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

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)189-198
Number of pages10
JournalJournal of Controlled Release
Volume122
Issue number2
DOIs
Publication statusPublished - Sep 26 2007
Externally publishedYes

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Acetylglucosamine
Cardiac Myocytes
Liposomes
Pravastatin
Drug Delivery Systems
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Nitric Oxide Synthase Type II
Interleukin-1
Myocardium
Nitric Oxide
Hydroxymethylglutaryl CoA Reductases
In Vitro Techniques
Glycosides
Heart Diseases
Flow Cytometry
Fluorescence

All Science Journal Classification (ASJC) codes

  • Pharmaceutical Science

Cite this

Effective uptake of N-acetylglucosamine-conjugated liposomes by cardiomyocytes in vitro. / Aso, Shin ichi; Ise, Hirohiko; Takahashi, Masafumi; Kobayashi, Satoshi; Morimoto, Hajime; Izawa, Atsushi; Goto, Mitsuaki; Ikeda, Uichi.

In: Journal of Controlled Release, Vol. 122, No. 2, 26.09.2007, p. 189-198.

Research output: Contribution to journalArticle

Aso, SI, Ise, H, Takahashi, M, Kobayashi, S, Morimoto, H, Izawa, A, Goto, M & Ikeda, U 2007, 'Effective uptake of N-acetylglucosamine-conjugated liposomes by cardiomyocytes in vitro', Journal of Controlled Release, vol. 122, no. 2, pp. 189-198. https://doi.org/10.1016/j.jconrel.2007.07.003
Aso, Shin ichi ; Ise, Hirohiko ; Takahashi, Masafumi ; Kobayashi, Satoshi ; Morimoto, Hajime ; Izawa, Atsushi ; Goto, Mitsuaki ; Ikeda, Uichi. / Effective uptake of N-acetylglucosamine-conjugated liposomes by cardiomyocytes in vitro. In: Journal of Controlled Release. 2007 ; Vol. 122, No. 2. pp. 189-198.
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