Ternary Complex of Plasmid DNA with Protamine and γ-Polyglutamic Acid for Biocompatible Gene Delivery System
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概要
- 論文の詳細を見る
The purpose of the present study was to investigate the usefulness of the ternary complex with protamine and γ-polyglutamic acid (γ-PGA), which are biodegradable materials for foods and medical products, as a safe gene delivery vector. We formed cationic binary complexes (plasmid DNA (pDNA)/protamine complexes) with high transfection efficiency. The binary complex showed slight toxicity probably related to its total cationic charge. Then, we formed ternary complexes (pDNA/protamine/γ-PGA complexes) by addition of anionic polymer, γ-PGA, and they showed no cytotoxicity. The transfection efficiency of the pDNA/protamine/γ-PGA complexes was as high as that of the pDNA/protamine complexes, although their zeta potentials were different. Inhibition study of the gene expressions in B16-F10 cells suggested that pDNA/protamine complexes were taken up by caveolae-mediated endocytosis and macropinocytosis. On the other hand, pDNA/protamine/γ-PGA complexes were taken up by clathrin-mediated endocytosis and macropinocytosis. Thus, we succeeded in developing the ternary complex as a safe gene delivery vector with biocompatible materials.
- 公益社団法人 日本薬学会の論文
著者
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Nakagawa Hiroo
Department Of Hospital Pharmacy Nagasaki University Hospital Of Medicine And Dentistry
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KODAMA Yukinobu
Department of Clinical Pharmacy, Graduate School of Biomedical Sciences, Nagasaki University
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Sasaki Hitoshi
Department Of Basic Pharmaceutics Faculty Of Pharmaceutical Sciences Kyoto University
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Muro Takahiro
Department Of Pharmacy Iizuka Hospital:pharmaceutical Sciences Fukuoka University Graduate School
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Kitahara Takashi
Department Of Breast Oncology Cancer Institute Hospital Of Japanese Foundation For Cancer Research
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Honda Masayuki
Division of Medical Informatics, Nagasaki University Hospital
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Nakamura Tadahiro
Department of Hospital Pharmacy, Nagasaki University Hospital
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Kurosaki Tomoaki
Department of Drug Delivery Research, Graduate School of Pharmaceutical Sciences, Kyoto University
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Higuchi Norihide
Department of Drug Delivery Research, Graduate School of Pharmaceutical Sciences, Kyoto University
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Kanda Kosuke
Department of Hospital Pharmacy, Nagasaki University Hospital
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Imamura Masanobu
Department of Hospital Pharmacy, Nagasaki University Hospital
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Muro Takahiro
Department of Hospital Pharmacy, Nagasaki University Hospital
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