Non-linear pharmacodynamics in a non-viral gene delivery system: Positive non-linear relationship between dose and transfection efficiency
Non-linear pharmacodynamics in a non-viral gene delivery system: Positive non-linear relationship between dose and transfection efficiency
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DOI：
10.1016/j.jconrel.2005.10.021
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发表时间：
2006-02-21
影响因子：
10.8
通讯作者：
Harashima, H
中科院分区：
文献类型：
--
作者：
Moriguchi, R;Kogure, K;Harashima, H
非病毒基因传递系统（如脂质体/DNA复合物和八精氨酸修饰的多功能包膜型纳米装置（R8-MEND））的转染活性与剂量之间存在显著的非线性关系。我们测量了pDNA的核传递，以区分不同剂量R8-MEND转染后细胞内药代动力学或药理学的非线性。随着剂量的增加，药效学呈显著的正非线性。即使是假的pDNA也能提高细胞核中每个pDNA的转录和/或翻译效率，但空脂质体却没有。这些结果表明控制药效学的重要性以及细胞内药代动力学对合理设计非病毒基因传递系统的重要性。(C) 2005 Elsevier B.V.版权所有
A remarkable non-linearity was found between dose and transfection activities of non-viral gene delivery systems, such as a Lipofectamine/DNA complex and an octaarginine-modified multifunctional envelope-type nano device (R8-MEND). We measured the nuclear delivery of pDNA to distinguish the non-linearity in intracellular pharmacokinetics or pharmacodynamics after transfection with R8-MEND at different doses. A remarkable positive non-linearity was found in the pharmacodynamics when the dose was increased. Even dummy pDNA enhanced the efficiency of transcription and/or translation per pDNA in the nucleus, but empty liposomes did not. These results suggest the importance of controlled pharmacodynamics as well as the importance of intracellular pharmacokinetics for the rational design of non-viral gene delivery systems. (C) 2005 Elsevier B.V. All rights reserved.