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Non-linear pharmacokinetics of octaarginine-modified lipid nanoparticles: Barriers from in vitro to in vivo

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Title: Non-linear pharmacokinetics of octaarginine-modified lipid nanoparticles: Barriers from in vitro to in vivo
Authors: Hayashi, Yasuhiro Browse this author →KAKEN DB
Noguchi, Yuki Browse this author
Harashima, Hideyoshi Browse this author →KAKEN DB
Keywords: Octaarginine
In vitro and in vivo
Issue Date: 10-Aug-2012
Publisher: Elsevier B.V.
Journal Title: Journal of Controlled Release
Volume: 161
Issue: 3
Start Page: 757
End Page: 762
Publisher DOI: 10.1016/j.jconrel.2012.05.036
PMID: 22641061
Abstract: A rational development of an efficient siRNA delivery system is important for streamlining the RNAi-based drug development process. However, a huge gap frequently exists between in vitro and in vivo activity, which is the rate limiting step for developing versatile nanoparticles. We report herein on a remarkable non-linearity in pharmacokinetics (PK), but not the pharmacodynamics (PD) using octaarginine (R8) modified lipid nanoparticles in mice. A quantitative study of siRNA molecules between cultured cells and mouse liver revealed a high correlation between intracellular siRNA molecules and their RNAi activities, indicating that there was no significant difference in the efficiency in PD. In contrast, a remarkable difference was observed in the non-linearity in PK. Quantitative analysis of the time profile for siRNA showed that the percentage of siRNA accumulation in mice was severely decreased with decreasing input dose compared to in vitro data. These unexpected data reveal an important clue to bridging the gap between in vitro and in vivo activity.
Type: article (author version)
Appears in Collections:薬学研究院 (Faculty of Pharmaceutical Sciences) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

Submitter: 林 泰弘

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