Release, Vol.332, 493-501, 2021.

(要約): This study aimed to determine the effect of intranasal dosing speed and administrating volume of nose-to-brain delivery on candidates for peptide drugs (molecular weight ca. 1-10 kDa). Using inulin as the model molecule of a peptide drug, intranasal administration by cannulation from the airway side through the esophagus was tested in mice. This was done to determine the quantitative distribution levels of the drug in the brain and cerebral spinal fluid (CSF). Distribution levels were increased with slower and constant speed (5 μL/min), with higher dosing volume equivalent to nasal volume per body weight in mice (25 μL), and were recorded 0.27% injected dose per gram of tissue (ID/g) in the brain, and 0.24% injected dose per milliliter (ID/mL) in the CSF at 60 min. Then, brain distribution resulting from reverse cannulation was two times more than that of the typical intranasal administration method using a micropipette. In addition, the percentage of inulin estimated to reach the brain via direct transport (%DTP) during reverse cannulation was estimated to be 93%, suggesting that ~95% of the total dose was transferred directly to the brain via the olfactory mucosa. These results show that distribution of the peptide drug in the brain was increased through constant administration at a slow and constant speed.
(キーワード): Administration, Intranasal / Animals / 脳 (brain) / Catheterization / Drug Delivery Systems / Esophagus / Inulin / Mice / Nasal Mucosa / Olfactory Mucosa / Rats / Rats, Sprague-Dawley
(出版サイトへのリンク): ● Publication site (DOI): 10.1016/j.jconrel.2021.02.024
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 33647429; ● Summary page in Scopus @ Elsevier: 2-s2.0-85102572153

(DOI: 10.1016/j.jconrel.2021.02.024, PubMed: 33647429, Elsevier: Scopus) Hisako Ibaraki, Akihiro Takeda, Naoki Arima, Naruhiro Hatakeyama, Yuuki Takashima, Yasuo Seta and Takanori KANAZAWA :
In Vivo Fluorescence Imaging of Passive Inflammation Site Accumulation of Liposomes via Intravenous Administration Focused on Their Surface Charge and PEG Modification.,
Pharmaceutics, Vol.13, No.104, 2021.

(要約): Nanocarriers such as liposomes have been attracting attention as novel therapeutic methods for inflammatory autoimmune diseases such as rheumatoid arthritis and ulcerative colitis. The physicochemical properties of intravenously administered nanomedicines enable them to target inflamed tissues passively. However, few studies have attempted to determine the influences of nanoparticle surface characteristics on inflammation site accumulation. Here, we aimed to study the effects of polyethylene glycol (PEG) modification and surface charge on liposome ability to accumulate in inflammatory sites and be uptake by macrophages. Four different liposome samples with different PEG modification and surface charge were prepared. Liposome accumulation in the inflammation sites of arthritis and ulcerative colitis model mice was evaluated by using in vivo imaging. There was greater PEG-modified than unmodified liposome accumulation at all inflammation sites. There was greater anionic than cationic liposome accumulation at all inflammation sites. The order in which inflammation site accumulation was confirmed was PEG-anionic > PEG-cationic > anionic > cationic. PEG-anionic liposomes had ~2.5× higher fluorescence intensity than PEG-cationic liposomes, and the PEG-liposomes had ~2× higher fluorescence intensity than non-PEG liposomes. All liposomes have not accumulated at the inflammation sites in healthy mice. Furthermore, cationic liposomes were taken up to ~10× greater extent by RAW264.7 murine macrophages. Thus, PEG-cationic liposomes that have the ability to accumulate in inflammatory sites via intravenous administration and to be taken up by macrophages could be useful.
(出版サイトへのリンク): ● Publication site (DOI): 10.3390/pharmaceutics13010104
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 33466905; ● Summary page in Scopus @ Elsevier: 2-s2.0-85099762757

(DOI: 10.3390/pharmaceutics13010104, PubMed: 33466905, Elsevier: Scopus) Misako Kawai, Hisako Ibaraki, Yuuki Takashima, Takanori KANAZAWA and Hiroaki Okada :
Development of a Liquid Crystal Formulation that Can Penetrate the Stratum Corneum for Intradermal Delivery of Small Interfering RNA.,
Molecular Pharmaceutics, Vol.18, No.3, 1038-1047, 2021.

(要約): Topical delivery of small interfering RNA (siRNA) can be an attractive method for the treatment of skin diseases and improving the quality of life of patients. However, it is difficult for siRNA to pass through the two major barriers of the skin: the stratum corneum (SC) and tight junctions. We have previously reported that atopic dermatitis of skin without the SC can be efficiently treated by the intradermal administration of trans-activator of transcription (Tat) peptide and AT1002 (tight junction opening peptide). However, novel drug delivery systems are needed for effective SC penetration. Therefore, in the present study, we aimed to develop a lyotropic liquid crystalline (LC) system containing Tat and AT1002 for effective siRNA penetration through the SC. An LC formulation was prepared using selachyl alcohol and purified water, and its skin penetration ability was evaluated. No fluorescence was observed in mouse skin treated with a siRNA solution, as there was no intradermal localization of siRNA from naked siRNA. However, intradermal delivery of siRNA was remarkable and extensive with the LC formulation containing both Tat and AT1002. Semiquantitative analysis by brightness measurement revealed that the LC formulation containing both Tat and AT1002 had significantly enhanced intact skin permeability than other formulations. These results show that the functional peptides in the LC formulation increased SC penetration and intradermal delivery in the healthy skin. Therefore, this novel LC system may be useful in the treatment of various skin diseases.
(キーワード): Animals / Dermatitis, Atopic / Drug Delivery Systems / Epidermis / Liquid Crystals / 男性 (male) / Mice / Mice, Inbred ICR / Oligopeptides / Peptides / Permeability / 生活の質 (quality of life) / RNA, Small Interfering / 皮膚 (skin) / Skin Absorption / Tight Junctions
(出版サイトへのリンク): ● Publication site (DOI): 10.1021/acs.molpharmaceut.0c00997
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 33395310; ● Summary page in Scopus @ Elsevier: 2-s2.0-85099645396

(DOI: 10.1021/acs.molpharmaceut.0c00997, PubMed: 33395310, Elsevier: Scopus) 鈴木豊史, 藏野匠, 金沢貴憲, 鈴木直人 :
動的接触角及びサーモグラフィックアプローチを組み合わせた水浸透速度の新規評価法の確立:口腔内崩壊錠における崩壊特性の重要性,
薬学雑誌, Vol.140, No.8, 1071-1080, 2020年.

(キーワード): orally disintegrating tablet / disintegration time / OD-mate / water penetration rate / dynamic contact angle / infrared thermography
(出版サイトへのリンク): ● Publication site (DOI): 10.1248/yakushi.20-00072
(文献検索サイトへのリンク): ● CiNii @ 国立情報学研究所 (CRID): 1390848250133276288; ● Search Scopus @ Elsevier (DOI): 10.1248/yakushi.20-00072

(DOI: 10.1248/yakushi.20-00072, CiNii: 1390848250133276288) Hisako Ibaraki, Takanori KANAZAWA, Wan-Yi Chien, Hidemasa Nakaminami, Masakazu Aoki, Kosuke Ozawa, Hiroshi Kaneko, Yuuki Takashima, Norihisa Noguchi and Yasuo Seta :
The effects of surface properties of liposomes on their activity against Pseudomonas aeruginosa PAO-1 biofilm,
Journal of Drug Delivery Science and Technology, Vol.57, 101754, 2020.

(出版サイトへのリンク): ● Publication site (DOI): 10.1016/j.jddst.2020.101754
(文献検索サイトへのリンク): ● Search Scopus @ Elsevier (DOI): 10.1016/j.jddst.2020.101754

(DOI: 10.1016/j.jddst.2020.101754) Takanori KANAZAWA, Hiroyuki Taki and Hiroaki Okada :
Nose-to-brain drug delivery system with ligand/cell-penetrating peptide-modified polymeric nano-micelles for intracerebral gliomas.,
European Journal of Pharmaceutics and Biopharmaceutics, Vol.152, 85-94, 2020.

(要約): We previously developed a nose-to-brain delivery system using poly(ethylene glycol)-polycaprolactone block polymeric micelles modified by a cell-penetrating peptide, Tat (PEG-PCL-Tat). This system showed excellent delivery of the anti-cancer drug camptothecin to the brain and improved therapeutic efficacy in a brain tumor model. However, improvements are necessary to selectively deliver drugs to tumor sites once they enter the brain, and avoid toxic side effects to normal brain tissue. In this study, to develop tumor-selective novel polymeric micelles, mixed micelles consisting of Tat-conjugated polymer micelles and stearoyl-modified bombesin (Bom/PEG-PCL-Tat) were designed. The GRPR selectivity, cellular uptake, and cytotoxicity in C6 glioma cells as well as the intracerebral drug distribution and therapeutic efficacy of Bom/PEG-PCL-Tat mixed micelles after intranasal administration in C6 glioma orthotropic grafted rats were evaluated. Selective cellular uptake and marked cytotoxic effects against GRPR-expressing C6 glioma cells were observed, as well as C6 tumor tissue-specific accumulation in vivo. Rats treated with camptothecin subsequent to a brain tumor graft survived longer when the drug was delivered by Bom/PEG-PCL-Tat mixed micelles than by PEG-PCL-Tat micelles.
(キーワード): Administration, Intranasal / Animals / Antineoplastic Agents / Bombesin / 脳 (brain) / Brain Neoplasms / Camptothecin / Cell Line, Tumor / Cell-Penetrating Peptides / Drug Carriers / Glioma / Ligands / 男性 (male) / Micelles / ナノ粒子 (nanoparticles) / Nose / Particle Size / Polyesters / Polyethylene Glycols / Polymers / Rats / Rats, Sprague-Dawley
(出版サイトへのリンク): ● Publication site (DOI): 10.1016/j.ejpb.2020.05.001
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 32387702; ● Summary page in Scopus @ Elsevier: 2-s2.0-85084435992

(DOI: 10.1016/j.ejpb.2020.05.001, PubMed: 32387702, Elsevier: Scopus) Hiroshi Nango, Yasuhiro Kosuge, Nana Yoshimura, Hiroko Miyagishi, Takanori KANAZAWA, Kaname Hashizaki, Toyofumi Suzuki and Kumiko Ishige :
The Molecular Mechanisms Underlying Prostaglandin D-Induced Neuritogenesis in Motor Neuron-Like NSC-34 Cells.,
Cells, Vol.9, No.946, 2020.

(要約): Prostaglandins are a group of physiologically active lipid compounds derived from arachidonic acid. Our previous study has found that prostaglandin E promotes neurite outgrowth in NSC-34 cells, which are a model for motor neuron development. However, the effects of other prostaglandins on neuronal differentiation are poorly understood. The present study investigated the effect of prostaglandin D (PGD) on neuritogenesis in NSC-34 cells. Exposure to PGD resulted in increased percentages of neurite-bearing cells and neurite length. Although D-prostanoid receptor (DP) 1 and DP2 were dominantly expressed in the cells, BW245C (a DP1 agonist) and 15(R)-15-methyl PGD (a DP2 agonist) had no effect on neurite outgrowth. Enzyme-linked immunosorbent assay demonstrated that PGD was converted to 15-deoxy-Δ-prostaglandin J (15d-PGJ) under cell-free conditions. Exogenously applied 15d-PGJ mimicked the effect of PGD on neurite outgrowth. GW9662, a peroxisome proliferator-activated receptor-gamma (PPARγ) antagonist, suppressed PGD-induced neurite outgrowth. Moreover, PGD and 15d-PGJ increased the protein expression of Islet-1 (the earliest marker of developing motor neurons), and these increases were suppressed by co-treatment with GW9662. These results suggest that PGD induces neuritogenesis in NSC-34 cells and that PGD-induced neurite outgrowth was mediated by the activation of PPARγ through the metabolite 15d-PGJ.
(キーワード): Humans / Motor Neurons / Neurites / Prostaglandin D2
(出版サイトへのリンク): ● Publication site (DOI): 10.3390/cells9040934
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 32290308; ● Summary page in Scopus @ Elsevier: 2-s2.0-85083411172

(DOI: 10.3390/cells9040934, PubMed: 32290308, Elsevier: Scopus) Hisako Ibaraki, Takanori KANAZAWA, Minami Owada, Keiko Iwaya, Yuuki Takashima and Yasuo Seta :
Anti-Metastatic Effects on Melanoma via Intravenous Administration of Anti-NF-κB siRNA Complexed with Functional Peptide-Modified Nano-Micelles.,
Pharmaceutics, Vol.12, No.1, 64, 2020.

(要約): Controlling metastasis is an important strategy in cancer treatment. Nanotechnology and nucleic acids with novel modalities are promising regulators of cancer metastasis. We aimed to develop a small interfering RNA (siRNA) systemic delivery and anti-metastasis system using nanotechnology. We previously reported that polyethylene glycol-polycaprolactone (PEG-PCL) and functional peptide CH2R4H2C nano-micelle (MPEG-PCL-CH2R4H2C) has high siRNA silencing effects, indicated by increased drug accumulation in tumor-bearing mice, and has an anti-tumor effect on solid tumors upon systemic injection. In this study, we aimed to apply our micelles to inhibit metastasis and evaluated the inhibitory effect of anti-RelA siRNA (siRelA), which is a subunit of NF-κB conjugated with MPEG-PCL-CH2R4H2C, via systemic administration. We report that siRelA/MPEG-PCL-CH2R4H2C had a high cellular uptake and suppressed the migration/invasion of cells in B16F10 cells without toxicity. In addition, in a lung metastasis mouse model using intravenous administration of B16F10 cells treated with siRelA/MPEG-PCL-CH2R4H2C, the number of lung nodules in lung tissue significantly decreased compared to naked siRelA and siControl/MPEG-PCL-CH2R4H2C micelle treatments. Hence, we show that RelA expression can reduce cancer metastasis, and MPEG-PCL-CH2R4H2C is an effective siRNA carrier for anti-metastasis cancer therapies.
(出版サイトへのリンク): ● Publication site (DOI): 10.3390/pharmaceutics12010064
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 31952106; ● Search Scopus @ Elsevier (PMID): 31952106; ● Search Scopus @ Elsevier (DOI): 10.3390/pharmaceutics12010064

(DOI: 10.3390/pharmaceutics12010064, PubMed: 31952106) Naoto Suzuki, Takanori KANAZAWA, Kazuhiko Takatori, Toyofumi Suzuki and Toshiro Fukami :
Crystal Structure Analysis and Pharmaceutical Properties of Amide Salts Consisting of Paracetamol/Sulfonic Acids as Solid Forms Prepared by Grinding,
Crystal Growth & Design, Vol.20, 590-599, 2020.

(出版サイトへのリンク): ● Publication site (DOI): 10.1021/acs.cgd.9b00763
(文献検索サイトへのリンク): ● Search Scopus @ Elsevier (DOI): 10.1021/acs.cgd.9b00763

(DOI: 10.1021/acs.cgd.9b00763) Takanori KANAZAWA, Takumi Kurano, Hisako Ibaraki, Yuuki Takashima, Toyofumi Suzuki and Yasuo Seta :
Therapeutic Effects in a Transient Middle Cerebral Artery Occlusion Rat Model by Nose-To-Brain Delivery of Anti-TNF-Alpha siRNA with Cell-Penetrating Peptide-Modified Polymer Micelles.,
Pharmaceutics, Vol.11, No.9, 478, 2019.

(要約): We previously reported that siRNA delivery to the brain is improved by the nose-to-brain delivery route and by conjugation with polyethylene glycol-polycaprolactone (PEG-PCL) polymer micelles and the cell-penetrating peptide, Tat (PEG-PCL-Tat). In this study, we evaluated the nose-to-brain delivery of siRNA targeting TNF-α (siTNF-α) conjugated with PEG-PCL-Tat to investigate its therapeutic effects on a transient middle cerebral artery occlusion (t-MCAO) rat model of cerebral ischemia-reperfusion injury. Intranasal treatment was provided 30 min after infarction induced via suturing. Two hours after infarction induction, the suture was removed, and blood flow was released. At 22 h post-reperfusion, we assessed the infarcted area, TNF-α production, and neurological score to determine the therapeutic effects. The infarcted area was observed over a wide range in the untreated group, whereas shrinkage of the infarcted area was observed in rats subjected to intranasal administration of siTNF-α with PEG-PCL-Tat micelles. Moreover, TNF-α production and neurological score in rats treated by intranasal administration of siTNF-α with PEG-PCL-Tat micelles were significantly lower than those in untreated and naked siTNF-α-treated rats. These results indicate that nose-to-brain delivery of siTNF-α conjugated with PEG-PCL-Tat micelles alleviated the symptoms of cerebral ischemia-reperfusion injury.
(出版サイトへのリンク): ● Publication site (DOI): 10.3390/pharmaceutics11090478
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 31540164; ● Summary page in Scopus @ Elsevier: 2-s2.0-85074561408

(DOI: 10.3390/pharmaceutics11090478, PubMed: 31540164, Elsevier: Scopus) Hisako Ibaraki, Takanori KANAZAWA, Chihiro Oogi, Yuuki Takashima and Yasuo Seta :
Effects of surface charge and flexibility of liposomes on dermal drug delivery,
Journal of Drug Delivery Science and Technology, Vol.50, 155-162, 2019.

(出版サイトへのリンク): ● Publication site (DOI): 10.1016/j.jddst.2019.01.028
(文献検索サイトへのリンク): ● Summary page in Scopus @ Elsevier: 2-s2.0-85060331181

(DOI: 10.1016/j.jddst.2019.01.028, Elsevier: Scopus) 福田春香, 鈴木豊史, 橋崎要, 吉村彩也香, 小林千翔, 重谷美子, 鈴木直人, 金沢貴憲, 深水啓朗, 山本佳久 :
小児用粉状製剤を服用するためのペースト状態に必要な最適水量:降伏値に基づいた考察と後発医薬品への適用,
薬学雑誌, Vol.139, No.2, 299-308, 2019年.

(キーワード): pediatric powder / paste state / yield value / spread meter / generic medicine
(出版サイトへのリンク): ● Publication site (DOI): 10.1248/yakushi.18-00182
(文献検索サイトへのリンク): ● CiNii @ 国立情報学研究所 (CRID): 1390564238074535936; ● Search Scopus @ Elsevier (DOI): 10.1248/yakushi.18-00182

(DOI: 10.1248/yakushi.18-00182, CiNii: 1390564238074535936) Hisako Ibaraki, Takanori KANAZAWA, Takumi Kurano, Chihiro Oogi, Yuuki Takashima and Yasuo Seta :
Anti-RelA siRNA-Encapsulated Flexible Liposome with Tight Junction-Opening Peptide as a Non-invasive Topical Therapeutic for Atopic Dermatitis.,
Biological & Pharmaceutical Bulletin, Vol.42, No.7, 1216-1225, 2019.

(要約): Small interfering RNA (siRNA) has been proposed as a novel treatment for atopic dermatitis (AD) because it suppresses sequence-specific mRNA expression. Indeed siRNA-based therapy achieves an almost complete cure with fewer side effects than currently available treatments. However, the tight junctions in the granular layer of the epidermis in the atopic skin are barriers to siRNA delivery. We previously reported the potential clinical utility of AT1002, a peptide that opens tight junctions. In the present study, we evaluated a topical siRNA-based therapy for AD using AT1002 in combination with a flexible liposome. The 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE)/cholesteryl hemisuccinate (CHEMS) liposome was chosen as a carrier for siRNA because of its highly flexible structure and permeability. We prepared siRNA-encapsulated DOPE/CHEMS liposomes and examined their physical properties, safety, uptake into RAW264.7 cells, and topical application in healthy and AD-affected skin. We then assessed the efficacy of anti-nuclear factor-kappa B (NF-κB) (RelA) siRNA (siRelA)-encapsulated DOPE/CHEMS liposomes with AT1002 in AD model mice. The siRNA-DOPE/CHEMS liposomes were absorbed significantly better than siRNA alone and they enhanced siRNA skin penetration without toxicity. Moreover, siRelA-DOPE/CHEMS liposomes with AT1002 alleviated AD symptoms and reduced the levels of inflammatory cytokines in AD model mice. Therefore, the combination of AT1002 and DOPE/CHEMS liposomes could be a dermally applied RNA interference therapeutic system for effective RNA delivery and AD treatment.
(キーワード): Administration, Topical / Animals / Cell Survival / Cholesterol Esters / Dermatitis, Atopic / リポソーム (liposomes) / 男性 (male) / Mice / Mice, Inbred C57BL / Oligopeptides / Phosphatidylethanolamines / RAW 264.7 Cells / RNA Interference / RNA, Small Interfering / 皮膚 (skin) / Tight Junctions / Transcription Factor RelA
(出版サイトへのリンク): ● Publication site (DOI): 10.1248/bpb.b19-00259
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 31257297; ● Summary page in Scopus @ Elsevier: 2-s2.0-85068559507

(DOI: 10.1248/bpb.b19-00259, PubMed: 31257297, Elsevier: Scopus) Takanori KANAZAWA, Mitsuyoshi Fukuda, Naoto Suzuki and Toyofumi Suzuki :
Novel Methods for Intranasal Administration Under Inhalation Anesthesia to Evaluate Nose-to-Brain Drug Delivery.,
Journal of visualized experiments : JoVE, No.141, e58485, 2018.

(要約): Intranasal administration has been reported to be a potential pathway for nose-to-brain delivery of therapeutic agents that circumvents the blood-brain barrier. However, there have been few reports regarding not only the quantitative analysis but also optimal administration conditions and dosing regimens for investigations of nose-to-brain delivery. The limited progress in research on nose-to-brain pathway mechanisms using rodents represents a significant impediment in terms of designing nose-to-brain delivery systems for candidate drugs. To gain some headway in this regard, we developed and evaluated two novel methods of stable intranasal administration under inhalation anesthesia for experimental animals. We also describe a method for the evaluation of drug distribution levels in the brain via the nose-to-brain pathway using radio-labeled [C]-inulin (molecular weight: 5,000) as a model substrate of water-soluble macromolecules. Initially, we developed a pipette-based intranasal administration protocol using temporarily openable masks, which enabled us to perform reliable administration to animals under stable anesthesia. Using this system, [C]-inulin could be delivered to the brain with little experimental error. We subsequently developed an intranasal administration protocol entailing reverse cannulation from the airway side through the esophagus, which was developed to minimize the effects of mucociliary clearance (MC). This technique led to significantly higher levels of [C]-inulin, which was quantitatively detected in the olfactory bulb, cerebrum, and medulla oblongata, than the pipette method. This appears to be because retention of the drug solution in the nasal cavity was substantially increased by active administration using a syringe pump in a direction opposite to the MC into the nasal cavity. In conclusion, the two methods of intranasal administration developed in this study can be expected to be extremely useful techniques for evaluating pharmacokinetics in rodents. The reverse cannulation method, in particular, could be useful for evaluating the full potential of nose-to-brain delivery of drug candidates.
(キーワード): Administration, Intranasal / Anesthesia, Inhalation / Animals / Biological Transport / 脳 (brain) / Drug Delivery Systems / Inulin / Mice / Nasal Mucosa
(出版サイトへのリンク): ● Publication site (DOI): 10.3791/58485
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 30507914; ● Summary page in Scopus @ Elsevier: 2-s2.0-85058115440

(DOI: 10.3791/58485, PubMed: 30507914, Elsevier: Scopus) Hisako Ibaraki, Takanori KANAZAWA, Yuuki Takashima, Hiroaki Okada and Yasuo Seta :
Transdermal anti-nuclear kappaB siRNA therapy for atopic dermatitis using a combination of two kinds of functional oligopeptide.,
International Journal of Pharmaceutics, Vol.542, No.1-2, 213-220, 2018.

(要約): Nucleic acid-based targeting of nuclear factor kappaB (NF-κB) is gaining attention as a treatment option for skin diseases like atopic dermatitis (AD). Transdermal administration improves patient quality of life because of non-invasive; however, siRNA delivery into the skin can be challenging owing to the barrier of tight junctions in the granular layer. Therefore, we aimed to develop a delivery system of siRNA for topical skin application using functional peptides. We previously reported that combined treatment with a cytoplasm-responsive stearylated-arginine-rich peptide (STR-CHRHC) and a tight junction opening peptide (AT1002) showed high siRNA permeability in the skin of AD-induced and normal mice. Here, we used murine macrophage RAW264.7 cells to examine siRNA permeation and the therapeutic effect of anti-NF-κB (RelA) siRNA (siRelA) complexed with STR-CHRHC and AT1002 for AD-induced mice. We showed that significantly higher siRNA cellular uptake occurs after this treatment as well as decreased TNF-α and IL-6 expression. Additionally, we showed that effective siRNA transdermal delivery occurs with the suppression of the tight junction protein ZO-1. Moreover, topical skin application of siRelA with STR-CHRHC and AT1002 improved AD-like symptoms in model mice. Thus, the combined treatment of STR-CHRHC and AT1002 could serve as an effective transdermal siRNA therapeutic system for AD.
(キーワード): Administration, Cutaneous / Animals / Dermatitis, Atopic / Interleukin-6 / 男性 (male) / Mice / Mice, Inbred C57BL / NF-kappa B / Oligopeptides / RAW 264.7 Cells / RNA, Small Interfering / Tumor Necrosis Factor-alpha / Zonula Occludens-1 Protein
(出版サイトへのリンク): ● Publication site (DOI): 10.1016/j.ijpharm.2018.03.026
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 29551748; ● Summary page in Scopus @ Elsevier: 2-s2.0-85044109906

(DOI: 10.1016/j.ijpharm.2018.03.026, PubMed: 29551748, Elsevier: Scopus) Takanori KANAZAWA, Mami Kaneko, Takaki Niide, Fuminari Akiyama, Shino Kakizaki, Hisako Ibaraki, Shunsuke Shiraishi, Yuuki Takashima, Toyofumi Suzuki and Yasuo Seta :
Enhancement of nose-to-brain delivery of hydrophilic macromolecules with stearate- or polyethylene glycol-modified arginine-rich peptide.,
International Journal of Pharmaceutics, Vol.530, No.1-2, 195-200, 2017.

(要約): Recently, nose-to-brain delivery is a highly versatile route, which, in combination with novel drugs being developed for treating intractable CNS diseases, is a promising approach for the treatment of disorders. Furthermore, nano-sized drug carriers may improve nose-to-brain drug delivery by their capability to increase the transmucosal penetration of the drugs across nasal mucosal tissue barrier. However, there is still not enough information regarding mechanism of absorption pathway from nasal cavity to brain using nanocarriers. In this study, to investigate the nose-to-brain transport pathway using nanocarriers, the distribution in whole brain, nasal mucosa, and trigeminal nerve after intranasal administration of two kinds of nanocarriers which have hydrophobic or hydrophilic moiety. We used CHHRRRRHHC peptide (CH2R4H2C) as basic peptide carriers, and modified with stearic acid (STR) as a hydrophobic moiety (STR-CH2R4H2C) or polyethylene glycol (PEG)-based block copolymer (PEG-PCL) as hydrophilic moiety (PEG-PCL-CH2R4H2C). The nose-to-brain drug delivery can be improved by using STR-CH2R4H2C and PEG-PCL-CH2R4H2C as carriers. Specifically, hydrophobic STR-CH2R4H2C is more suitable for the transport of drugs targeting the forebrain, while PEG-PCL-modified CH2R4H2C is more suitable for transporting drugs targeting the hindbrain or whole brain tissue. In conclusion, the results of this study support the possibility that drug delivery pathways can be controlled depending on the properties of different carrier complexes.
(キーワード): Administration, Intranasal / Animals / Arginine / Brain / Drug Delivery Systems / Male / Peptides / Polyethylene Glycols / Rats, Sprague-Dawley / Stearates
(出版サイトへのリンク): ● Publication site (DOI): 10.1016/j.ijpharm.2017.07.077
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 28757255; ● Search Scopus @ Elsevier (PMID): 28757255; ● Search Scopus @ Elsevier (DOI): 10.1016/j.ijpharm.2017.07.077

(DOI: 10.1016/j.ijpharm.2017.07.077, PubMed: 28757255) Takanori KANAZAWA, Kuniko Tamano, Kana Sogabe, Takahiro Endo, Hisako Ibaraki, Yuuki Takashima and Yasuo Seta :
Intra-articular Retention and Anti-arthritic Effects in Collagen-Induced Arthritis Model Mice by Injectable Small Interfering RNA Containing Hydrogel.,
Biological & Pharmaceutical Bulletin, Vol.40, No.11, 1929-1933, 2017.

(要約): Small interfering RNAs (siRNAs) are expected to offer a means of treating rheumatoid arthritis (RA) because they allow the specific silencing of genes related to RA pathogenesis. In our previous study, we reported that the siRNA targeted against RelA (anti-RelA siRNA), an important nuclear factor-kappaB (NF-κB) subdomain, was an effective therapeutic in atopic dermatitis and RA model animals. In this study, to develop an intra-articular injectable gel formulation against RA, we prepared a hydrogel that contains anti-RelA siRNA, and determined the in vitro release profile (%) and in vivo intra-articular retention of fluorescence-labeled model siRNA, and the anti-arthritic effects of the anti-RelA siRelA containing hydrogel in RA model mice. We selected the silk protein, sericin (SC), as an aqueous gel base, as it is a biocompatible and useful for forming hydrogels without a cross-linker. We showed that fluorescence-labeled model siRNA was continuously released from SC hydrogel in vitro, and retained in the knee joint of rats after injection of siRNA hydrogel. In addition, the knee joint thickness, clinical severity and incidence (%) in collagen-induced arthritis (CIA) mice as RA model treated with anti-RelA siRNA containing hydrogel were more improved than untreated, anti-RelA siRNA solution and negative control siRNA containing hydrogel group. Therefore, the intra-articular injectable sericin hydrogel formulation containing of anti-RelA siRNA could be a great potential therapeutic in rheumatoid arthritis.
(キーワード): Animals / Arthritis, Experimental / Arthritis, Rheumatoid / Drug Liberation / Genetic Therapy / Humans / Hydrogels / Injections, Intra-Articular / Joints / 男性 (male) / Mice / Mice, Inbred DBA / RNA, Small Interfering / Rats / Rats, Sprague-Dawley / Sericins / Transcription Factor RelA / Treatment Outcome
(出版サイトへのリンク): ● Publication site (DOI): 10.1248/bpb.b17-00481
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 29093340; ● Summary page in Scopus @ Elsevier: 2-s2.0-85034054281

(DOI: 10.1248/bpb.b17-00481, PubMed: 29093340, Elsevier: Scopus) Takanori KANAZAWA, Takahiro Endo, Naoki Arima, Hisako Ibaraki, Yuuki Takashima and Yasuo Seta :
Systemic delivery of small interfering RNA targeting nuclear factor κB in mice with collagen-induced arthritis using arginine-histidine-cysteine based oligopeptide-modified polymer nanomicelles.,
International Journal of Pharmaceutics, Vol.515, No.1-2, 315-323, 2016.

(要約): This study aimed to build an innovative system to deliver a systemic small interfering RNA (siRNA) treatment for rheumatoid arthritis. We combined arginine-histidine-cysteine based oligopeptide-modified polymer micelles with siRNA targeting the nuclear factor κB subunit, RelA (siRelA). This is a key molecule in the control of inflammation. We tested the cellular uptake of siRNA and its effects on inflammatory cytokine levels in vitro using synoviocytes, and siRNA distribution and therapeutic effects in vivo in mice with collagen-induced arthritis (CIA). These studies showed that arginine-histidine based oligopeptide modified micelles produced effective cellular siRNA uptake and suppressed inflammatory cytokine levels in synoviocytes. In vivo, these micelles produced marked accumulation of siRNAs in arthritic paws in CIA mice, with much less accumulation in healthy mice. The siRelA-polymer micelle complexes also produced more effective suppression of RelA mRNA expression and inflammatory cytokine levels in the arthritic paws of CIA mice and reduced their clinical symptom scores and paw thickness.
(キーワード): Animals / Arginine / Arthritis, Experimental / Arthritis, Rheumatoid / コラーゲン (collagen) / Cysteine / 細胞質分裂 (cytokinesis) / Disease Models, Animal / Histidine / 炎症 (inflammation) / 男性 (male) / Mice / Mice, Inbred DBA / Micelles / NF-kappa B / ナノ粒子 (nanoparticles) / Oligopeptides / Polymers / RNA, Messenger / RNA, Small Interfering / Synovial Membrane / Synoviocytes / Transcription Factor RelA
(出版サイトへのリンク): ● Publication site (DOI): 10.1016/j.ijpharm.2016.10.033
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 27765724; ● Summary page in Scopus @ Elsevier: 2-s2.0-84992035050

(DOI: 10.1016/j.ijpharm.2016.10.033, PubMed: 27765724, Elsevier: Scopus) Hisako Ibaraki, Takanori KANAZAWA, Yuuki Takashima, Hiroaki Okada and Yasuo Seta :
Development of an Innovative Intradermal siRNA Delivery System Using a Combination of a Functional Stearylated Cytoplasm-Responsive Peptide and a Tight Junction-Opening Peptide.,
Molecules, Vol.21, No.10, 1279, 2016.

(要約): As a new category of therapeutics for skin diseases including atopic dermatitis (AD), nucleic acids are gaining importance in the clinical setting. Intradermal administration is noninvasive and improves patients' quality of life. However, intradermal small interfering RNA (siRNA) delivery is difficult because of two barriers encountered in the skin: intercellular lipids in the stratum corneum and tight junctions in the stratum granulosum. Tight junctions are the major barrier in AD; therefore, we focused on functional peptides to devise an intradermal siRNA delivery system for topical skin application. In this study, we examined intradermal siRNA permeability in the tape-stripped (20 times) back skin of mice or AD-like skin of auricles treated with 6-carboxyfluorescein-aminohexyl phosphoramidite (FAM)-labeled siRNA, the tight junction modulator AT1002, and the functional cytoplasm-responsive stearylated peptide STR-CH2R4H2C by using confocal laser microscopy. We found that strong fluorescence was observed deep and wide in the epidermis and dermis of back skin and AD-like ears after siRNA with STR-CH2R4H2C and AT1002 treatment. After 10 h from administration, brightness of FAM-siRNA was significantly higher for STR-CH2R4H2C + AT1002, compared to other groups. In addition, we confirmed the nontoxicity of STR-CH2R4H2C as a siRNA carrier using PAM212 cells. Thus, our results demonstrate the applicability of the combination of STR-CH2R4H2C and AT1002 for effective intradermal siRNA delivery.
(キーワード): Administration, Topical / 吸着 (adsorption) / Animals / Cytoplasm / Dermatitis, Atopic / Drug Delivery Systems / Gene Transfer Techniques / Keratinocytes / 男性 (male) / Mice / Peptides / Permeability / RNA, Small Interfering / 皮膚 (skin) / Tight Junctions
(出版サイトへのリンク): ● Publication site (DOI): 10.3390/molecules21101279
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 27669207; ● Search Scopus @ Elsevier (PMID): 27669207; ● Search Scopus @ Elsevier (DOI): 10.3390/molecules21101279

(DOI: 10.3390/molecules21101279, PubMed: 27669207) Takanori KANAZAWA, Yuki Shizawa, Mayu Takeuchi, Kuniko Tamano, Hisako Ibaraki, Yasuo Seta, Yuki Takashima and Hiroaki Okada :
Topical Anti-Nuclear Factor-Kappa B Small Interfering RNA with Functional Peptides Containing Sericin-Based Hydrogel for Atopic Dermatitis.,
Pharmaceutics, Vol.7, No.3, 294-304, 2015.

(要約): The small interfering RNA (siRNA) is suggested to offer a novel means of treating atopic dermatitis (AD) because it allows the specific silencing of genes related to AD pathogenesis. In our previous study, we found that siRNA targeted against RelA, an important nuclear factor-kappa B (NF-κB) subdomain, with functional peptides, showed therapeutic effects in a mouse model of AD. In the present study, to develop a topical skin application against AD, we prepared a hydrogel containing anti-RelA siRNA and functional peptides and determined the intradermal permeation and the anti-AD effects in an AD mouse model. We selected the silk protein, sericin (SC), which is a versatile biocompatible biomaterial to prepare hydrogel as an aqueous gel base. We found that the siRNA was more widely delivered to the site of application in AD-induced ear skin of mice after topical application via the hydrogel containing functional peptides than via the preparation without functional peptides. In addition, the ear thickness and clinical skin severity of the AD-induced mice treated with hydrogel containing anti-RelA siRNA with functional peptides improved more than that of mice treated with the preparation formulated with negative siRNA.
(出版サイトへのリンク): ● Publication site (DOI): 10.3390/pharmaceutics7030294
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 26371030; ● Summary page in Scopus @ Elsevier: 2-s2.0-84941209734

(DOI: 10.3390/pharmaceutics7030294, PubMed: 26371030, Elsevier: Scopus) Takanori KANAZAWA, Tomohiro Hamasaki, Takahiro Endo, Kuniko Tamano, Kana Sogabe, Yasuo Seta, Tadaaki Ohgi and Hiroaki Okada :
Functional peptide nanocarriers for delivery of novel anti-RelA RNA interference agents as a topical treatment of atopic dermatitis.,
International Journal of Pharmaceutics, Vol.489, No.1-2, 261-267, 2015.

(要約): Small interfering RNAs (siRNAs) are a potential treatment of atopic dermatitis (AD) because they can specifically silence the gene expression of AD-related factors. However, siRNA alone cannot exert a sufficiently strong therapeutic effect due to low delivery efficiency to the target tissues and cells; simply increasing the amount used is not possible due to the possibility of off-target effects. We previously reported a novel class of therapeutic RNA interference (RNAi) agents called nkRNA(®) and PnkRNA(®), which have been shown to be effective in several disease models, have greater resistance to nuclease degradation than canonical siRNAs, and do not induce any immunotoxicity. In the present study, we describe a non-invasive and effective transdermal RNAi therapeutic system for atopic dermatitis that uses the functional cell-penetrating stearoyl-oligopeptide OK-102 as a cytoplasm-responsive nanocarrier for nkRNA(®) and PnkRNA(®). The two RNAi agents were targeted against RelA, a subclass of NF-κB (nuclear factor kappa B), and, as part of OK-102 complexes, they strongly silenced RelA mRNA in macrophage cells and demonstrated a significant therapeutic effect in a mouse model of AD. It was shown that OK-102-complexed RNAi agents were an efficient therapeutic system for AD and caused no adverse reactions.
(キーワード): Administration, Topical / Animals / Cell Line / Cell-Penetrating Peptides / Dermatitis, Atopic / Dinitrofluorobenzene / Interleukin-6 / Mice / Oligopeptides / Peptides / RNA (RNA) / RNA Interference / Transcription Factor RelA / Tumor Necrosis Factor-alpha
(出版サイトへのリンク): ● Publication site (DOI): 10.1016/j.ijpharm.2015.05.003
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 25956048; ● Summary page in Scopus @ Elsevier: 2-s2.0-84929191629

(DOI: 10.1016/j.ijpharm.2015.05.003, PubMed: 25956048, Elsevier: Scopus) Takanori KANAZAWA, Mamiko Yamazaki, Tsunehiko Fukuda, Yuuki Takashima and Hiroaki Okada :
Versatile nuclear localization signal-based oligopeptide as a gene vector.,
Biological & Pharmaceutical Bulletin, Vol.38, No.4, 559-565, 2015.

(要約): To develop a versatile nuclear-targeted gene vector, nuclear localization signal (NLS) oligopeptides combining cysteine (C), histidine (H), and stearic acid (STR) were investigated in this study. The original SV40 sequence (SV40: Pro-Lys-Lys-Lys-Arg-Lys-Val) was selected as the NLS sequence, and physical characterizations of various NLS-based oligopeptides (CSV40C, STR-CSV40C, and STR-CH2SV40H2C), including mean diameter, zeta-potential, complex condensation, and decondensation, were evaluated. In addition, cellular and nuclear uptake of plasmid DNA (pDNA) and gene expression in COS7 and dendritic cells (JAWS II) were determined. As a result, C and STR enhanced formation of a smaller and more stable nano-complex with pDNA based on ionic interactions, the disulfide linkage and hydrophobic interactions. STR-CSV40C and STR-CH2SV40H2C had significantly higher cellular uptake ability and transfection efficiency than SV40 and CSV40C. In particular, STR-CH2SV40H2C had higher nuclear uptake and gene expression efficiency than STR-CSV40C. Furthermore, STR-CH2SV40H2C could deliver pDNA to the nuclei and had high gene expression efficiency in dendritic cells. Our results indicate that STR-CH2SV40H2C is a promising gene delivery system in non- or slow-dividing cells.
(キーワード): Animals / COS Cells / Chlorocebus aethiops / DNA (DNA) / 遺伝子発現 (gene expression) / Genetic Vectors / Green Fluorescent Proteins / Mice / Nuclear Localization Signals / Oligopeptides / Plasmids
(出版サイトへのリンク): ● Publication site (DOI): 10.1248/bpb.b14-00706
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 25832636; ● Summary page in Scopus @ Elsevier: 2-s2.0-84928943983

(DOI: 10.1248/bpb.b14-00706, PubMed: 25832636, Elsevier: Scopus) Tatu Lajunen, Koji Hisazumi, Takanori KANAZAWA, Hiroaki Okada, Yasuo Seta, Marijo Yliperttula, Arto Urtti and Yuuki Takashima :
Topical drug delivery to retinal pigment epithelium with microfluidizer produced small liposomes.,
European Journal of Pharmaceutical Sciences, Vol.62, 23-32, 2014.

(要約): Drug delivery from topically instilled eye drops to the posterior segment of the eye has long been one of the greatest challenges of ocular drug development. We developed methods of liposome preparation utilizing a microfluidizer to achieve adjustable nanoparticle size (even less than 80 nm) and high loading capacity of plasmid DNA. The microfluidizing process parameters were shown to affect the size of the liposomes. Higher operating pressures and passage for at least 10 times through the microfluidizer produced small liposomes with narrow size distribution. The liposomes were physically stable for several months at +4°C. In vivo distribution of the optimized liposome formulations in the rat eyes was investigated with confocal microscopy of the histological specimens. Transferrin was used as a targeting ligand directed to retinal pigment epithelium. Size dependent distribution of liposomes to different posterior segment tissues was seen. Liposomes with the diameter less than 80 nm permeated to the retinal pigment epithelium whereas liposomes with the diameter of 100 nm or more were distributed to the choroidal endothelium. Active targeting was shown to be necessary for liposome retention to the target tissue. In conclusion, these microfluidizer produced small liposomes in eye drops are an attractive option for drug delivery to the posterior segment tissues of the eye.
(キーワード): Administration, Topical / Animals / DNA (DNA) / Drug Compounding / リポソーム (liposomes) / 男性 (male) / ナノ粒子 (nanoparticles) / Ophthalmic Solutions / Particle Size / Plasmids / Rats, Sprague-Dawley / Retinal Pigment Epithelium / Transferrin
(出版サイトへのリンク): ● Publication site (DOI): 10.1016/j.ejps.2014.04.018
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 24810393; ● Summary page in Scopus @ Elsevier: 2-s2.0-84901986883

(DOI: 10.1016/j.ejps.2014.04.018, PubMed: 24810393, Elsevier: Scopus) Takanori KANAZAWA, Kazuki Morisaki, Shohei Suzuki and Yuuki Takashima :
Prolongation of life in rats with malignant glioma by intranasal siRNA/drug codelivery to the brain with cell-penetrating peptide-modified micelles.,
Molecular Pharmaceutics, Vol.11, No.5, 1471-1478, 2014.

(要約): New therapeutic strategies are required to develop candidate drugs and ensure efficient delivery of these drugs to the brain and the central nervous system (CNS). Small interfering RNA (siRNA)-based therapies have been investigated as potential novel approaches for the treatment of brain disorders. Previously, we showed that Tat, a cell-penetrating peptide derived from HIV-Tat, and the modified block copolymers (MPEG-PCL-Tat) can form stable complexes with siRNA or can be loaded with an anticancer drug and efficiently deliver the drugs to the brain tissue via intranasal delivery. In this study, to develop a novel, efficient, and safe therapeutic strategy for managing brain disorders, we used MPEG-PCL-Tat micelles with a nose-to-brain delivery system to investigate its therapeutic effects on a rat model of malignant glioma using siRNA with a Raf-1 (siRaf-1)/camptothecin (CPT) codelivery system. MPEG-PCL-Tat and CPT-loaded MPEG-PCL-Tat can form a stable complex with siRNA with a particle size from 60 to 200 nm and a positive charge at N/P ratios up to 5. Additionally, MPEG-PCL-Tat/siRaf-1 and CPT-loaded MPEG-PCL-Tat/siRaf-1 have fostered cell death in rat glioma cells after the high cellular uptake of siRaf-1/drug by the MPEG-PCL-Tat carrier. Furthermore, compared to the unloaded MPEG-PCL-Tat/siRaf-1 complex, a CPT-loaded MPEG-PCL-Tat/siRaf-1 complex achieved the high therapeutic effect because of the additive effects of CPT and siRaf-1. These results indicate that drug/siRNA codelivery using MPEG-PCL-Tat nanomicelles with nose-to-brain delivery is an excellent therapeutic approach for brain and CNS diseases.
(キーワード): Animals / Antineoplastic Agents, Phytogenic / 脳 (brain) / Camptothecin / Cell Line / Cell Line, Tumor / Cell Survival / Cell-Penetrating Peptides / Disease Models, Animal / Glioma / MAP Kinase Kinase Kinases / 男性 (male) / Micelles / Proto-Oncogene Proteins c-raf / RNA, Small Interfering / Rats / Rats, Sprague-Dawley
(出版サイトへのリンク): ● Publication site (DOI): 10.1021/mp400644e
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 24708261; ● Summary page in Scopus @ Elsevier: 2-s2.0-84899854672

(DOI: 10.1021/mp400644e, PubMed: 24708261, Elsevier: Scopus) Takanori KANAZAWA, Fuminari Akiyama, Shino Kakizaki, Yuuki Takashima and Yasuo Seta :
Delivery of siRNA to the brain using a combination of nose-to-brain delivery and cell-penetrating peptide-modified nano-micelles.,
Biomaterials, Vol.34, No.36, 9220-9226, 2013.

(要約): The potential for RNA-based agents to serve as effective therapeutics for central nerve systems (CNS) disorders has been successfully demonstrated in vitro. However, the blood-brain barrier limits the distribution of systemically administered therapeutics to the CNS, posing a major challenge for drug development aimed at combatting CNS disorders. Therefore, the development of effective strategies to enhance siRNA delivery to the brain is of great interest in clinical and pharmaceutical fields. To improve the efficiency of small interfering RNA (siRNA) delivery to the brain, we developed a nose-to-brain delivery system combined with cell-penetrating peptide (CPP) modified nano-micelles comprising polyethylene glycol-polycaprolactone (PEG-PCL) copolymers conjugated with the CPP, Tat (MPEG-PCL-Tat). In this study, we describe intranasal brain delivery of siRNA or dextran (Mw: 10,000 Da) as a model siRNA, by using MPEG-PCL-Tat. Intranasal delivery of dextran with MPEG-PCL-Tat improved brain delivery compared to intravenous delivery of dextran either with or without MPEG-PCL-Tat. We also studied the intranasal transfer of MPEG-PCL-Tat to the brain via the olfactory and trigeminal nerves, the putative pathways to the brain from the nasal cavity. We found that MPEG-PCL-Tat accelerated transport along the olfactory and trigeminal nerve pathway because of its high permeation across the nasal mucosa.
(キーワード): Animals / 脳 (brain) / Cell-Penetrating Peptides / Dextrans / Fluorescence / Gene Transfer Techniques / Male / Micelles / ナノ粒子 (nanoparticles) / Nasal Mucosa / Olfactory Bulb / Polyesters / Polyethylene Glycols / RNA, Small Interfering / Rats / Rats, Sprague-Dawley / Tissue Distribution / Trigeminal Nerve / tat Gene Products, Human Immunodeficiency Virus
(出版サイトへのリンク): ● Publication site (DOI): 10.1016/j.biomaterials.2013.08.036
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 23992922; ● Summary page in Scopus @ Elsevier: 2-s2.0-84883756054

(DOI: 10.1016/j.biomaterials.2013.08.036, PubMed: 23992922, Elsevier: Scopus) Ko Tanaka, Takanori KANAZAWA, Shogo Horiuchi, Taichi Ando, Ken Sugawara, Yuuki Takashima, Yasuo Seta and Hiroaki Okada :
Cytoplasm-responsive nanocarriers conjugated with a functional cell-penetrating peptide for systemic siRNA delivery.,
International Journal of Pharmaceutics, Vol.455, No.1-2, 40-47, 2013.

(要約): To develop a gene carrier for cancer therapy by systemic injection, we synthesized methoxypolyethylene glycol-polycaprolactone (MPEG-PCL) diblock copolymers conjugated with a cytoplasm-responsive cell-penetrating peptide (CPP), CH2R4H2C (C, Cys; H, His; R, Arg). The carrier/small interfering RNA (siRNA) complexes (N/P ratio of 20) had a particle size of approximately 50 nm and stabilized the siRNA against RNase. The cellular uptake ability of the carrier/FAM-siRNA complexes with fetal bovine serum was significantly higher than that of naked FAM-siRNA. In addition, the carrier/anti-vascular endothelial growth factor siRNA (siVEGF) complexes attained a significantly greater silencing effect than naked siVEGF with low cytotoxicity, resulting from higher uptake, early endosomal escape, and efficient release from the complexes in the cytoplasm. Furthermore, intravenous injection of MPEG-PCL-CH2R4H2C/siVEGF complexes had a significantly higher anti-tumor effect in S-180 tumor-bearing mice, which could be attributed to the rigid compaction of siRNA by ionic interactions and disulfide linkages in the CPP polymer micelles in the blood, as well as higher release following cleavage of the disulfide bonds in the reductive cytosol. Taken together, our data demonstrated that these cytoplasm-responsive polymer micelles conjugated with multi-functional CPP, could facilitate siVEGF delivery to tumor tissues after systemic injection and could exert an extremely strong anti-tumor effect.
(キーワード): Animals / Cell Line, Tumor / Cell-Penetrating Peptides / Cytoplasm / Drug Carriers / 男性 (male) / Mice / Mice, Inbred ICR / ナノ粒子 (nanoparticles) / Neoplasms / Polyesters / Polyethylene Glycols / RNA, Small Interfering / Tumor Burden / Vascular Endothelial Growth Factor A
(出版サイトへのリンク): ● Publication site (DOI): 10.1016/j.ijpharm.2013.07.069
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 23911914; ● Summary page in Scopus @ Elsevier: 2-s2.0-84884131045

(DOI: 10.1016/j.ijpharm.2013.07.069, PubMed: 23911914, Elsevier: Scopus) Takanori KANAZAWA, Toshiaki Tamura, Mamiko Yamazaki, Yuuki Takashima and Hiroaki Okada :
Needle-free intravaginal DNA vaccination using a stearoyl oligopeptide carrier promotes local gene expression and immune responses.,
International Journal of Pharmaceutics, Vol.447, No.1-2, 70-74, 2013.

(要約): The vaginal mucosa is the most common site of infection for viruses that are transmitted through heterosexual intercourse, including human immunodeficiency virus and papillomavirus. Thus, in order to prevent or respond to these infections, strong vaginal immunity is required as the first line of defense. We previously investigated the use of a needle-free injector as a mucosal vaccination tool in rabbits and demonstrated that this is a promising method for stimulating vaginal gene expression and immune responses. In order to improve gene expression, we have examined local vaginal gene transfection efficiency using a non-needle jet injector combined with an effective peptide carrier in rabbits. The carrier used was a stearoyl (STR) peptide with Cys (C), Arg (R) and His (H) residues that form disulfide cross linkages via Cys (STR-CH2R4H2C) which was developed in our previous study. As a result, vaginal gene expression using the needle-free injector combined with STR-CH2R4H2C carrier was significantly improved compared to that without STR-CH2R4H2C carrier. Moreover, intravaginal pDNA vaccination by the needle-free injector combined with STR-CH2R4H2C carrier and CpG-ODN promoted not only local vaginal IgA and IgG, but also serum IgG secretion, to a degree significantly higher than that of naked pDNA.
(キーワード): Administration, Intravaginal / Animals / DNA (DNA) / 女性 (female) / 遺伝子発現 (gene expression) / Immunoglobulin A / Immunoglobulin G / Luciferases / Oligodeoxyribonucleotides / Oligopeptides / Rabbits / Vaccination / Vaccines, DNA / Vagina
(出版サイトへのリンク): ● Publication site (DOI): 10.1016/j.ijpharm.2013.02.018
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 23454850; ● Summary page in Scopus @ Elsevier: 2-s2.0-84874940571

(DOI: 10.1016/j.ijpharm.2013.02.018, PubMed: 23454850, Elsevier: Scopus) Hiroyuki Taki, Takanori KANAZAWA, Fuminari Akiyama, Yuuki Takashima and Hiroaki Okada :
Intranasal delivery of camptothecin-loaded tat-modified nanomicells for treatment of intracranial brain tumors.,
Pharmaceuticals, Vol.5, No.10, 1092-1102, 2012.

(要約): The blood-brain barrier is a substantial obstacle for delivering anticancer agents to brain tumors, and new strategies for bypassing it are sorely needed for brain tumor therapy. Intranasal delivery provides a practical, noninvasive method for delivering therapeutic agents to the brain. Intranasal application of nano-sized micelles that have been modified with Tat peptide facilitates brain delivery of fluorescent model materials. In this study, we evaluated a nose-to-brain delivery system for brain tumor therapy. We nasally administered the anti-tumor drug camptothecin (CPT) in solution and in methoxy poly(ethylene glycol) (MPEG)/poly(e-caprolactone) (PCL) amphiphilic block copolymers (MPEG-PCL) and cell penetrating peptide, Tat analog-modified MPEG-PCL (MPEG-PCL-Tat) MPEG-PCL-Tat to rats bearing intracranial glioma tumors and quantified the cytotoxicity against glioma cells, and the therapeutic effects. CPT-loaded MPEG-PCL-Tat micelles showed higher cytotoxicity than CPT-loaded MPEG-PCL. CPT-free MPEG-PCL-Tat didn't show any cytotoxicity, even at high concentrations (2 mmol/mL). CPT-loaded MPEG-PCL-Tat micelles significantly prolonged the median survival of rats. These results indicate that intranasal delivery of anti-cancer drugs with cell penetrating peptide-modified nanomicelles might be an effective therapy for brain tumors.
(出版サイトへのリンク): ● Publication site (DOI): 10.3390/ph5101092
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 24281259; ● Search Scopus @ Elsevier (PMID): 24281259; ● Search Scopus @ Elsevier (DOI): 10.3390/ph5101092

(DOI: 10.3390/ph5101092, PubMed: 24281259) Yukiko Nishino, Aya Kubota, Takanori KANAZAWA, Yuuki Takashima, Tetsuya Ozeki and Hiroaki Okada :
Improved intestinal absorption of a poorly water-soluble oral drug using mannitol microparticles containing a nanosolid drug dispersion.,
Journal of Pharmaceutical Sciences, Vol.101, No.11, 4191-4200, 2012.

(要約): A nozzle for a spray dryer that can prepare microparticles of water-soluble carriers containing various nanoparticles in a single step was previously developed in our laboratory. To enhance the solubility and intestinal absorption of poorly water-soluble drugs, we used probucol (PBL) as a poorly water-soluble drug, mannitol (MAN) as a water-soluble carrier for the microparticles, and EUDRAGIT (EUD) as a polymer vehicle for the solid dispersion. PBL-EUD-acetone-methanol and aqueous MAN solutions were simultaneously supplied through different liquid passages of the spray nozzle and dried together. PBL-EUD solid dispersion was nanoprecipitated in the MAN solution using an antisolvent mechanism and rapidly dried by surrounding it with MAN. PBL in the dispersion vehicle was amorphous and had higher physical stability according to powder X-ray diffraction and differential scanning calorimetry analysis. The bioavailability of PBL in PBL-EUD S-100-MAN microparticles after oral administration in rats was markedly higher (14- and 6.2-fold, respectively) than that of the original PBL powder and PBL-MAN microparticles. These results demonstrate that the composite microparticles containing a nanosized solid dispersion of a poorly water-soluble drug prepared using the spray nozzle developed by us should be useful to increase the solubility and bioavailability of drugs after oral administration.
(キーワード): Administration, Oral / Animals / Intestinal Absorption / 男性 (male) / Mannitol / Microscopy, Electron, Scanning / Microspheres / Nanostructures / 薬物速度論 (pharmacokinetics) / Rats / Rats, Sprague-Dawley / 溶解度 (solubility) / Water
(出版サイトへのリンク): ● Publication site (DOI): 10.1002/jps.23278
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 22864998; ● Summary page in Scopus @ Elsevier: 2-s2.0-84866387096

(DOI: 10.1002/jps.23278, PubMed: 22864998, Elsevier: Scopus) Takanori KANAZAWA, Ken Sugawara, Ko Tanaka, Shogo Horiuchi, Yuuki Takashima and Hiroaki Okada :
Suppression of tumor growth by systemic delivery of anti-VEGF siRNA with cell-penetrating peptide-modified MPEG-PCL nanomicelles.,
European Journal of Pharmaceutics and Biopharmaceutics, Vol.81, No.3, 470-477, 2012.

(要約): Small interfering RNAs (siRNAs) have potential applications for many diseases, such as cancer, since siRNAs can specifically silence disease-associated genes. However, effective siRNA carriers need to be developed to overcome the low siRNA stability in vivo, to form stable complexes and to facilitate intracellular uptake. In this study, to develop a carrier for systemic siRNA delivery, we prepared methoxy poly(ethylene glycol) (MPEG)/polycaprolactone (PCL) diblock copolymers conjugated with a cell-penetrating peptide, Tat, via a disulfide linkage, and evaluated their ability as an siRNA carrier. The particle size of MPEG-PCL-SS-Tat/siRNA complexes was approximately 100-200 nm. The cellular uptake ability after transfection with FAM-siRNA with MPEG-PCL-SS-Tat was significantly higher than that with FAM-siRNA only. MPEG-PCL-SS-Tat did not induce substantial cytotoxicity. Intravenous injection of MPEG-PCL-SS-Tat/anti-vascular endothelial growth factor (VEGF) siRNA (siVEGF) complexes achieved a high anti-tumor effect in tumor-bearing mice. These results suggest that MPEG-PCL-SS-Tat is a potentially effective siRNA carrier for silencing genes in vitro and in vivo.
(キーワード): Animals / Cell-Penetrating Peptides / Gene Products, tat / Gene Silencing / Injections, Intravenous / 男性 (male) / Mice / Mice, Inbred ICR / Micelles / ナノ粒子 (nanoparticles) / Particle Size / Polyesters / Polyethylene Glycols / RNA, Small Interfering / Sarcoma 180 / Transfection / Vascular Endothelial Growth Factor A
(出版サイトへのリンク): ● Publication site (DOI): 10.1016/j.ejpb.2012.04.021
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 22579732; ● Search Scopus @ Elsevier (PMID): 22579732; ● Search Scopus @ Elsevier (DOI): 10.1016/j.ejpb.2012.04.021

(DOI: 10.1016/j.ejpb.2012.04.021, PubMed: 22579732) Ko Tanaka, Takanori KANAZAWA, Ken Sugawara, Shogo Horiuchi, Yuuki Takashima and Hiroaki Okada :
A cytoplasm-sensitive peptide vector cross-linked with dynein light chain association sequence (DLCAS) enhances gene expression.,
International Journal of Pharmaceutics, Vol.419, No.1-2, 231-234, 2011.

(要約): We previously engineered a novel, non-viral, multifunctional gene vector (STR-CH(2)R(4)H(2)C) containing stearoyl (STR) and a block peptide consisting of Cys (C), His (H), and Arg (R). STR-CH(2)R(4)H(2)C forms a nano-complex with pDNA and is stabilized by electronic interactions and disulfide cross linkages. In blood, pDNA, a cytosol-sensitive gene vector, is released from the complex into the cytosol. The current study aimed to make STR-CH(2)R(4)H(2)C capable of active nuclear localization. The dynein light chain association sequence (DLCAS) was disulfide cross-linked to STR-CH(2)R(4)H(2)C/pDNA through disulfide linkages, and the gene expression ability of this DLCAS cross-linked gene vector was evaluated. We examined the gene transfection efficiency of S-180 cells transfected with the STR-CH(2)R(4)H(2)C/DLCAS/pDNA complex. STR-CH(2)R(4)H(2)C/DLCAS/pDNA showed significantly higher and faster gene expression compared with STR-CH(2)R(4)H(2)C/pDNA. We also evaluated the cellular uptake ability of STR-CH(2)R(4)H(2)C/DLCAS/Cy5-labeled pDNA complex. STR-CH(2)R(4)H(2)C/DLCAS/pDNA showed significantly lower cellular uptake compared with STR-CH(2)R(4)H(2)C/pDNA. This result indicates that high gene expression of STR-CH(2)R(4)H(2)C/DLCAS/pDNA does not facilitate its cellular uptake. In addition, the gene expression of DLCAS/STR-CH(2)R(4)H(2)C/pDNA in S-180 cells pretreated with the tubulin polymerization inhibitor, nocodazole (NCZ), was significantly lower than that in the absence of NCZ. These results indicate that the high transfection efficiency of DLCAS/STR-CH(2)R(4)H(2)C/pDNA is dependent on intra-cellular transport utilizing the microtubule motor protein, dynein. Taken together, our results suggest that DLCAS-modified STR-CH(2)R(4)H(2)C may be a promising gene delivery system.
(キーワード): Animals / Biological Transport / Cell Line, Tumor / Cytoplasm / DNA, Complementary / Dyneins / Gene Expression Regulation / Gene Transfer Techniques / Genetic Vectors / Mice / Nocodazole / Plasmids / Transfection / Tubulin Modulators
(出版サイトへのリンク): ● Publication site (DOI): 10.1016/j.ijpharm.2011.07.007
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 21782009; ● Summary page in Scopus @ Elsevier: 2-s2.0-80053575362

(DOI: 10.1016/j.ijpharm.2011.07.007, PubMed: 21782009, Elsevier: Scopus) Ayumu Nishida, Tsuyoshi Naganuma, Takanori KANAZAWA, Yuuki Takashima, Masaki Yamada and Hiroaki Okada :
The characterization of protein release from sericin film in the presence of an enzyme: towards fibroblast growth factor-2 delivery.,
International Journal of Pharmaceutics, Vol.414, No.1-2, 193-202, 2011.

(要約): Aqueous preparations of silk protein (sericin) films were prepared to evaluate their biodegradation properties. In the absence of trypsin, sericin film swelled rapidly, kept its shape, and remained unaltered for 28 days or longer due to form β-sheet structures. In the presence of trypsin, sericin film gradually degraded; since the rate depended on the concentration of trypsin, the films likely underwent enzymatic hydrolysis. Sericin film incorporating the model protein drug fluorescein isothiocyanate-albumin (FA) also gradually degraded in the presence of trypsin and resulted in the sustained release of FA for 2 weeks or longer; in contrast, FA release was quite slow in the absence of trypsin. It is expected that sericin film has potential as a biodegradable and drug-releasing carrier. To evaluate the practical applicability of sericin film for the repair of defective tissues, fibroblast growth factor-2 (FGF-2) was incorporated into sericin films and the films were implanted on skull defects in rats. Whereas FGF-2 release was suppressed in the absence of trypsin in vitro, it appears that FGF-2, immobilized by ionic interactions between sericin and FGF-2, can be sustained-released in vivo from films incorporating 2500 or 250 ng of FGF-2 to support the growth of tissue around wounds.
(キーワード): Animals / Biological Factors / Biological Products / Bombyx / Drug Carriers / Drug Compounding / Drug Delivery Systems / Fibroblast Growth Factor 2 / Fluorescein-5-isothiocyanate / Male / Rats / Rats, Sprague-Dawley / Sericins / Skull Fractures / Trypsin / Wound Healing
(出版サイトへのリンク): ● Publication site (DOI): 10.1016/j.ijpharm.2011.05.033
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 21619916; ● Summary page in Scopus @ Elsevier: 2-s2.0-79959717736

(DOI: 10.1016/j.ijpharm.2011.05.033, PubMed: 21619916, Elsevier: Scopus) Tamae Uchida, Takanori KANAZAWA, Misako Kawai, Yuuki Takashima and Hiroaki Okada :
Therapeutic effects on atopic dermatitis by anti-RelA short interfering RNA combined with functional peptides Tat and AT1002.,
The Journal of Pharmacology and Experimental Therapeutics, Vol.338, No.2, 443-450, 2011.

(要約): Atopic dermatitis (AD) has high morbidity and poor prognosis because safe and effective treatments are scarce. Recently, short interfering RNA (siRNA) has shown promise as an effective treatment for targeting specific aberrantly expressed genes. However, naked siRNAs are too inefficient because of various enzymatic, membrane, and cellular barriers. We previously reported that a Tat analog acting as a cell-penetrating peptide, combined with AT1002, which reversibly increases paracellular transport of molecules across the epidermal barrier in epidermis-disrupted mice and enhances the skin permeation of water-soluble siRNA. In the present study, to develop a novel treatment for AD, we determined the intradermal permeation of siRNAs and the antiallergic effects of a siRNA that silences RelA, a member of the nuclear factor-κB family, using Tat and AT1002 peptides in an AD mouse model. We first showed that the Tat analog and AT1002 delivered siRNA into the skin of ICR mice and, upon topical application to the AD-induced ears of NC/Nga mice, changed zonula occludens protein 1 expression. In addition, the silencing effects on the mRNA of RelA in JAWS II cells transfected with siRNA oligonucleotides for mouse RelA, complexed with Tat, were as effective as a commercial vector. Furthermore, the ear thickness, clinical skin severity, topical cytokine levels, and serum IgE production in AD model mice treated with anti-RelA siRNA with Tat and AT1002 were improved.
(キーワード): Animals / Cells, Cultured / Dermatitis, Atopic / Drug Delivery Systems / Drug Therapy, Combination / 女性 (female) / Gene Products, tat / Gene Silencing / 男性 (male) / Mice / Mice, Inbred ICR / Oligopeptides / RNA, Small Interfering / Skin Absorption / Transcription Factor RelA
(出版サイトへのリンク): ● Publication site (DOI): 10.1124/jpet.111.180042
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 21531792; ● Search Scopus @ Elsevier (PMID): 21531792; ● Search Scopus @ Elsevier (DOI): 10.1124/jpet.111.180042

(DOI: 10.1124/jpet.111.180042, PubMed: 21531792) Takanori KANAZAWA, Hiroyuki Taki, Ko Tanaka, Yuuki Takashima and Hiroaki Okada :
Cell-penetrating peptide-modified block copolymer micelles promote direct brain delivery via intranasal administration.,
Pharmaceutical Research, Vol.28, No.9, 2130-2139, 2011.

(要約): In order to develop non-invasive and effective nose-to-brain delivery of drugs, we synthesized Tat analog-modified methoxy poly(ethylene glycol) (MPEG)/poly(ϵ-caprolactone) (PCL) amphiphilic block copolymers through the ester bond. We evaluated the brain distribution of coumarin, acting as a model chemical, after intravenous or intranasal administration of MPEG-PCL. In addition, cellular uptake of coumarin by rat glioma cells transfected with coumarin-loaded MPEG-PCL or MPEG-PCL-Tat was determined. Finally, we determined the brain distribution and biodistribution after intranasal administration of coumarin-loaded MPEG-PCL-Tat. The amount of coumarin in the brain after intranasal administration was significantly higher than that after intravenous administration. In addition, cellular uptake of coumarin using MPEG-PCL was the lowest, while cellular uptake of coumarin using Tat-modified MPEG-PCL (MPEG-PCL-Tat) was higher than that of MPEG-PCL. Therefore, the brain distribution of coumarin administered using MPEG-PCL-Tat was significantly greater than that using MPEG-PCL. Then, the coumarin distribution after MPEG-PCL-Tat administration in non-targeted tissues (lung, liver, heart, kidney and spleen) was lower than that after coumarin administration without nanomicelles. We have demonstrated that utilization of nano-sized micelles modified with Tat can facilitate direct intranasal brain delivery.
(キーワード): Administration, Intranasal / Animals / 脳 (brain) / Brain Neoplasms / Cell Line, Tumor / Cell-Penetrating Peptides / Coumarins / Drug Carriers / Glioma / Injections, Intravenous / Micelles / Neoplasm Transplantation / Particle Size / Peptide Fragments / Polyesters / Polyethylene Glycols / Rats / Rats, Sprague-Dawley / Tissue Distribution / tat Gene Products, Human Immunodeficiency Virus
(出版サイトへのリンク): ● Publication site (DOI): 10.1007/s11095-011-0440-7
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 21499835; ● Summary page in Scopus @ Elsevier: 2-s2.0-80054735802

(DOI: 10.1007/s11095-011-0440-7, PubMed: 21499835, Elsevier: Scopus) Tamae Uchida, Takanori KANAZAWA, Yuuki Takashima and Hiroaki Okada :
Development of an efficient transdermal delivery system of small interfering RNA using functional peptides, Tat and AT-1002.,
Chemical & Pharmaceutical Bulletin, Vol.59, No.2, 196-201, 2011.

(要約): Topical use of small interfering RNA (siRNA) as a therapeutic nucleic acid is increasingly studied for the treatment of skin diseases and for the improvement of skin properties. However, naked siRNA transdermal delivery is limited by its low stability in the body and low permeability into target cells. This is due to various skin barriers such as the stratum corneum that has multiple lipid bilayers and epidermal layers that have tight junctions. In this study, we investigate non-invasive transdermal siRNA delivery using two functional peptides: AT1002, which is a tight junction modulator and 6-mer synthetic peptide belonging to a novel class of compounds that reversibly increases paracellular transport of molecules across the epithelial barrier; and Tat, which is a cell-penetrating peptide applicable as a transdermal siRNA delivery enhancer. We examined whether expression of the tight junction protein zonula occludens protein 1 (ZO-1) was detected in mouse skin applied with AT1002. Additionally, siRNA stabilities for RNaseA using Tat and AT1002 were assessed. We also determined the intradermal delivery efficiency of siRNA using functional peptides by confocal laser microscopy of fluorescently labeled siRNA in mouse skin. We found that the Tat analog and AT1002 strongly increased siRNA stability against RNaseA. In addition, ZO-1 disappeared from the skin after treatment with AT1002, yet recovered with time after washing. Finally, we also found that Tat and AT1002 peptides accelerate transdermal siRNA delivery both widely and effectively. Thus, combination of Tat and AT1002 is expected to be a transdermal delivery enhancer of siRNA.
(キーワード): Administration, Cutaneous / Animals / Cell Line / Drug Delivery Systems / 女性 (female) / Keratinocytes / 男性 (male) / Mice / Mice, Inbred ICR / Oligopeptides / Peptide Fragments / RNA, Small Interfering / tat Gene Products, Human Immunodeficiency Virus
(出版サイトへのリンク): ● Publication site (DOI): 10.1248/cpb.59.196
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 21297299; ● Summary page in Scopus @ Elsevier: 2-s2.0-79551494663

(DOI: 10.1248/cpb.59.196, PubMed: 21297299, Elsevier: Scopus) Ayumu Nishida, Masaki Yamada, Takanori KANAZAWA, Yuuki Takashima, Kiyohisa Ouchi and Hiroaki Okada :
Sustained-release of protein from biodegradable sericin film, gel and sponge.,
International Journal of Pharmaceutics, Vol.407, No.1-2, 44-52, 2011.

(要約): A silk protein, sericin, contains 18 kinds of amino acids, mostly polar side chains forming a complex of three principal polypeptides. The major polypeptides exhibit hydrophobic characteristics by forming a β-sheet structure in a hydrate state. As a drug-releasing biomaterial made by an aqueous process without using any cross linker, sericin is expected to form various hydrophobic dosage forms. However, its dosage form, with respect to the molecular weight and concentration of sericin, and its biodegradation behavior has not been studied in detail. In this study, the film, gel and sponge of sericin were prepared and examined to determine the release properties of the charged protein, fluorescein isothiocyanate-albumin (FA). The film and gel, as solid and semisolid forms, respectively, were also evaluated for their biodegradation behavior. For in vitro release, FA was sustained-released from these preparations. The concentration and dosage form markedly affected FA release. For in vivo biodegradation, the sericin preparations implanted subcutaneously in rats gradually decreased in size and weight. Histological examination indicated no marked inflammation at the site. As for in vivo release, FA remained for 3-6 weeks or more in rats. These findings suggest that sericin is suitable for use as a drug-releasing biomaterial.
(キーワード): Animals / Delayed-Action Preparations / Drug Implants / Excipients / Fluorescein-5-isothiocyanate / Gels / Hydrophobic and Hydrophilic Interactions / 男性 (male) / 分子量 (molecular weight) / Rats / Rats, Sprague-Dawley / Sericins / Serum Albumin / Time Factors
(出版サイトへのリンク): ● Publication site (DOI): 10.1016/j.ijpharm.2011.01.006
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 21238562; ● Summary page in Scopus @ Elsevier: 2-s2.0-79952315804

(DOI: 10.1016/j.ijpharm.2011.01.006, PubMed: 21238562, Elsevier: Scopus) Ko Tanaka, Takanori KANAZAWA, Takaya Ogawa, Yumiko Suda, Yuuki Takashima, Tsunehiko Fukuda and Hiroaki Okada :
A novel, bio-reducible gene vector containing arginine and histidine enhances gene transfection and expression of plasmid DNA.,
Chemical & Pharmaceutical Bulletin, Vol.59, No.2, 202-207, 2011.

(要約): We have engineered a novel, non-viral, multifunctional gene vector (STR-CH(2)R(4)H(2)C) that contained stearoyl (STR) and a block peptide consisting of Cys (C), His (H), and Arg (R). STR-CH(2)R(4)H(2)C can form a stable nano-complex with plasmid DNA (pDNA) based on electronic interactions and disulfide cross linkages. In this study, we evaluated the efficacy of STR-CH(2)R(4)H(2)C as a gene vector. We first determined the optimal weight ratio for STR-CH(2)R(4)H(2)C/pDNA complexes. The complexes with a weight ratio of 50 showed the highest transfection efficacy. We also examined the transfection efficacy of STR-CH(2)R(4)H(2)C/pDNA complexes with or without serum and compared STR-CH(2)R(4)H(2)C/pDNA transfection efficacy with that of Lipofectamine. Even in the presence of serum, STR-CH(2)R(4)H(2)C showed higher transfection efficacy than did Lipofectamine. In addition, we determined the mechanism of transfection of the STR-CH(2)R(4)H(2)C/pDNA complexes using various cellular uptake inhibitors and evaluated its endosomal escape ability using chloroquine. Macropinocytosis was main cellular uptake pathway of STR-CH(2)R(4)H(2)C/pDNA complexes. Our results suggested that STR-CH(2)R(4)H(2)C is a promising gene delivery system.
(キーワード): Animals / Arginine / COS Cells / Chlorocebus aethiops / DNA, Complementary / Genetic Vectors / Histidine / Plasmids / Transfection / Up-Regulation
(出版サイトへのリンク): ● Publication site (DOI): 10.1248/cpb.59.202
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 21297300; ● Summary page in Scopus @ Elsevier: 2-s2.0-79551488608

(DOI: 10.1248/cpb.59.202, PubMed: 21297300, Elsevier: Scopus) Ayumu Nishida, Masaki Yamada, Takanori KANAZAWA, Yuuki Takashima, Kiyohisa Ouchi and Hiroaki Okada :
Use of silk protein, sericin, as a sustained-release material in the form of a gel, sponge and film.,
Chemical & Pharmaceutical Bulletin, Vol.58, No.11, 1480-1486, 2010.

(要約): To evaluate the usability of silk protein (sericin, SC) as a sustained-release material, the physicochemical properties of SC and the release profiles of model drugs from SC gel, sponge and film were studied. Heat aids the dissolution of SC. The molecular weight of SC tended to decrease as the heating temperature and heating time increased. The gel and sponge formed by SC were moldable and consisted of high molecular weight SC polymers (250 kDa and about 400 kDa). SC film was easily broken and exhibited elastic distortion. The addition of moisture-retaining plasticizer (glycerin and sorbitol) improved the film-forming characteristics of SC. The results suggested that SC is practical as a moldable gel and sponge, and as a tensible film. To evaluate the release profiles of small molecules, fluorescein isothiocyanate-dextran ((1) FD4, 4 kDa and (2) FD70, 70 kDa) were used as two model drugs with significantly different molecular weights, and fluorescein isothiocyanate-albumin ((3) FA, 66 kDa) was used as a charged drug. Each was formulated in SC gel, sponge and film. In each preparation, the release rate of the model drugs tended to be FA<FD70<FD4. FA, which has a large molecular weight and negative charge, was released for the longest period of time (≥1 week) from each preparation. The results suggest that SC is usable as an aqueous sustained-release material for high molecular weight drugs. Furthermore, if the drug is charged, its release can be sustained for an extended time.
(キーワード): Animals / Bombyx / Delayed-Action Preparations / Gels / Pharmaceutical Preparations / Sericins
(出版サイトへのリンク): ● Publication site (DOI): 10.1248/cpb.58.1480
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 21048340; ● Summary page in Scopus @ Elsevier: 2-s2.0-78049452879

(DOI: 10.1248/cpb.58.1480, PubMed: 21048340, Elsevier: Scopus) Ko Tanaka, Takanori KANAZAWA, Takaya Ogawa, Yuuki Takashima, Tsunehiko Fukuda and Hiroaki Okada :
Disulfide crosslinked stearoyl carrier peptides containing arginine and histidine enhance siRNA uptake and gene silencing,
International Journal of Pharmaceutics, Vol.398, No.1-2, 219-224, 2010.

(要約): The siRNA has been expected to apply for several diseases such as cancer since siRNA specifically silences the disease-associated genes. However, effective gene carriers should be developed to overcome the low siRNA stability in vivo, form stable complexes and facilitate intracellular uptake of siRNA. In this study, to develop a safe and efficient siRNA carrier, stearoyl (STR) peptides with Cys (C), Arg (R), and His (H) residues that can form disulfide cross linkages via Cys (C) were synthesized, and their suitability as siRNA carriers was evaluated. The particle size of STR-CH(2)R(4)H(2)C/siRNA complexes was about 100 nm. The cellular uptake ability after transfection with FAM-siRNA with STR-CH(2)R(4)H(2)C, CH(2)R(4)H(2)C, or STR-GH(2)R(4)H(2)G was significantly higher than that with FAM-siRNA only. STR-CH(2)R(4)H(2)C showed the highest cellular uptake ability when compared with CH(2)R(4)H(2)C and STR-GH(2)R(4)H(2)G. STR-CH(2)R(4)H(2)C did not induce substantial cytotoxicity. The intratumor injection of STR-CH(2)R(4)H(2)C/vascular endothelial growth factor (VEGF) siRNA (siVEGF) complexes achieved a high anti-tumor effect in tumor bearing mice. These results suggest STR-CH(2)R(4)H(2)C has potential of effective siRNA carrier possible to exercise silencing effect in vitro and in vivo.
(キーワード): Animals / Arginine / Cross-Linking Reagents / Disulfides / Drug Carriers / Gene Silencing / Histidine / Humans / 男性 (male) / Mice / Mice, Inbred ICR / Peptides / Protein Transport / RNA, Small Interfering / Tumor Cells, Cultured / Xenograft Model Antitumor Assays
(出版サイトへのリンク): ● Publication site (DOI): 10.1016/j.ijpharm.2010.07.038
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 20674725; ● Summary page in Scopus @ Elsevier: 2-s2.0-77956220454

(DOI: 10.1016/j.ijpharm.2010.07.038, PubMed: 20674725, Elsevier: Scopus) Ko Tanaka, Takanori KANAZAWA, Yasunori Shibata, Yumiko Suda, Tsunehiko Fukuda, Yuuki Takashima and Hiroaki Okada :
Development of cell-penetrating peptide-modified MPEG-PCL diblock copolymeric nanoparticles for systemic gene delivery.,
International Journal of Pharmaceutics, Vol.396, No.1-2, 229-238, 2010.

(要約): To develop a safe and efficient systemic non-viral gene vector, methoxy poly(ethylene glycol) (MPEG)/poly(epsilon-caprolactone) (PCL) diblock copolymers conjugated with a Tat analog through the ester or disulfide linkage were synthesized and their suitability as a systemic non-viral gene carrier evaluated. The physicochemical properties of the MPEG-PCL diblock copolymers were determined by GPC, (1)H NMR and FT-IR spectroscopy. The particle sizes and in vitro (COS7 and S-180 cells) transfection efficiencies and cytotoxicity were evaluated. Furthermore, the luciferase activity was then determined in various tissues after intravenous injection of MPEG-PCL-SS-Tat/pCMV-Luc complex into mice bearing S-180 cells. The particle sizes of the MPEG-PCL-Tat copolymers with or without pDNA were about 40 and 60nm, respectively. The luciferase activity in COS7 cells transfected with pCMV-Luc with MPEG-PCL-ester-Tat or MPEG-PCL-SS-Tat was higher than that with pDNA only. MPEG-PCL-SS-Tat greatly increased the transfection efficiency compared to MPEG-PCL-ester-Tat in COS7 and S-180 cells. In an in vitro cytotoxicity test MPEG-PCL-SS-Tat did not induce any remarkable cytotoxicity. In an in vivo experiment, the synthesized MPEG-PCL-SS-Tat copolymers promoted the delivery and expression of pDNA into tumor tissue in tumor-bearing mice. In conclusion, this vector might be applicable as a tumor-targeting non-viral systemic gene carrier in the clinical setting.
(キーワード): Animals / COS Cells / Cell Membrane Permeability / Cell Survival / Chlorocebus aethiops / Chromatography, Gel / 女性 (female) / Gene Expression Regulation, Neoplastic / Genes, Reporter / Injections, Intravenous / Magnetic Resonance Spectroscopy / Mice / Mice, Inbred ICR / ナノ粒子 (nanoparticles) / Particle Size / Peptide Fragments / Polyesters / Polyethylene Glycols / Sarcoma 180 / Spectroscopy, Fourier Transform Infrared / Transfection / tat Gene Products, Human Immunodeficiency Virus
(出版サイトへのリンク): ● Publication site (DOI): 10.1016/j.ijpharm.2010.06.028
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 20600726; ● Summary page in Scopus @ Elsevier: 2-s2.0-77955054853

(DOI: 10.1016/j.ijpharm.2010.06.028, PubMed: 20600726, Elsevier: Scopus) Takanori KANAZAWA, Yuuki Takashima, Toshiaki Tamura, Miki Tsuchiya, Yasunori Shibata, Haruhide Udagawa and Hiroaki Okada :
Local gene expression and immune responses of vaginal DNA vaccination using a needle-free injector.,
International Journal of Pharmaceutics, Vol.396, No.1-2, 11-16, 2010.

(要約): The vaginal mucosa is the most common site of initiation of virus infections that are transmitted through heterosexual intercourse, including HIV and papillomavirus. Thus, in order to prevent or treat these infections, strong vaginal immunity is required as the first line of defense. In this study, to establish a less invasive, safe, convenient and effective immunization method, we examined the local (skin and vagina) gene transfection efficiency of a non-needle jet injector for daily insulin injection. In the skin experiment, the needle-free injector resulted in a marked increase in marker gene expression, compared to the conventional needle-syringe injection. In addition, intradermal DNA vaccination using the needle-free injector dramatically induced IFN-gamma and antibody systemic responses in mice. Furthermore, we investigated the applicability of the needle-free injector as a vaginal vaccination tool in rabbits. Vaginal gene expression using the needle-free injector was significantly greater than that using needle-syringe injection. Moreover, intravaginal vaccination by the needle-free injector promoted vaginal IgA secretion and IFN-gamma mRNA expression in the blood lymphocytes, to a degree significantly higher than that by needle-syringe injection. In conclusion, local vaginal DNA vaccination using a needle-free jet injector is a promising approach for the prevention and treatment of mucosal infectious diseases.
(キーワード): Administration, Intravaginal / Animals / Cells, Cultured / 女性 (female) / Gene Expression Regulation / Gene Transfer Techniques / Immunity, Cellular / Immunity, Humoral / Immunity, Mucosal / Immunoglobulin G / Injections, Jet / Interferon-gamma / 男性 (male) / Mice / Mice, Inbred C57BL / Mucous Membrane / Rabbits / Rats / Rats, Wistar / Sexually Transmitted Diseases, Viral / 皮膚 (skin) / Vaccines, DNA / Vagina
(出版サイトへのリンク): ● Publication site (DOI): 10.1016/j.ijpharm.2010.05.040
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 20621704; ● Summary page in Scopus @ Elsevier: 2-s2.0-77955049175

(DOI: 10.1016/j.ijpharm.2010.05.040, PubMed: 20621704, Elsevier: Scopus) Takanori KANAZAWA, Yuuki Takashima, Yasunori Shibata, Miki Tsuchiya, Toshiaki Tamura and Hiroaki Okada :
Effective vaginal DNA delivery with high transfection efficiency is a good system for induction of higher local vaginal immune responses.,
The Journal of Pharmacy and Pharmacology, Vol.61, No.11, 1457-1463, 2009.

(要約): To investigate the local vaginal and systemic immune responses of effective vaginal DNA delivery with high transfection efficiency, we determined the effects on Th1-dependent cytokine (interferon-gamma) production in spleen and inguinal lymph node cells and antibody responses of vaginal pDNA immunization with a cell-penetrating peptide, and compared our vaginal immunization with intradermal and intranasal immunizations. Mice were immunized by vaginal, nasal or dermal administration of pCMV-OVA with or without peptide carriers, and serum, vaginal fluids, spleen and inguinal cells were harvested. The serum immunoglobulin (Ig)G(2a) and vaginal IgA antibody responses were determined by sandwich enzyme-linked immunosorbent assay (ELISA). The interferon-gamma production from spleen cells or inguinal lymph node cells was determined by an ELISA kit. The direct vaginal immunization strongly induced IgA in the vaginal fluids and interferon-gamma production in the local lymph node draining from the vagina. In addition, co-vaccination with the peptide carriers elevated these immune responses compared with vaccination with pCMV-OVA alone. Vaginal immunization with high transfection efficiency promoted vaginal IgA production to a significantly greater extent than intradermal or nasal immunization. These results suggested that direct vaginal DNA vaccines under high transfection conditions induced higher local vaginal antibody than that by intranasal or intradermal administration, and peptide carriers effectively elevated mucosal immune responses. Therefore, this vaginal DNA vaccination method may be expected to be useful in the prevention and treatment methods for vaginal infectious diseases such as HIV infection.
(キーワード): Administration, Intravaginal / Animals / 女性 (female) / Immunity, Mucosal / Immunization / Immunoglobulin A / Immunoglobulin G / Interferons / Lymph Nodes / Mice / Mice, Inbred C57BL / Mice, Inbred ICR / Ovalbumin / Spleen / Th1 Cells / Transfection / Vaccines, DNA / Vagina
(出版サイトへのリンク): ● Publication site (DOI): 10.1211/jpp/61.11.0004
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 19903370; ● Search Scopus @ Elsevier (PMID): 19903370; ● Search Scopus @ Elsevier (DOI): 10.1211/jpp/61.11.0004

(DOI: 10.1211/jpp/61.11.0004, PubMed: 19903370) Takanori KANAZAWA, Yuuki Takashima, Motoko Murakoshi, Yuka Nakai and Hiroaki Okada :
Enhancement of gene transfection into human dendritic cells using cationic PLGA nanospheres with a synthesized nuclear localization signal.,
International Journal of Pharmaceutics, Vol.379, No.1, 187-195, 2009.

(要約): Effective delivery of DNA encoding antigen into the dendritic cells (DCs), which are non-dividing cells, is very important for the development of DNA vaccines. In a previous study, we developed the PLGA nanospheres that contained a cationic nanomaterial and showed high transfection efficiency in COS7 cells, which divide. In the present study, to produce an effective vector for the DNA vaccines, the gene expression and intracellular trafficking of pDNA complexed with PLGA/PEI nanospheres, in combination with an NF-kappaB analog as a nuclear localization signal (NLS) and electroporation were evaluated in human monocyte-derived DCs (hMoDCs). Cellular uptake of pDNA both in COS7 cells and hMoDCs was enhanced using the PLGA/PEI nanospheres. On the other hand, the PLGA/PEI nanospheres significantly promoted the transfection in COS7 cells, but had almost no effect on transfection in hMoDCs. The intranuclear transport of pDNA by PLGA/PEI nanospheres in COS7 cells was significantly higher than that in hMoDCs. These results indicate that pDNA complexed with PLGA/PEI nanospheres cannot enter into the nuclei of non-dividing cells. However, PLGA/PEI nanospheres combinated with NLS and electroporation (experimental permeation enhancer) greatly elevated the transfection efficiency by improvement of not only intracellular uptake but also intranuclear transport of pDNA in the hMoDCs. Thus, this delivery system using nanospheres combined with synthesized NLS might be applicable to DC-based gene vaccines when much non-invasive application such as needle-free injector should be required.
(キーワード): Animals / COS Cells / Cations / Chlorocebus aethiops / Dendritic Cells / Electroporation / Gene Expression Regulation / Humans / Lactic Acid / Nanospheres / Nuclear Localization Signals / Polyethyleneimine / Polyglycolic Acid / Polylactic Acid-Polyglycolic Acid Copolymer / Transfection / Vaccines, DNA
(出版サイトへのリンク): ● Publication site (DOI): 10.1016/j.ijpharm.2009.06.015
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 19555751; ● Summary page in Scopus @ Elsevier: 2-s2.0-68649090915

(DOI: 10.1016/j.ijpharm.2009.06.015, PubMed: 19555751, Elsevier: Scopus) Aki Kimura, Yosuke Kamo, Yuuki Takashima, Takanori KANAZAWA, Hiroaki Okada and Tsunehiko Fukuda :
Synthesis and transport activities of HIV-Tat peptide-modified cholesterol pullulan,
Chemistry Letters, Vol.38, No.10, 970-971, 2009.

(出版サイトへのリンク): ● Publication site (DOI): 10.1246/cl.2009.970
(文献検索サイトへのリンク): ● Summary page in Scopus @ Elsevier: 2-s2.0-84865367541

(DOI: 10.1246/cl.2009.970, Elsevier: Scopus) Takanori KANAZAWA, Yuuki Takashima, Shunichi Hirayama and Hiroaki Okada :
Effects of menstrual cycle on gene transfection through mouse vagina for DNA vaccine.,
International Journal of Pharmaceutics, Vol.360, No.1-2, 164-170, 2008.

(要約): Human immunodeficiency virus (HIV) infections mainly occur through the vaginal and rectal mucosal membranes. In the present study, to develop a DNA vaginal vaccine against viral and bacterial infections, the effects of the menstrual cycle on DNA transfection through the vaginal mucosa in female mice and transfection enhancement by electroporation, a chelating agent, cell-penetrating peptides (CPP) and nuclear localizing signals (NLS) were investigated. The transfection efficiencies of a marker plasmid DNA (pDNA), pCMV-Luc, on the vaginal mucosal membrane in mice at the stages of metestrus and diestrus were significantly higher than those at the stages of proestrus and estrus. The gene expression was markedly enhanced by electroporation and by pretreatment with the chelating agent. The highest level of expression was obtained by 2h pretreatment with 5% citric acid solution combined with electroporation with 15 pulses at 250 V/cm for 5 milliseconds (ms). Furthermore, a synergistic promoting effect on pDNA transfection was obtained by co-administration of CPP, the Tat peptide analog, and NLS, the NF-kappaB analog. These results indicate that effective DNA vaccination administered through the vaginal tract is possible by selecting the menstrual stage and overcoming the mucosal barrier using a combination of methods that promotes uptake.
(キーワード): Animals / Citric Acid / Electroporation / Estrous Cycle / Excipients / 女性 (female) / 遺伝子発現 (gene expression) / Gene Products, tat / Genes, Reporter / Luciferases / Mice / Mice, Inbred ICR / NF-kappa B / Peptides / Plasmids / Transfection / Vaccines, DNA / Vagina
(出版サイトへのリンク): ● Publication site (DOI): 10.1016/j.ijpharm.2008.04.038
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 18573624; ● Summary page in Scopus @ Elsevier: 2-s2.0-47049118557

(DOI: 10.1016/j.ijpharm.2008.04.038, PubMed: 18573624, Elsevier: Scopus) Yuuki Takashima, Ryo Saito, Azusa Nakajima, Motoko Oda, Aki Kimura, Takanori KANAZAWA and Hiroaki Okada :
Spray-drying preparation of microparticles containing cationic PLGA nanospheres as gene carriers for avoiding aggregation of nanospheres.,
International Journal of Pharmaceutics, Vol.343, No.1-2, 262-269, 2007.

(要約): Preparation of nano-sized particles using lyophilization, which is a standard drying technique for high-molecular-weight compounds such as bioactive peptides, proteins, plasmid DNA and siRNA, often results in particle aggregation. In this study, spray-drying was applied for preparation of cationic PLGA nanospheres as gene delivery vectors in order to minimize aggregation and loss of gene transfection efficiency. PLGA nanoparticle emulsions were prepared by dropping an acetone/methanol mixture (2/1) containing PLGA and a cationic material, such as PEI, DOTMA, DC-Chol or CTAB, into distilled water with constant stirring. The PLGA nanosphere emulsion was dried with mannitol by spray-drying, and mannitol microparticles containing PLGA nanospheres were obtained. Mean particle diameter of spray dried PLGA particles was 100-250 nm, which was similar to that of the nano-emulsion before drying, whereas the lyophilized PLGA particles showed increased particle diameter due to particle aggregation. PEI, DOTMA and DC-Chol were useful for maintaining nanoparticle size and conferring positive charge to nanospheres. Transfection of pDNA (pCMV-Luc) using these spray-dried cationic PLGA nanospheres yielded high luciferase activity in COS-7 cells, particularly with PLGA/PEI nanospheres. The present spray-drying technique is able to provide cationic PLGA nanospheres, and may improve redispersal and handling properties.
(キーワード): Animals / COS Cells / Chlorocebus aethiops / DNA (DNA) / Drug Compounding / 女性 (female) / Freeze Drying / 遺伝子発現 (gene expression) / Green Fluorescent Proteins / Lactic Acid / Luciferases / Mannitol / Mice / Mice, Inbred BALB C / Nanospheres / Particle Size / Plasmids / Polyethyleneimine / Polyglycolic Acid / Polylactic Acid-Polyglycolic Acid Copolymer / Polymers / Tissue Distribution / Transfection
(出版サイトへのリンク): ● Publication site (DOI): 10.1016/j.ijpharm.2007.05.042
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 17628365; ● Summary page in Scopus @ Elsevier: 2-s2.0-34548248299

(DOI: 10.1016/j.ijpharm.2007.05.042, PubMed: 17628365, Elsevier: Scopus)

MISC

研究者総覧に該当データはありませんでした。

総説・解説

Hisako Ibaraki and Takanori KANAZAWA :
In Vivo Topical and Systemic Distribution Kinetics of Liposomes with Various Properties for Application to Drug Delivery Systems,
Sensors and Materials, Vol.34, No.3(1), 987-1005, Mar. 2022.

(出版サイトへのリンク): ● Publication site (DOI): 10.18494/SAM3673
(文献検索サイトへのリンク): ● Summary page in Scopus @ Elsevier: 2-s2.0-85125877151

(DOI: 10.18494/SAM3673, Elsevier: Scopus) 茨木ひさ子, 金沢貴憲 :
細胞間隙を標的としたsiRNA組織内浸透型DDSの設計,
ファインケミカル : 調査・資料・報道・抄録, Vol.50, No.6, 29-34, 2021年6月.

(文献検索サイトへのリンク): ● CiNii @ 国立情報学研究所 (CRID): 1523106606071655040

(CiNii: 1523106606071655040) 金沢貴憲 :
核酸医薬における非侵襲的な投与ルートと DDS,
実験医学増刊号, Vol.39, 102-108, 2021年.

(文献検索サイトへのリンク): ● CiNii @ 国立情報学研究所 (CRID): 1010857593557611649

(CiNii: 1010857593557611649) 金沢貴憲 :
鼻-脳輸送機構を基盤とする中枢標的DDSナノキャリアの開発,
月刊ファインケミカル, Vol.50, 17-23, 2021年.

(文献検索サイトへのリンク): ● CiNii @ 国立情報学研究所 (CRID): 1010857593557611648

(CiNii: 1010857593557611648) 金沢貴憲 :
中枢神経系領域を標的とする薬物・核酸医薬のNose-to-Brainデリバリーに関する研究,
Drug Delivery System, Vol.35, No.5, 434-441, 2020年11月.

(キーワード): 医薬品情報学 (pharmaceutical information science)
(出版サイトへのリンク): ● Publication site (DOI): 10.2745/dds.35.434
(文献検索サイトへのリンク): ● CiNii @ 国立情報学研究所 (CRID): 1390850247499217280; ● Search Scopus @ Elsevier (DOI): 10.2745/dds.35.434

(DOI: 10.2745/dds.35.434, CiNii: 1390850247499217280) 鈴木豊史, 鈴木直人, 金沢貴憲 :
鼻から脳への薬物送達における輸送機構とナノシステムの役割,
オレオサイエンス, Vol.20, No.2, 61-69, 2020年.

(キーワード): nose-to-brain drug delivery / intranasal route / intranasal delivery / polymer nanomicelles
(出版サイトへのリンク): ● Publication site (DOI): 10.5650/oleoscience.20.61
(文献検索サイトへのリンク): ● CiNii @ 国立情報学研究所 (CRID): 1390846609803025152; ● Search Scopus @ Elsevier (DOI): 10.5650/oleoscience.20.61

(DOI: 10.5650/oleoscience.20.61, CiNii: 1390846609803025152) 鈴木直人, 金沢貴憲, 鈴木豊史 :
Nose-to-Brainデリバリーを指向した経鼻投与製剤の設計,
ファームテクジャパン, Vol.36, 128-132, 2020年. 高島由季, 茨木ひさ子, 金沢貴憲 :
皮膚疾患治療に向けたsiRNA送達システム,
Drug Delivery System, Vol.33, No.4, 285-292, 2018年9月.

(キーワード): 皮膚 (skin) / transdermal administration / siRNA, tight junction / atopic dermatitis
(出版サイトへのリンク): ● Publication site (DOI): 10.2745/dds.33.285
(文献検索サイトへのリンク): ● CiNii @ 国立情報学研究所 (CRID): 1390564238055076352; ● Search Scopus @ Elsevier (DOI): 10.2745/dds.33.285

(DOI: 10.2745/dds.33.285, CiNii: 1390564238055076352) 金沢貴憲 :
非侵襲的な脳内への薬物送達技術の開発と脳神経疾患治療への応用,
薬学雑誌, Vol.138, No.4, 443-450, 2018年4月.

(キーワード): nose-to-brain route / 薬物送達システム (drug delivery system) / polymer micelle / cell-penetrating peptide / siRNA delivery / brain/central nervous system disease
(出版サイトへのリンク): ● Publication site (DOI): 10.1248/yakushi.17-00179
(文献検索サイトへのリンク): ● CiNii @ 国立情報学研究所 (CRID): 1390001206216091904; ● Search Scopus @ Elsevier (DOI): 10.1248/yakushi.17-00179

(DOI: 10.1248/yakushi.17-00179, CiNii: 1390001206216091904) 金沢貴憲, 鈴木直人, 鈴木豊史 :
脳・中枢神経系疾患治療薬開発の鍵となるBBB介在性および非介在性の薬物送達システム,
バイオマテリアル-生体材料-, Vol.36, 214-219, 2018年.

(文献検索サイトへのリンク): ● CiNii @ 国立情報学研究所 (CRID): 1010566775532070528

(CiNii: 1010566775532070528) 金沢貴憲 :
Nose-to-Brainを基盤とする脳への核酸医薬DDS,
BIO Clinica, Vol.33, 54-57, 2018年.

(文献検索サイトへのリンク): ● CiNii @ 国立情報学研究所 (CRID): 1010282256944207488

(CiNii: 1010282256944207488) 金沢貴憲 :
高分子ミセルを基盤とする siRNA の全身およびNose-to-Brain DDS の開発,
Drug Delivery System, Vol.32, 2017年. Takanori KANAZAWA :
Brain delivery of small interfering ribonucleic acid and drugs through intranasal administration with nano-sized polymer micelles.,
Medical Devices : Evidence and Research, Vol.8, 57-64, Jan. 2015.

(要約): Recently, the development of effective strategies for enhancing drug delivery to the brain has been a topic of great interest in both clinical and pharmaceutical fields. In this review, we summarize our studies evaluating nose-to-brain delivery of drugs and small interfering ribonucleic acids in combination with cell-penetrating peptide-modified polymer micelles. Our findings show that the use of polymer micelles with surface modification with Tat peptide in the intranasal administration enables the non-invasive delivery of therapeutic agents to the brain by increasing the transfer of the administered drug or small interfering ribonucleic acid to the central nervous system from the nasal cavity.
(出版サイトへのリンク): ● Publication site (DOI): 10.2147/MDER.S70856
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 25610007; ● Summary page in Scopus @ Elsevier: 2-s2.0-84920528083

(DOI: 10.2147/MDER.S70856, PubMed: 25610007, Elsevier: Scopus) 金沢貴憲, 高島由季 :
細胞透過性ペプチド修飾ナノキャリアと経鼻投与を用いた非侵襲的な脳への核酸送達技術,
ファームテックジャパン, Vol.30, 1113-1118, 2014年. Hiroaki Okada, Ko Tanaka, Takaya Ogawa, Takanori KANAZAWA and Yuuki Takashima :
Cytoplasm-responsive delivery systems for siRNA using cell-penetrating peptide nanomicelles,
Journal of Drug Delivery Science and Technology, Vol.24, No.1, 3-11, 2014.

(出版サイトへのリンク): ● Publication site (DOI): 10.1016/S1773-2247(14)50001-9
(文献検索サイトへのリンク): ● Summary page in Scopus @ Elsevier: 2-s2.0-84894240911

(DOI: 10.1016/S1773-2247(14)50001-9, Elsevier: Scopus) 金沢貴憲, 高島由季 :
高分子ミセルをキャリアとする経鼻投与による脳への薬物・核酸デリバリー,
Drug Delivery System, Vol.28, No.4, 318-327, 2013年.

(キーワード): Intranasal brain delivery / micelles / cell penetrating peptide, brain tumor / siRNA delivery
(出版サイトへのリンク): ● Publication site (DOI): 10.2745/dds.28.318
(文献検索サイトへのリンク): ● CiNii @ 国立情報学研究所 (CRID): 1390001204641465088; ● Search Scopus @ Elsevier (DOI): 10.2745/dds.28.318

(DOI: 10.2745/dds.28.318, CiNii: 1390001204641465088) 高島由季, 金沢貴憲 :
siRNAの経皮デリバリー研究,
ファルマシア, Vol.49, No.5, 385-389, 2013年.

(出版サイトへのリンク): ● Publication site (DOI): 10.14894/faruawpsj.49.5_385
(文献検索サイトへのリンク): ● CiNii @ 国立情報学研究所 (CRID): 1390282679475522304; ● Search Scopus @ Elsevier (DOI): 10.14894/faruawpsj.49.5_385

(DOI: 10.14894/faruawpsj.49.5_385, CiNii: 1390282679475522304) 高島由季, 土屋智裕, 五十嵐祐子, 金沢貴憲, 岡田弘晃, Arto Urtti :
後眼部指向型核酸封入リポソーム点眼剤の設計,
薬学雑誌, Vol.132, No.12, 1365-1370, 2012年12月.

(キーワード): posterior eye segment / retinal pigment epithelial cell / リポソーム (liposomes) / nucleic acid delivery
(出版サイトへのリンク): ● Publication site (DOI): 10.1248/yakushi.12-00234-3
(文献検索サイトへのリンク): ● CiNii @ 国立情報学研究所 (CRID): 1390282681105573120; ● Search Scopus @ Elsevier (DOI): 10.1248/yakushi.12-00234-3

(DOI: 10.1248/yakushi.12-00234-3, CiNii: 1390282681105573120) Takanori KANAZAWA, Yuuki Takashima and Hiroaki Okada :
Vaginal DNA vaccination against infectious diseases transmitted through the vagina.,
Frontiers in Bioscience (Elite edition), Vol.4, No.7, 2340-2353, Jun. 2012.

(要約): There is an urgent need for the development of vaccines against genital virus infections that are transmitted through heterosexual intercourse, including the HIV and HPV. In general, the surface of female genital mucosa, including vaginal mucosa, is the most common site of initiation of these infections. Thus, it is becoming clear that successful vaccines must induce both cellular and humoral immune responses in both the local genital tract and systemically. We believe that a strong vaginal immune response could be obtained by inducing strong gene expression of antigen-coding DNA in the local targeted tissue. In order to improve transfection efficiency in the vagina, it is important that methods allowing breakthrough of the various barriers, such as the epithelial layer, cellular and nuclear membrane, are developed. Therefore, systems providing less invasive and more effective delivery into the subepithelial layer are required. In this review, we will introduce our studies into efficient vaginal DNA vaccination methods, focusing on the effects of the menstrual cycle, utilization of the combination of functional peptides, and use of a needle-free injector.
(キーワード): Drug Administration Routes / 女性 (female) / Humans / Sexually Transmitted Diseases / Vaccines, DNA / Vagina
(出版サイトへのリンク): ● Publication site (DOI): 10.2741/e546
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 22652641; ● Search Scopus @ Elsevier (PMID): 22652641; ● Search Scopus @ Elsevier (DOI): 10.2741/e546

(DOI: 10.2741/e546, PubMed: 22652641) 金沢貴憲, 松村悠, 高島由季, 岡田弘晃 :
SMEDDS技術による処方の標準化の試み,
ファインケミカル : 調査・資料・報道・抄録, Vol.39, No.7, 42-46, 2010年7月.

(文献検索サイトへのリンク): ● CiNii @ 国立情報学研究所 (CRID): 1521980704751136000

(CiNii: 1521980704751136000) 金沢貴憲, 高島由季, 岡田弘晃 :
徐放性マイクロスフェア型注射剤の開発によるsiRNA制がん剤の創薬,
Drug Delivery System, Vol.23, No.5, 544-552, 2008年.

(キーワード): small interfering RNA (siRNA) / chemical modification / poly (DL-lactic/glycolic acid)(PLGA) / sustained release microspheres / anti-tumor effect
(出版サイトへのリンク): ● Publication site (DOI): 10.2745/dds.23.544
(文献検索サイトへのリンク): ● CiNii @ 国立情報学研究所 (CRID): 1390282679617243392; ● Search Scopus @ Elsevier (DOI): 10.2745/dds.23.544

(DOI: 10.2745/dds.23.544, CiNii: 1390282679617243392) 金沢貴憲, 高島由季, 尾関哲也, 安藤利亮, 並木徳之, 岡田弘晃 :
医療薬学実務基礎実習へのグミ製剤調製実習の導入と学生の反応,
ファームテックジャパン, Vol.23, No.8, 1587-1591, 2007年.

(文献検索サイトへのリンク): ● CiNii @ 国立情報学研究所 (CRID): 1572824500743832320

(CiNii: 1572824500743832320)

講演・発表

Yuna Mano, Takayuki Terukina, Takanori KANAZAWA and Hiromu Kondo :
The Effect of Cholesterol Content and PEG Modification on Morphology of DOPC Nanoparticles Prepared by Microfluidic Device Method,
APSTJ Global Education Seminar 2023 1st, Online, Oct. 2023. Yuta Watanabe, Momoka Yamaguchi, Takanori KANAZAWA, Sumire Morino, Shingo Iioka, Naoki Dohi, Kenjirou Higashi, Hiromu Kondo and Tomohisa Ishikawa :
Treatment of hepatocytes with palmitic acid induces the release of extracellular vesicles with tropism to activated hepatic stellate cells,
日本薬物動態学会第38回年会第23回シトクロムP450国際会議国際合同大会, Shizuoka, Sep. 2023. Takayuki Oguma, Takanori KANAZAWA, Yukiko K. Kaneko, Ren Sato, Miku Serizawa, Akira Ooka, Momoka Yamaguchi, Yuuna Mano, Shingo Iioka, Tomohisa Ishikawa and Hiromu Kondo :
Effects of in vivo distribution kinetics and intrapancreatic islet distribution of Lipid nanoparticles by their phospholipid components and particle size,
日本薬物動態学会第38回年会第23回シトクロムP450国際会議国際合同大会, Shizuoka, Sep. 2023. Takayuki Terukina, Takanori KANAZAWA and Hiromu Kondo :
Characterization of the viscoelasticity of disintegrants by dynamic rheological analysis,
4th International Symposium on BA/BE of Oral Drug Products, 2022, Shiga, Nov. 2022. Takanori KANAZAWA, Mami Kaneko, Hisako Ibaraki, Yuuki Takashima, Toyofumi Suzuki and Yasuo Seta :
Observation of the siRNA delivery kinetics via nose-to-brain route combined with stearate- or polyethylene glycol-modified arginine-rich peptides using ex vivo fluorescent imaging,
The Oligonucleotide Therapeutics Society (OTS) Annual Meeting 2019, Munich, Oct. 2019. Takanori KANAZAWA, Nao Maruhana, Mayu Yamada, Takashi Udagawa, Naoto Suzuki and Toyofumi Suzuki :
Effects of surface charge and PEG modification of liposome on its quantitative distribution in the brain and spinal cord by nose-to-brain delivery,
Liposome Research Days (LRD) 2019, Sapporo, Sep. 2019. Takanori KANAZAWA, Takaki Niide, Masahide Kanari, Maito Higuchi, Takumi Kurano, Hisako Ibaraki, Yuuki Takashima, Toyofumi Suzuki and Yasuo Seta :
Therapeutic Effects of Cerebral Ischemia Reperfusion Injuries in Rats by Nose-to-Brain Delivery of Cyclosporine A-Loaded Polymer Micelles,
The Controlled Release Society (CRS) Annual Meeting & Exposition 2019, Valencia, Jul. 2019. Takanori KANAZAWA, Maito Higuchi, Takumi Kurano, Hisako Ibaraki, Naoto Suzuki, Yuuki Takashima, Toyofumi Suzuki and Yasuo Seta :
Therapeutic Effects Of Cerebral Ischemia Reperfusion Injuries In Rats By Nose-to-brain Delivery Of Anti TNF-alpha siRNA-loaded Polymer Micelles,
The CRS Annual Meeting & Exposition 2018, New York, Jul. 2018. Takanori KANAZAWA :
Nose-to-brain delivery of drug/siRNA with cell-penetrating peptide modified polymer micelles,
Drug Discovery & Therapy World Congress 2016, Boston, Aug. 2016. Takanori KANAZAWA :
Nose-to-brain delivery of drug/siRNA with nanocarriers,
APSTJ Global Education Seminar 2015-3rd, Shizuoka, Feb. 2016. 金沢貴憲, 白石俊介, 中田叡, 入山友輔, 大塚敬一朗, 茨木ひさ子, 高島由季 :
均一性の高いsiRNA搭載高分子微小ミセルの開発とその静脈投与によるがん・リウマチ治療効果,
日本薬剤学会第35年会, 金沢貴憲, 白石俊介, 中田叡, 入山友輔, 大塚敬一朗, 茨木ひさ子, 高島由季 :
核酸搭載高分子微小ナノミセルの開発と静脈投与によるがん・リウマチ治療,
日本核酸医薬学会第5回年会, 芹澤未来, 金沢貴憲, 金子雪子, 佐藤蓮, 大岡央, 山口桃生, 真野結奈, 飯岡真吾, 尾熊貴之, 照喜名孝之, 石川智久, 近藤啓 :
静脈投与による脂質ナノ粒子の膵島分布特性に及ぼすリン脂質および粒子径の影響,
日本病院薬剤師会東海ブロック・日本薬学会東海支部合同学術大会2023, 2023年11月. 吉田圭輝, 照喜名孝之, 金沢貴憲, 近藤啓 :
マイクロ流体デバイス法によるブロックコポリマーナノ粒子の調製と物性及び脳内移行性評価,
日本病院薬剤師会東海ブロック・日本薬学会東海支部合同学術大会2023, 2023年11月. 飯岡真吾, 金沢貴憲, 照喜名孝之, 近藤啓 :
ブロックコポリマー/塩基性ペプチドからなる共集合化ナノDDS 基盤技術開発への挑戦とNose-to-Brain への応用,
日本病院薬剤師会東海ブロック・日本薬学会東海支部合同学術大会2023, 2023年11月. 柴田涼吾, 金子雪子, 山口桃生, 森野純鈴, 金沢貴憲, 石川智久 :
植物由来エキソソーム様ナノ粒子が膵β細胞アポトーシスに及ぼす影響の検討,
日本病院薬剤師会東海ブロック・日本薬学会東海支部合同学術大会2023, 2023年11月. 森野純鈴, 山口桃生, 岡部磨幸, 河合佑美, 金子雪子, 柴田涼吾, 大岡央, 金沢貴憲, 石川智久 :
植物由来エキソソーム様ナノ粒子が肝星細胞の活性化制御および細胞への取り込みに及ぼす影響,
第44回生体膜と薬物の相互作用シンポジウム, 2023年10月. 佐藤蓮, 金子雪子, 金沢貴憲, 芹澤未来, 大岡央, 山口桃生, 真野結奈, 飯岡真吾, 尾熊貴之, 近藤啓, 石川智久 :
膵島に集積する脂質ナノ粒子の開発を目指したリン脂質の組成および粒子径の検討,
第44回生体膜と薬物の相互作用シンポジウム, 2023年10月. 柴田涼吾, 金子雪子, 山口桃生, 森野純鈴, 金沢貴憲, 石川智久 :
膵 β 細胞アポトーシスに対する植物由来エキソソーム様ナノ粒子の効果の検証,
次世代を担う若手のための創薬・医療薬理シンポジウム 2023, 2023年8月. 青木駿典, 金沢貴憲, 飯岡真吾, 照喜名孝之, 真栄城正寿, 渡慶次学, 近藤啓 :
ブロックコポリマー/機能性ペプチド共集合化ナノ粒子の調製と経鼻投与による脳脊髄への核酸DDSキャリアとしての有用性評価,
第39回日本DDS学会学術集会, 2023年7月. 真野結奈, 金沢貴憲, 芹澤未来, 東顕二郎, 照喜名孝之, 近藤啓 :
マイクロ流体デバイス法により調製したDOPCナノ粒子の形態に及ぼすコレステロール含量・PEG修飾の影響,
第39回日本DDS学会学術集会, 2023年7月. 岩木徹, 門柚里, 渡邊真衣, 森田祐子, 松本恒平, 照喜名孝之, 金沢貴憲, 近藤啓 :
3成分系からなるクルクミン固体分散体の調製と評価,
日本薬剤学会第38年会, 2023年5月. 須磨佳史, 照喜名孝之, 金沢貴憲, 近藤啓 :
遠心転動造粒における粒子径・水分率・粘弾性の関係,
日本薬剤学会第38年会, 2023年5月. 長内楓, 村本彩織, 照喜名孝之, 金沢貴憲, 近藤啓 :
テープ剤におけるSISブロック共重合体を用いた粘着層の物性に及ぼす流動パラフィンの影響,
日本薬剤学会第38年会, 2023年5月. 照喜名孝之, 武田真奈, 金沢貴憲, 近藤啓 :
コフォーマーがテオフィリン共結晶製剤物性に与える影響,
日本薬剤学会第38年会, 2023年5月. 近藤啓, 内山嘉稀, 照喜名孝之, 金沢貴憲 :
消化管粘膜付着性ナノファイバーシートによるBCS Class III化合物の吸収性改善,
日本薬剤学会第38年会, 2023年5月. 金沢貴憲 :
中枢を標的とする経鼻投与型ナノDDSの開発,
日本薬学会第143年会, 2023年3月. 岡部磨幸, 山口桃生, 大岡央, 森野純鈴, 柴田涼吾, 金沢貴憲, 金子雪子, 石川智久 :
肝星細胞の活性化に対する植物由来エキソソーム様ナノ粒子の作用解析,
日本薬学会第143回年会, 2023年3月. 岩木徹, 門柚里, 松本恒平, 照喜名孝之, 金沢貴憲, 近藤啓 :
高い過飽和維持能を示すクルクミン固体分散体の調製,
日本薬学会第143年会, 2023年3月. 金沢貴憲 :
Nose-to-BrainナノDDSの開発と脳・脊髄疾患治療への応用,
第96回日本薬理学会年会, 2022年12月. 岩木徹, 門柚里, 松本恒平, 照喜名孝之, 金沢貴憲, 近藤啓 :
経口吸収性を顕著に改善するクルクミン固体分散体の調製,
第39回製剤と粒子設計シンポジウム, 2022年11月. 飯岡真吾, 金沢貴憲, 吉田圭輝, 青木駿典, 照喜名孝之, 東顕二郎, 真栄城正寿, 渡慶次学, 近藤啓 :
PEGおよびPCL鎖分子量の異なるPEG-PCLブロックコポリマーからなるナノ粒子の物性およびNose-to-Brain移行性,
第17回ナノ・バイオメディカル学会大会, 2022年11月. 岩木徹, 門柚里, 松本恒平, 照喜名孝之, 金沢貴憲, 近藤啓 :
経口吸収性を顕著に改善するクルクミン固体分散体の調製,
日本薬物動態学会第37年会, 2022年11月. 金沢貴憲 :
CNS-targeted nanoDDS based on the nose-to-brain route(アジア4カ国合同シンポジウム),
日本薬物動態学会第37回年会, 2022年11月. 渡辺雄太, 山口桃生, 金沢貴憲, 森野純鈴, 飯岡真吾, 東顕二郎, 土肥直貴, 近藤啓, 石川智久 :
肝実質細胞由来EVの物性と肝星細胞への指向性に及ぼす脂肪酸暴露の影響,
日本病院薬剤師会東海ブロック・日本薬学会東海支部合同学術大会2022, 2022年11月. 富田裕也, 小野芳幸, 照喜名孝之, 金沢貴憲, 近藤啓 :
口腔内崩壊フィルム基剤の粘弾性とフィルム特性との関連性に関する検討,
日本病院薬剤師会東海ブロック・日本薬学会東海支部合同学術大会2022, 2022年11月. 堤圭伍, 照喜名孝之, 金沢貴憲, 近藤啓 :
製剤学的特性が人工膜における貼付剤からの薬物透過に及ぼす影響,
日本病院薬剤師会東海ブロック・日本薬学会東海支部合同学術大会2022, 2022年11月. 鈴木海羽, 瀬部卓之, 照喜名孝之, 金沢貴憲, 近藤啓 :
経口固形製剤の崩壊過程における動的粘弾性とテクスチャーとの関連性,
日本病院薬剤師会東海ブロック・日本薬学会東海支部合同学術大会2022, 2022年11月. 金沢貴憲, 茨木ひさ子, 高島由季, 近藤啓 :
組織浸透性核酸内封リポソームの開発と静脈投与後の腫瘍内浸透性および抗腫瘍効果の検証,
第43回生体膜と薬物の相互作用シンポジウム, 2022年10月. 金沢貴憲 :
核酸医薬の新たな投与部位・生体内送達ルートに着目した新規ナノDDSの開拓,
日本核酸医薬学会第7回年会, 2022年8月. 金沢貴憲, 山口桃生, 森野純鈴, 飯岡真吾, 土肥直貴, 石川智久, 近藤啓 :
肝実質細胞由来sEVの活性型肝星細胞への取り込みに及ぼす脂肪酸曝露の影響,
日本薬剤学会第37年会, 2022年5月. 金沢貴憲 :
中枢・胎盤を標的とする薬物送達システム研究,
第29回日本胎盤学会学術集会, 2021年11月. 金沢貴憲 :
Nose-to-Brainルートを基盤とする中枢標的DDS,
日本薬物動態学会第14回ショートコース, 2021年11月. 金沢貴憲 :
鼻腔-中枢輸送ルートを基盤とするDDSの最新知見と核酸医薬への応用,
核酸医薬シンポジウム2020, 2020年12月. 金沢貴憲 :
中枢神経系領域を標的とする薬物・核酸医薬のNose-to-Brainデリバリーに関する研究(奨励賞受賞講演),
第36回日本DDS学会学術集会, 2020年8月. 金沢貴憲 :
ナノ粒子を利用した Nose-to-Brain薬物送達研究の現状と将来展望,
第36回日本DDS学会学術集会, 2020年8月. 金沢貴憲, 浅見亜紀子, 仁藤裕也, 福田沙也伽, 宇田川崇, 藏野匠, 鈴木直人, 橋崎要, 小菅康弘, 鈴木豊史 :
細胞膜透過ペプチド修飾高分子ミセル併用経鼻投与による水溶性薬物の脊髄内分布ならびに筋委縮性側索硬化症に対する治療効果,
日本薬学会第140年会, 2020年3月. 金沢貴憲 :
鼻腔-脳の生理学的ルートを基盤とする中枢組織への非侵襲的な薬物・バイオ医薬デリバリー技術の開発,
第93回日本薬理学会年会, 2020年3月. 金沢貴憲 :
鼻-脳の潜在的ルートを基盤とする経鼻投与型中枢標的DDS,
第41回生体膜と薬物相互作用シンポジウム, 2019年10月. 金沢貴憲, 浅見亜紀子, 仁藤裕也, 飯岡真吾, 福田沙也伽, 宇田川崇, 福田光良, 藏野匠, 鈴木直人, 小菅康弘, 鈴木豊史 :
Tat修飾高分子ミセルを併用した経鼻投与によるBBB非透過性分子の中枢神経系内分布と脳・脊髄疾患治療,
第 28 回 DDS カンファランス, 2019年9月. 金沢貴憲 :
細胞透過性ペプチド修飾高分子ミセルを基盤としたNose-to-Brain DDSの開発,
第35回日本DDS学会学術集会, 2019年7月. 金沢貴憲 :
中枢領域を標的とする医薬品開発における Nose-to-Brain研究の現状とその将来展望,
第56回薬剤学懇談会研究討論会, 2019年6月. 金沢貴憲 :
中枢疾患を標的とする非侵襲的核酸医薬DDS技術,
日本薬剤学会第34年会, 2019年5月. 金沢貴憲 :
機能性ペプチドを基盤とする非侵襲的な核酸医薬DDSの開発(奨励賞受賞講演),
日本薬剤学会第34年会, 2019年5月. 金沢貴憲, 鈴木直人, 鈴木豊史 :
経鼻投与による薬物・バイオ医薬の脳内デリバリー動態と中枢疾患治療への応用,
日本薬剤学会第34年会, 2019年5月. 金沢貴憲, 鈴木直人, 鈴木豊史 :
中・高分子医薬のNose-to-Brainデリバリーによる中枢疾患治療,
日本薬学会139年会, 2019年3月. 金沢貴憲 :
Nose-to -Brain 経路を利用した中・高分子医薬の中枢デリバリー,
日本薬学会北海道支部主催・特別講演会 (北海道大学大学院薬学研究院共催), 2019年2月. 金沢貴憲, 福田光良, 鈴木直人, 鈴木豊史 :
BBB透過性および非透過性物質のマウス鼻腔内投与後の中枢移行性,
日本薬剤学会 DDS製剤臨床応用フォーカスグループ合宿討論会, 2018年12月. 金沢貴憲, 藏野匠, 樋口舞人, 茨木ひさ子, 高島由季, 鈴木豊史, 瀬田康生 :
抗TNF-α siRNA搭載細胞透過性ペプチド修飾高分子ミセルのNose-to-Brainデリバリーによる脳虚血再灌流障害治療,
日本核酸医薬学会第4回年会, 2018年7月. 金沢貴憲, 大場葵, 増山雄大, 山田茉由, 福田光良, 鈴木直人, 小菅康弘, 鈴木豊史 :
蛍光ex vivoイメージングによる種々のリポソームのNose-to-Brainデリバリーの観察,
第34回日本DDS学会学術集会, 2018年6月. 金沢貴憲, 尾熊貴之, 飯岡真吾, 日高裕太, 福田光良, 鈴木直人, 小菅康弘, 鈴木豊史 :
エバンスブルー結合アルブミンを用いたモデルタンパク質の経鼻投与による脳および脊髄移行性,
日本薬剤学会第33年会, 2018年5月. 金沢貴憲, 益子崇, 福田光良, 畑山真佑佳, 樋口優美, 鈴木直人, 木澤靖夫, 鈴木豊史 :
ナロキソン経鼻投与後の脳内移行性ならびに虚血再灌流障害マウスにおける脳保護効果,
日本薬学会第138年会, 2018年3月. 金沢貴憲, 高島由季 :
蛍光イメージングを用いた核酸医薬DDSのin vivoおよびex vivo動態評価,
第26回日本バイオイメージング学会学術集会, 2017年9月. 金沢貴憲 :
血液脳関門を介さないNose-to-Brainデリバリーを利用した薬物・核酸医薬による脳疾患治療,
第61回日本薬学会関東支部大会, 2017年9月. 金沢貴憲 :
Nose-to-Brainルートを介した脳・中枢神経系への核酸デリバリー戦略,
日本核酸医薬学会第3回年会, 2017年7月. 金沢貴憲 :
非侵襲的な脳内への薬物送達技術の開発と脳神経疾患治療への応用(奨励賞受賞講演),
第60回日本薬学会関東支部大会, 2016年9月. 金沢貴憲 :
経鼻投与を利用した非侵襲的な脳への薬物・バイオ医薬デリバリー,
第57回日本先天性代謝異常学会, 2015年11月. 金沢貴憲, 高島由季, 瀬田康生 :
DDS技術を利用した抗NF-κB siRNAによる免疫疾患治療,
日本薬学会第134年会, 2014年3月. 金沢貴憲 :
効率的な経膣粘膜DNAワクチンの確立に向けた新規遺伝子ベクターならびに至適投与方法の開発(Postdoctoral Presentation),
第37回日本薬剤学会製剤セミナー, 2013年7月. 高島由季, 金沢貴憲, 瀬田康生 :
経鼻投与による脳への薬物および核酸デリバリー,
日本薬学会第133年会, 2013年3月. 金沢貴憲 :
非侵襲的な脳送達システムの構築とその効果,
第3回ミトコンドリアとDDS, 2012年7月. 金沢貴憲, 高島由季, 岡田弘晃 :
効率的な経膣粘膜DNAワクチンの確立に向けた新規遺伝子ベクターならびに至適投与方法の開発(Postdoctoral Session),
第20回DDSカンファランス, 2011年9月. 金沢貴憲, 高島由季, 岡田弘晃 :
膣粘膜DNAワクチンのDDS,
第27回日本DDS学会, 2011年6月.

研究会・報告書: Takanori KANAZAWA, Yuuki Takashima and Hiroaki Okada :
Development of novel gene vector and dosing device for intravaginal DNA vaccine,
Progress in Drug Delivery System, Vol.20, 29-33, 金沢貴憲 :
Nose-to-Brain型ナノDDSによる脳脊髄への非侵襲的な核酸送達技術の開発,
徳島大学・九州大学BINDS合同シンポジウム, 2023年10月. 金沢貴憲 :
Nose-to-BrainナノDDSで拓く脳脊髄疾患の非侵襲的な核酸医薬治療,
徳島大学第9回BRIGHTシンポジウム, 2023年10月. 金沢貴憲 :
Nose-to-Brain型ナノDDSによる脳・脊髄への核酸デリバリー,
遺伝子・デリバリー研究会第21回夏季セミナー, 2023年8月. 金沢貴憲 :
核酸医薬におけるナノDDSと非侵襲的投与ルートの役割,
DDS/パッケージングセミナー，CPHI Japan 2023, 2023年4月. 金沢貴憲 :
核酸医薬におけるDDSの基礎から最前線まで,
情報機構技術セミナー, 2022年11月. 金沢貴憲 :
核酸医薬のユニークな投与部位・生体内送達ルートに着目したナノDDS,
千葉大学薬学研究院大学院講義「薬物学特論」, 2022年11月. 金沢貴憲 :
ニューモダリティ創薬の鍵を握る経鼻DDSの現状と展望,
立命館大学創剤・製剤技術研究コンソーシアム第3回研究会, 2022年10月. 金沢貴憲 :
核酸医薬におけるDDSと非侵襲的投与ルートの役割,
第24回インターフェックスジャパン専門技術セミナー, 2022年7月. 金沢貴憲 :
新たな生体内送達ルートに着目した薬物未到達領域へのナノDDSの開発,
徳島大学薬学部特別講演会, 2022年5月. 金沢貴憲 :
経鼻投与製剤の基礎と中枢標的DDS技術への応用,
日本BD主催Webinar, 2022年4月. 金沢貴憲 :
鼻から脳への(Nose-to-Brain)DDS,
第2回獣医DDS技術懇談会, 2022年4月. 金沢貴憲 :
核酸医薬におけるDDSの基礎から最前線まで,
情報機構技術セミナー, 2022年1月. 金沢貴憲 :
核酸医薬品開発におけるドラッグデリバリーシステムとナノ粒子技術の役割,
CMCリサーチウェビナー, 2021年11月. 金沢貴憲 :
中枢神経系領域を標的とする薬物・核酸のNose-to-Brain送達システム研究,
次世代薬理学セミナー2021, 2021年10月. 金沢貴憲 :
核酸医薬品開発におけるドラッグデリバリーシステムとナノ粒子技術の役割,
CMCリサーチウェビナー, 2021年9月. 金沢貴憲 :
核酸医薬におけるDDSの基礎から最前線まで,
情報機構技術セミナー, 2021年7月. 金沢貴憲 :
鼻腔-中枢の生理学的ルートを基盤とした中枢神経系への薬物・核酸デリバリー,
国際医薬品開発展2021, 2021年4月. 金沢貴憲 :
核酸医薬におけるDDSの基礎から最前線まで,
情報機構技術セミナー, 2021年3月. 金沢貴憲 :
経鼻投与製剤の基礎とNose-to-Brain研究,
第27回シミック製剤技術アカデミー/APSTJ製剤技術伝承講習会, 2021年3月. 金沢貴憲 :
中枢神経系疾患を標的とする多様な創薬モダリティと薬物送達システム研究,
岐阜薬科大学大学院特別講義, 2020年12月. 金沢貴憲 :
脊髄に薬物・中分子薬を届ける経鼻送達ナノカプセル技術,
JST ライフイノベーション新技術説明会, 2020年10月. 金沢貴憲 :
核酸医薬におけるDDSの基礎から最前線まで,
情報機構技術セミナー, 2020年9月. 鈴木直人, 金沢貴憲, 鈴木豊史 :
連載 DDSの「ちょっとした」技術・知識第5回: 経鼻投与,
Drug Delivery System, Vol.35, 2020年. 金沢貴憲 :
中枢神経系疾患を標的とする医薬品開発におけるNose-to-Brain DDS研究の現状と課題,
武田薬品工業株式会社ファーマシューティカルサイエンス講演会, 2019年11月. 金沢貴憲 :
鼻-脳の生理学的ルートを基盤とする中枢領域への経鼻DDSの最前線,
岩手医科大学薬学部セミナー, 2019年10月. 金沢貴憲 :
中枢疾患を標的とする医薬品開発におけるDDSの役割-Nose-to-Brainへの期待と課題,
田辺三菱株式会社社内講演会, 2019年10月. 金沢貴憲 :
Nose-to-Brain経路を利用した中枢への薬物・バイオ薬送達システム,
京都大学医学部脳神経内科セミナー, 2018年9月. 鈴木豊史, 金沢貴憲, 鈴木直人 :
血液脳関門を迂回する鼻から脳への薬物送達に適した鼻腔内製剤の開発を目指して,
製剤機械技術会誌, Vol.27, 216-221, 2018年. 金沢貴憲 :
健康・医療に貢献する真の製剤・DDS 技術の開発を目指して,
薬剤学, Vol.76, 150-155, 2016年. 金沢貴憲 :
第32回日本DDS学会学術集会印象記,
Drug Delivery System, Vol.31, 376-377, 2016年. 金沢貴憲 :
ノースイースタン大学での留学生活,
製剤機械技術学会誌, Vol.24, 331-333, 2015年. 金沢貴憲 :
39th Annual Meeting and Exposition of the Controlled Release Society参加報告,
薬剤学, Vol.72, 368, 2012年. 金沢貴憲 :
37th Annual Meeting and Exposition of the Controlled Release Society参加報告,
薬剤学, Vol.70, 2010年. 金沢貴憲 :
幹細胞の脳への送達は経鼻投与によっても可能, トピックス,
ファルマシア, Vol.46, No.354, 2010年. Ogawa Takaya, Takanori KANAZAWA, Yumiko Suda, Yuuki Takashima, Tsunehiko Fukuda and Hiroaki Okada :
Multifunctional peptide gene vector: Design and evaluation of disulfide cross-linked oligo arginine,
Peptide Science 2008, 77-80, 2008. 金沢貴憲 :
2007 AAPS Annual Meeting and Exposition参加報告,
薬剤学, Vol.68, 2008年.

特許: Takanori KANAZAWA, Y Takashima, H Ibaraki, Y Iriyama and K Otsuka : COMPOSITION FOR DELIVERING NUCLEIC ACID AND NUCLEIC ACID - CONTAINING COMPOSITION, US11345914 (May 2022). 金沢貴憲, 飯岡真吾, 近藤啓 : 核酸送達用組成物及び核酸含有組成物, 特願2023- 106324 (2023年6月), . 金沢貴憲, 金子雪子 : 脂質ナノ粒子, 特願2023-094594 (2023年6月), . 金沢貴憲, Y Kosuge, H Miyagishi, N Suzuki : 薬物送達用組成物および医薬組成物, 特願PCT/JP2020/018512 (2020年5月), . 金沢貴憲, 小菅康弘, 宮岸寛子, 鈴木直人 : 薬物送達用組成物および医薬組成物, 特願2019-115688 (2019年6月), 特許第7211603号 (2023年1月). 金沢貴憲, Y Takashima, H Ibaraki, Y Iriyama, K Otsuka : 核酸送達用組成物及び核酸含有組成物, 特願PCT/JP/2018/026199 (2018年7月), . 金沢貴憲, 高島由季, 茨木ひさ子, 入山祐輔, 大塚敬一郎 : 核酸送達用組成物及び核酸含有組成物, 特願2017-135547 (2017年7月), 特許第7246730号 (2023年3月). 金沢貴憲, Y Seta, H Okada, T Ohogi, T Hamasaki, T Mizutani : NF-κB RelA遺伝子の発現抑制剤, アレルギー性皮膚炎用医薬, およびその用途, 特願PCT/JP2014/062686 (2014年3月), . 金沢貴憲, 瀬田康生, 岡田弘晃, 大木忠明, 濱崎智洋, 水谷隆之 : NF-κB RelA遺伝子の発現抑制剤, アレルギー性皮膚炎用医薬, およびその用途, 特願2013 042237 (2013年3月), . 金沢貴憲, H Okada : オリゴ核酸組成物及び抗アレルギー剤, 特願PCT/JP2012/051916 (2012年1月), . 金沢貴憲, 岡田弘晃 : オリゴ核酸組成物及び抗アレルギー剤, 特願2011-018640 (2011年1月), .
作品: 研究者総覧に該当データはありませんでした。
補助金・競争的資金: 脳内病態伝播拠点標的RNA送達Nose-to-Brainミセル開発と脳神経ゲノム編集治療基盤構築 (研究課題/領域番号: 23K28433 )
脳内病態伝播拠点標的RNA送達Nose-to-Brainミセル開発と脳神経ゲノム編集治療基盤構築 (研究課題/領域番号: 23H03744 )
二重標的Nose-to-Brainミセルによる脳感染神経特異的RNA送達への挑戦 (研究課題/領域番号: 22K19921 )
経鼻投与型核酸搭載ナノバブルの開発と中枢神経系疾患の超音波治療システムの基盤構築 (研究課題/領域番号: 22H03978 )
薬物放出速度の持続制御が可能な非晶質固体分散体ナノファイバー製剤技術基盤の確立 (研究課題/領域番号: 21K06516 )
鼻－脳輸送機構に基づく核酸送達ナノDDSの開発とグリア標的治療への応用展開 (研究課題/領域番号: 20H04537 )
脳神経系希少疾患治療を目指した経鼻投与による脳内バイオ医薬デリバリー戦略の構築 (研究課題/領域番号: 17K08249 )
経鼻投与型機能性ペプチド修飾神経指向性ナノキャリアの開発と脳神経疾患治療への応用 (研究課題/領域番号: 25870767 )
機能性ペプチドを用いたアトピー治療用 siRNA の皮内送達システム構築と経皮製剤化 (研究課題/領域番号: 22790049 )
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専門分野・研究分野: ナノテク・材料 (Nanotechnology/Materials) [ナノ材料科学 (Nanomaterials)]
ライフサイエンス (Life sciences) [医療薬学 (Clinical pharmacy)]
ライフサイエンス (Life sciences) [生体材料学 (Biomaterials)]
ライフサイエンス (Life sciences) [薬系分析、物理化学 (Pharmaceuticals - analytical and physicochemistry)]
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Ｊグローバル

Jグローバル最終確認日: 2024/5/18 01:05
氏名（漢字）: 金沢貴憲
氏名（フリガナ）: カナザワタカノリ
氏名（英字）: Kanazawa Takanori
所属機関: 徳島大学教授

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researchmap最終確認日: 2024/5/19 01:07
氏名（漢字）: 金沢貴憲
氏名（フリガナ）: カナザワタカノリ
氏名（英字）: Kanazawa Takanori
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登録日時: 2011/1/12 00:00
更新日時: 2024/4/11 20:23
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所属: 徳島大学
部署: 大学院医歯薬学研究部(薬学域）
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研究者番号: 60434015

所属（現在）: 2024/4/1 : 徳島大学, 大学院医歯薬学研究部(薬学域), 教授

所属（過去の研究課題 情報に基づく）*注記: 2024/4/1 : 徳島大学, 大学院医歯薬学研究部(薬学域), 教授
2020/4/1 – 2023/4/1 : 静岡県立大学, 薬学部, 准教授
2017/4/1 – 2019/4/1 : 日本大学, 薬学部, 講師
2010/4/1 – 2015/4/1 : 東京薬科大学, 薬学部, 助教

審査区分/研究分野

研究代表者

生物系 / 医歯薬学 / 薬学 / 物理系薬学
生物系 / 医歯薬学 / 薬学 / 医療系薬学 / 生物系 / 医歯薬学 / 薬学 / 物理系薬学
小区分90120:生体材料学関連
中区分90:人間医工学およびその関連分野

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小区分47020:薬系分析および物理化学関連
小区分90130:医用システム関連

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siRNA / 機能性ペプチド / AT1002 / ハイドロゲル / アトピー性皮膚炎 / 核酸DDS / RelA / 液晶製剤 / セリシン / Re1A / 経皮製剤 / タイトジャンクション / 細胞透過性ペプチド / 脳デリバリー / Nose-to-Brain / 高分子ミセル / ナノキャリア / 核酸デリバリー / 脳内デリバリー / 脳虚血再灌流障害 / 脳血管障害 / 神経細胞 / DDS / 核酸 / 脳 / 経鼻投与 / 膜透過性ペプチド / ナノミセル / バイオ医薬 / 筋萎縮性側索硬化症 / ドラッグデリバリー / 中枢神経系疾患治療 / ALS / リポソーム / 水溶性高分子 / Nose-to-brain / 脳内薬物動態 / 希少疾患 / ナノ粒子 / グリア標的治療 / 多成分集合型ナノ粒子 / マイクロ流体デバイス / ミクログリア / 脂質材料 / 海馬 / 脂質様材料 / 共集合化ナノ粒子 / RNA送達 / 神経変性疾患 / ゲノム編集 / 嗅球 / 脳幹 / 二重標的ミセル / ウイルス感染

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ナノファイバー / 難溶解性薬物 / 非晶質固体分散体 / 放出制御製剤 / 電界紡糸 / 放出制御 / レオロジー / ナノバブル / 経鼻投与 / 超音波 / 脳 / マイクロ流体技術 / 低周波超音波

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