薬剤学研究室

研究テーマ

薬剤学研究室では、薬剤の有効で安全な投与法とその評価について、以下の研究を行っています。

(1）薬物内封ナノ粒子製剤の設計・最適化を目指した薬剤学的研究
　・非イオン性界面活性剤を構成成分としたリポソーム様ナノ粒子の調製とその機能評価
　・難水溶性薬物のエマルション製剤化とその機能評価
　・血管内皮細胞を標的とした新規がん化学療法の構築を目指した基礎的検討

(2）エピジェネティック修飾薬を用いた新規がん薬物療法の開発を目指した薬剤学的研究
　・エピジェネティック修飾薬を用いた新規併用療法の開発を目指した基礎的検討
　・エピジェネティック修飾薬の化合物安定性の向上を目指したナノ粒子の調製とその機能評価

(3）細胞のがん指向性を利用した新規抗がん剤送達システムの開発を目指した薬剤学的研究
　・間葉系幹細胞やマクロファージに抗がん剤内封ナノ粒子を結合させるための技術構築
　・細胞−リポソーム結合体の体内動態特性、および抗腫瘍効果の評価
　

スタッフ

大河原 賢一 教授

担当科目：薬物動態学I　臨床薬剤学I・II　薬剤学・製剤学実習　薬剤学特論（大学院） 臨床薬剤学特論（大学院）
学位：博士 (薬学)

所属学会：日本薬学会、日本薬物動態学会、日本薬剤学会、日本DDS学会 等
受賞歴：平成19年度 日本薬学会 中国四国支部 奨励賞　平成23年度 日本薬剤学会 奨励賞等

細川 美香 講師

担当科目：薬物動態学Ⅱ　臨床薬剤学Ⅱ　薬剤学・製剤学実習　薬剤学特論（大学院） 臨床薬剤学特論（大学院）
学位：博士 (薬学)

所属学会：日本薬学会、日本薬物動態学会、日本薬剤学会、日本医療薬学会 等

河野 裕允 講師

担当科目：薬物動態学I　薬剤学・製剤学実習　薬剤学特論（大学院） 臨床薬剤学特論（大学院）
学位：博士 (薬学)

所属学会：日本薬学会、日本薬剤学会、日本DDS学会、日本癌学会 等
受賞歴：2021年度 日本薬学会関西支部 奨励賞

研究成果

【論文】
Hosokawa M, Ito S, Noda K, Kono Y, Ogawara K.
Preparation and evaluation of paclitaxel-loaded PEGylated niosomes composed of sorbitan esters.
Biol Pharm Bull. Accepted.

Kono Y, Uesugi N, Saegusa M, Onishi K, Hosokawa M, Ogawara K.
Suppression of phagocytic activity leads to the efficient surface modification of macrophages with liposomes for developing a biomimetic drug delivery system
Biol Pharm Bull. 46, 1347-1351 (2023).

Hosokawa M, Tetsumoto S, Yasui M, Kono Y, Ogawara K.
3-deazaneplanocin A, a histone methyltransferase inhibitor, improved the chemoresistance induced under hypoxia in melanoma cells
Biochem Biophys Res Commun. 677, 26-30 (2023).

Kono Y, Kamino R, Hirabayashi S, Kishimoto T, Kanbara H, Danjo S, Hosokawa M, Ogawara K.
Efficient liposome loading onto surface of mesenchymal stem cells via electrostatic interactions for tumor-targeted drug delivery
Biomedicines, 11, 558 (2023).
本研究成果は、大学HPにてプレスリリースを配信しております。
https://www.kobepharma-u.ac.jp/news/006360.html

Tamer S*, Kono Y*, Higaki K, Kimura T, Ogawara K.
In vivo distribution characteristics and anti-tumor effects of doxorubicin encapsulated in PEG-modified niosomes in solid tumor-bearing mice
J Drug Deliv Sci Technol, 80, 104122 (2023).
*These authors contributed equally to this work.

Eguchi M, Hirata S, Ishigami I, Shuwari N, Ono R, Tachibana M, Tanuma M, Kasai A, Hashimoto N, Ogawara K, Mizuguchi H, Sakurai F.
Pre-treatment of oncolytic reovirus improves tumor disposition of PEG-liposomes
Journal of Controlled Release, 354, 35-44 (2023).

Tanaka H, Ochii Y, Moroto Y, Hirata D, Ibaraki T, Ogawara KI.
Nanocrystal Preparation of Poorly Water-Soluble Drugs with Low Metal Contamination Using Optimized Bead Milling Technology
Pharmaceutics, 14, 2633 (2022).

Maruyama M, Nishida Y, Tanaka H, Minami T, Ogawara K, Higaki K.
Analysis of Absorption Enhancing Mechanisms for Combinatorial Use of Spermine with Sodium Taurocholate in Caco-2 Cells
Eur J Pharm Biopharm, 180, 332-343 (2022).

Munekane M, Kosugi A, Yamasaki M, Watanabe Y, Kannaka K,
Sano K, Yamasaki T, Ogawara KI, Mukai T.
Biodistribution study of indium-111-labeled PEGylated niosomes as novel drug carriers for tumor-targeting
J Drug Deliv Sci Technol, 75, 103648, (2022).

Kono Y, Kajita H, Okada T, Nakagawa R, Fujita T, Konishi S.
Mesenchymal stem cells promote IL-6 secretion and suppress the gene expression of proinflammatory cytokines in contractile C2C12 myotubes
Biol Pharm Bull, 45, 962-967 (2022).

Nakashima S, Iwamoto T, Takanashi M, Ogawara KI, Maruyama M, Higaki K.
Effect of Excessive Serotonin on Pharmacokinetics of Cephalexin after Oral Administration: Studies with Serotonin-Excessive Model Rats
Pharm Res, 39, 2163-2178 (2022).

Kono Y, Fushimi A, Yoshizawa Y, Higaki K, Ogawara KI.
Effects of particle size and release property of paclitaxel-loaded nanoparticles on their peritoneal retention and therapeutic efficacy against mouse malignant ascites
Int J Pharm, 623, 121904 (2022).

Tanaka H, Ochii Y, Moroto Y, Hirata D, Ibaraki T, Ogawara KI.
Optimization of Milling Parameters for Low Metal Contamination in Bead Milling Technology
BPB Reports, 5, 45-49 (2022)

Tanaka S, Hosokawa M, Tatsumi A, Asaumi S, Imai R, Ogawara KI.
Improvement of Resistance to Oxaliplatin by Vorinostat in Human Colorectal Cancer Cells through Inhibition of Nrf2 Nuclear Translocation
Biochem. Biophys. Res. Commun. 607, 9-14 (2022)

Maruyama M, Tojo H, Toi K, Ienaka Y, Hyodo K, Kikuchi H, Ogawara KI, Higaki K.
Effect of doxorubicin release rate from polyethylene glycol-modified liposome on anti-tumor activity in B16-BL6 tumor-bearing mice
J. Pharm. Sci. 111, 293-297 (2022)

Iida H, Komagata T, Tanaka H, Nagasawa R, Nishio T, SHono T, Kitagawa J, Ogawara K, Shinozaki K, Seki A, Bruce M, Ohno T.
Novel Platform for Predicting Drug Effects in Patients with Acromegaly:
Translational Exposure?Response Evaluation of Growth Hormone-Inhibitory
Effect of Octreotide Following Growth Hormone-Releasing Hormone Stimulation
J. Pharmacol. Exp. Ther. 379, 400-408 (2021)

Mukai H, Takanashi M, Ogawara K, Maruyama M, Higaki K.
Possible regulation of P-glycoprotein function by adrenergic agonists in a
vascular-luminal perfused preparation of small intestine
J. Pharm. Sci. 110, 3889-3895 (2021)

Hosokawa M, Seiki R, Iwakawa S, Ogawara KI.
Combination of azacytidine and curcumin is a potential alternative in decitabine-resistant colorectal cancer cells with attenuated deoxycytidine kinase
Biochem. Biophys. Res. Commun. 578, 157-162 (2021)

Minamisakamoto T, Nishiguchi S, Hashimoto K, Ogawara K, Maruyama M, Higaki K.
Sequential administration of PEG-Span 80 niosome enhances anti-tumor effect of doxorubicin-containing PEG liposome
Eur. J. Pharm. Biopharm. 169, 20-28 (2021)

Kono Y, Takegaki J, Ohba T, Matsuda K, Negoro R, Fujita S, Fujita T.
Magnetization of mesenchymal stem cells using magnetic liposomes enhances their retention and immunomodulatory efficacy in mouse inflamed skeletal muscle
Int. J. Pharm. 596, 120298 (2021).

Tanaka S, Hosokawa M, Miyamoto T, Nakagawa A, Haruna M, Ueda K, Iwakawa S, Ogawara KI
miR-33a-5p in Small Extracellular Vesicles as Non-invasive Biomarker for Oxaliplatin Sensitivity in Human Colorectal Cancer Cells
Biochem. Biophys. Rep. 26, 100996 (2021)

Okawa S, Sumimoto S, Masuda K, Ogawara K, Maruyama M, Higaki K
Improvement of lipid solubility and oral bioavailability of a poorly water and poorly lipid-soluble drug, rebamipide, by utilizing its counter ion and SNEDDS preparation
Eur. J. Pharm. Sci. 159, 105721 (2021).

Kono Y, Miyamoto A, Hiraoka S, Negoro R, Fujita T.
Mesenchymal stem cells alter the inflammatory response of C2C12 mouse skeletal muscle cells
Biol. Pharm. Bull. 43, 1785-1791 (2020)

Tanaka H, Ochii Y, Moroto Y, Ibaraki T, Ogawara K
Development of novel bead milling technology with less metal contamination by pH optimization of the suspension medium
Chem. Pharm. Bull. 69, 81-85 (2020)

Hosokawa M, Goto K, Tanaka S, Ueda K, Iwakawa S, Ogawara KI
Optimization of analytical conditions for hydrophilic nucleic acids using mixed-mode and reversed-phase pentabromobenzyl columns
Chem. Pharm. Bull. 68, 1-6 (2020).

Iida H, Fujikawa R, Kozaki R, Harada R, Hosokawa Y, Ogawara K, Ohno T
Pharmacokinetic-Pharmacodynamic-Efficacy Modeling of ONO-7579, a Novel Pan-TRK Inhibitor, in a Murine Xenograft Tumor Model
J. Pharmacol. Exp. Ther. 373, 361-369 (2020).

Ueda K, Nakamura T, Tanaka S, Hosokawa M, Iwakawa S, Ogawara KI
Numerical analysis of apparent decitabine uptake in HCT116 cells: Incorporation of a bidirectional first-order kinetic parameter for ENT1 transport and Michaelis-Menten parameters for subsequent phosphorylation
Drug Metab. Pharmacokinet. 35, 124-130 (2020)

Hosokawa M, Tanaka S, Ueda K, Iwakawa S, Ogawara KI
Decitabine exerted synergistic effects with oxaliplatin in colorectal cancer cells intrinsic resistance to decitabine
Biochem. Biophys. Res. Commun. 509, 249-254 (2019)

Ueda K, Masuda A, Fukuda M, Tanaka S, Hosokawa M, Iwakawa S
Monophosphorylation by deoxycytidine kinase affects apparent cellular uptake of decitabine in HCT116 colon cancer cells
Drug Metab. Pharmacokinet. 32, 301-310 (2017)

Hosokawa M, Tanaka S, Ueda K, Iwakawa S
Different schedule-dependent effects of epigenetic modifiers on cytotoxicity by anticancer drugs in colorectal cancer cells
Biol. Pharm. Bull. 40, 2199-2204 (2017).

Tanaka S, Hosokawa M, Matsumura J, Matsubara E, Ueda K, Iwakawa S
Effects of zebularine on invasion activity and intracellular expression level of let-7b in colorectal cancer cells
Biol. Pharm. Bull. 40,1320-1325 (2017)

Masumoto N, Otsuki H, Iwakawa S, Inada S, Goya K, Sho H, Kurebayashi S, Hashimoto K, Koga M
Effect of alogliptin on the ratio of glycated albumin to HbA1c in patients with type 2 diabetes mellitus
Diabetol. Int. 8, 212-217 (2017)　

Masumoto N, Otsuki H, Iwakawa S, Koga M
Usefulness of glycated albumin in decisions regarding the discontinuation of a diabetic drug and factors associated with poor glycemic control following discontinuation in patients with type 2 diabetes mellitus
Diabetol. Int. 8, 39-44 (2017)　

Tsunashima D, Yamashita K, Ogawara K, Sako K, Hakomori T, Higaki K
Development of extended release solid dispersion granules of tacrolimus: Evaluation of release mechanism and human oral bioavailability
J. Pharm. Pharmacol. 69, 1697-1706 (2017)

Ogawara K, Fukuoka Y, Yoshizawa Y, Kimura T, Higaki K
Development of safe and potent O/W emulsion of paclitaxel to treat peritoneal dissemination
J. Pharm. Sci. 106, 1143-1148 (2017)

【総説】
大河原賢一
敵を知る：がんの多面的な理解に基づいた新規治療戦略構築を目指して
製剤機械技術学会誌, 29, 104-108 (2020)

Ogawara K and Higaki K.
Nanoparticle-Based Photodynamic Therapy: Current Status and Future Application to Improve Outcomes of Cancer Treatment
Chem. Pharm. Bull. 65, 637-641 (2017)

【著書】
大河原　賢一
ニオソームを利用した抗がん剤の新規デリバリーシステムの設計と開発、技術情報協会、新規モダリティ医薬品のための新しいDDS技術と製剤化、291-296 (2023)

大河原　賢一
ニオソームの体内動態評価法、技術情報協会、新規モダリティ医薬品のための新しいDDS技術と製剤化、505-509 (2023)

田中章太、大河原　賢一
次世代がん診断（マイクロRNA）、南山堂、図解　腫瘍薬学、川西正祐、賀川義之、大井一弥 編 173-177 (2020)

受賞