Increased Gene Expression by Cationic Liposomes (TFL-3) in Lung Metastases Following Intravenous Injection(Biopharmacy)
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概要
- 論文の詳細を見る
We recently showed that size, not surface charge, is a major determinant of the in vitro lipofection efficiency of pDNA/TFL-3 complex (lipoplex), even in the presence of serum. In this study, the effect of lipoplex size as a result of interaction with serum proteins on in vitro lipofection and the relationship of this with in vivo lipofection was examined in a murine lung metastasis model. As previously described, the pDNA to lipid ratio (P/L ratio) affected both the size and zeta potential of the lipoplex. In vitro studies also indicated that transgene expression in B16BL6 cells was largely dependent on the size of the lipoplex, both in the absence or presence (50% (v/v)) of serum. An in vivo lipofection experiment showed that predominant gene expression in lungs occurred only in tumor-bearing mice, not in normal mice. Based on the in vitro study, this tumor-related gene expression was not related to lipoplex size in the presence of serum (50% (v/v)), suggesting that the size alteration, as the result of interactions with serum proteins in the blood stream may not play an important role in the case of systemic injections. In addition, the efficient gene expression in tumor-bearing lung was not related to the progression of lung metastases. The area-specific gene expression in tumor-bearing lungs, which was largely dependent on the P/L ratio of the lipoplexes, was observed by fluorescent microscopy. Although the underlying mechanism for the area-specific transgene expression is not clear, it may be related to the interaction of lipoplexes with tumor cells, vascular endothelial cells under angiogenesis and normal cells in the lungs. The possibility that TFL-3 is a useful utility to the targeted delivery of pDNA to lungs and tumor-related lipofection is demonstrated. This result suggests that area-specific gene expression in lung metastases may be achieved by controlling the physicochemical properties of the lipoplex, i.e. the P/L ratio.
- 公益社団法人日本薬学会の論文
- 2005-04-01
著者
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Ishida Tatsuhiro
Department of Pharmacokinetics and Biopharmaceutics, Subdivision of Biopharmaceutical Sciences, Inst
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Kiwada Hiroshi
Department of Pharmacokinetics and Biopharmaceutics, Subdivision of Biopharmaceutical Sciences, Inst
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Kiwada Hiroshi
徳島大学 ヘルスバイオサイエンス研究部薬物動態制御学
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Kiwada Hiroshi
Department Of Pharmacokinetics And Biopharmaceutics Subdivision Of Biopharmaceutical Sciences Instit
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Kiwada Hiroshi
Faculty Of Pharmaceutifal Sciences The University Of Tokushima
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OKU Naoto
Department of Radiobiochemistry, School of Pharmaceutical Sciences, University of Shizuoka
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Oku Naoto
タイ
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Kamada Haruhiko
医薬基盤研究所 創薬プロテオミクスプロジェクト
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Kiwada Hiroshi
Department Of Pharmacokinetics And Biopharmaceutics Faculty Of Pharmaceutical Sciences The Universit
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Kamiya Hiroyuki
Lab. For Molecular Design Of Pharmaceutics Fac. Of Pharmaceutical Sciences Hokkaido Univ.
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Oku N
Department Of Radiobiochemistry School Of Pharmaceutical Sicences University Of Shizuoka
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Oku Naoto
Department Of Medical Biochemistry And Coe Program In The 21st Century University Of Shizuoka School
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Kamada Hitoshi
Institute For Life Support Technology Yamagata Promotional Organization For Industrial Technology
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LI Wenhao
Department of Pharmacokinetics and Biopharmaceutics, Faculty of Pharmaceutical Sciences, The Univers
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OKADA Yurie
Department of Pharmacokinetics and Biopharmaceutics, Faculty of Pharmaceutical Sciences, The Univers
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Li Wenhao
Department Of Pharmacokinetics And Biopharmaceutics Faculty Of Pharmaceutical Sciences The Universit
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Okada Yurie
Department Of Pharmacokinetics And Biopharmaceutics Faculty Of Pharmaceutical Sciences The Universit
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Ishida Tatsuhiro
Dep. Of Pharmacokinetics And Biopharmaceutics Subdivision Of Biopharmaceutical Sciences Inst. Of Hea
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Ishida Tatsuhiro
Department Of Pharmacokinetics And Biopharmaceutics Subdivision Of Biopharmaceutical Science Institu
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Ishida Tatsuhiro
Department Of Pharmacokinetics And Biopharmaceutics Institute Of Health Biosciences The University O
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Kiwada H
Department of Pharmacokinetics and Biopharmaceutics, Faculty of Pharmaceutical Sciences, The University of Tokushima
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