Moriguchi Rumiko, Kogure Kentaro, Iwasa Akitada, Akita Hidetaka, Harashima Hideyoshi
Graduate School of Pharmaceutical Sciences, Hokkaido University, Kita 12 Nishi 6, Kita-ku, Sapporo, Hokkaido, Japan.
J Control Release. 2006 Feb 21;110(3):605-9. doi: 10.1016/j.jconrel.2005.10.021. Epub 2005 Dec 19.
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.
在非病毒基因递送系统（如脂质体/DNA复合物和八聚精氨酸修饰的多功能包膜型纳米装置（R8-MEND））的剂量与转染活性之间发现了显著的非线性关系。我们测量了不同剂量的R8-MEND转染后pDNA的核递送情况，以区分细胞内药代动力学或药效学中的非线性。当剂量增加时，在药效学中发现了显著的正非线性。即使是无意义的pDNA也能提高细胞核中每个pDNA的转录和/或翻译效率，但空脂质体则不能。这些结果表明，可控药效学以及细胞内药代动力学对于非病毒基因递送系统的合理设计具有重要意义。
