Effective uptake of N-acetylglucosamine-conjugated liposomes by cardiomyocytes in vitro.
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-1beta (IL-1beta)-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-1beta-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.
Division of Cardiovascular Sciences, Department of Organ Regeneration, Shinshu University Graduate School of Medicine, Asahi, Matsumoto, Nagano, Japan.
Shin-ichi
S
Aso
Hirohiko
H
Ise
Masafumi
M
Takahashi
Satoshi
S
Kobayashi
Hajime
H
Morimoto
Atsushi
A
Izawa
Mitsuaki
M
Goto
Uichi
U
Ikeda
D000117:Acetylglucosamine / Q000737:chemistry*; D000818:Animals; D000831:Animals, Newborn; D002478:Cells, Cultured; D002626:Chemistry, Pharmaceutical; D004339:Drug Compounding; D004705:Endocytosis; D004790:Enzyme Induction; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D053583:Interleukin-1beta / Q000378:metabolism; D008055:Lipids / Q000737:chemistry*; D008081:Liposomes; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000096:biosynthesis; D010316:Particle Size; D017035:Pravastatin / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley
D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D053583:Interleukin-1beta; D008055:Lipids; D008081:Liposomes; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; D017035:Pravastatin; D000117:Acetylglucosamine