Effective uptake of N-acetylglucosamine-conjugated liposomes by cardiomyocytes in vitro

Shin ichi Aso, Hirohiko Ise, Masafumi Takahashi, Satoshi Kobayashi, Hajime Morimoto, Atsushi Izawa, Mitsuaki Goto, Uichi Ikeda

研究成果: Contribution to journalArticle査読

28 被引用数 (Scopus)

抄録

A drug delivery system (DDS) that targets the injured myocardium would serve as a novel therapeutic tool for cardiac diseases. To develop such a DDS, we investigated the interaction of 2 types of glycoside-conjugated liposomes containing a fluorescence substrate with cardiomyocytes. Flow cytometry revealed that cardiomyocytes adequately interact with N-acetylglucosamine-conjugated liposomes (GlcNAc-Ls). Furthermore, to confirm whether the agents encapsulated in GlcNAc-Ls affect the intracellular environment of cardiomyocytes, we prepared GlcNAc-Ls-containing pravastatin and examined the effect of pravastatin on cardiomyocytes. Pravastatin is a 3-hydroxy-3-methylglutaryl-CoA reductase inhibitor (statin) and is hydrophilic. It is reported that lipophilic statins enhance nitric oxide (NO) production and inducible nitric oxide synthase (iNOS) expression by interleukin-1β (IL-1β)-stimulated cardiomyocytes. The hydrophilic nature of pravastatin prevents its entry into cardiomyocytes; therefore, it cannot enhance both these processes. Treatment with GlcNAc-Ls-containing pravastatin specifically enhanced NO production and iNOS expression by IL-1β-stimulated cardiomyocytes. Based on these results, we found that cardiomyocytes exhibit a high degree of interaction with GlcNAc-Ls, and GlcNAc-Ls-encapsulated agents can be effectively taken up by cardiomyocytes. We suggest that GlcNAc-Ls can be utilized therapeutically as a DDS for the injured myocardium.

本文言語英語
ページ(範囲)189-198
ページ数10
ジャーナルJournal of Controlled Release
122
2
DOI
出版ステータス出版済み - 9 26 2007
外部発表はい

All Science Journal Classification (ASJC) codes

  • 薬科学

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