Effective uptake of N-acetylglucosamine-conjugated liposomes by cardiomyocytes in vitro
Effective uptake of N-acetylglucosamine-conjugated liposomes by cardiomyocytes in vitro
复制标题
DOI：
10.1016/j.jconrel.2007.07.003
复制
发表时间：
2007-09-26
影响因子：
10.8
通讯作者：
Ikeda, Uichi
中科院分区：
文献类型：
--
作者：
Aso, Shin-ichi;Ise, Hirohiko;Ikeda, Uichi
靶向损伤心肌的给药系统（DDS）将成为一种新的心脏疾病治疗工具。为了开发这样的DDS，我们研究了两种含荧光底物的糖苷偶联脂质体与心肌细胞的相互作用。流式细胞术显示心肌细胞与n -乙酰氨基葡萄糖偶联脂质体（GlcNAc-Ls）充分相互作用。此外，为了证实包裹在GlcNAc-Ls中的药物是否会影响心肌细胞的细胞内环境，我们制备了含有普伐他汀的GlcNAc-Ls，并检测了普伐他汀对心肌细胞的影响。普伐他汀是一种3-羟基-3-甲基戊二酰辅酶a还原酶抑制剂（他汀类药物），具有亲水性。据报道，亲脂性他汀类药物可通过白细胞介素-1 β (IL-1 β)刺激心肌细胞促进一氧化氮（NO）的产生和诱导型一氧化氮合酶（iNOS）的表达。普伐他汀的亲水性阻止其进入心肌细胞；因此，它不能同时增强这两个过程。含glcnac - ls的普伐他汀治疗可特异性增强IL-1 β刺激的心肌细胞NO生成和iNOS表达。基于这些结果，我们发现心肌细胞与GlcNAc-Ls表现出高度的相互作用，并且GlcNAc-Ls包膜的药物可以被心肌细胞有效吸收。我们认为glcnac - l可以作为损伤心肌的DDS进行治疗。(C) 2007 Elsevier B.V.版权所有
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 interieukin-1 beta (IL-1 beta)-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-1 beta-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. (C) 2007 Elsevier B.V. All rights reserved.