Non-linear pharmacodynamics in a non-viral gene delivery system: positive non-linear relationship between dose and transfection efficiency.
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.
Moriguchi
Rumiko
R
Graduate School of Pharmaceutical Sciences, Hokkaido University, Kita 12 Nishi 6, Kita-ku, Sapporo, Hokkaido, Japan.
Kogure
Kentaro
K
Iwasa
Akitada
A
Akita
Hidetaka
H
Harashima
Hideyoshi
H
D000818:Animals; D004247:DNA / Q000008:administration & dosage / Q000235:genetics* / Q000493:pharmacokinetics*; D018014:Gene Transfer Techniques; D007425:Intracellular Membranes / Q000187:drug effects / Q000502:physiology; D051379:Mice; D041681:NIH 3T3 Cells; D017711:Nonlinear Dynamics; D014162:Transfection / Q000379:methods*
D004247:DNA