Non-linear pharmacodynamics in the transfection efficiency of a non-viral gene delivery system

International Journal of Pharmaceutics
Rumiko MoriguchiHideyoshi Harashima

Abstract

Transfection efficiencies using LipofectAMINE varied by more than three orders of magnitude depending on the concentrations of lipid and plasmid DNA (pDNA) used to prepare the lipoplexes. When lipoplexes were formed at lower concentrations a striking positive but non-linear relationship was found between dose and transfection efficiency, while at higher (i.e., normally used) concentrations a linear relationship was maintained. To determine the contribution of intracellular pharmacokinetics (PK) and pharmacodynamics (PD) to the observed nonlinearity, we quantified pDNA in whole cells and nuclei by real-time PCR and compared the results with the transfection efficiencies. There was no significant difference in the efficiency of intracellular PK; however, a remarkable difference was observed in the efficiency of PD. Analysis of individual cells by confocal laser scanning microscopy (CLSM) revealed that the amount of nuclear-delivered pDNA was higher for lipoplexes prepared at the normal concentration (NCL) compared to those of lipoplexes prepared at low concentration (LCL). Moreover, the size of the NCL was larger than that of the LCL. Both the size of the lipoplex particle and the dose appear to contribute to the non-linear effic...Continue Reading

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Citations

Apr 14, 2010·Pharmaceutical Research·Zinnia P Parra-GuillénIñaki F Trocóniz
Nov 6, 2013·Journal of Drug Targeting·Sorin Emilian Leucuta
May 30, 2012·Journal of Controlled Release : Official Journal of the Controlled Release Society·Yasuhiro HayashiHideyoshi Harashima
Oct 31, 2015·International Journal of Pharmaceutics·Amit Ranjan Maity, David Stepensky
Jan 27, 2015·IEEE Transactions on Nanobioscience·Timothy Michael MartinAngela K Pannier
Feb 22, 2012·Cellular Reprogramming·Sofia RibeiroJoaquim M Cabral
May 16, 2021·Advanced Materials·Zhen ZhangYouqing Shen
Feb 21, 2013·Molecular Pharmaceutics·Nathalie SymensKatrien Remaut

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