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可生物降解的聚(3-羟基丁酸酯)-聚(乙二醇)-聚(3-羟基丁酸酯)纳米颗粒作为潜在药物载体的体外细胞毒性、溶血试验及生物降解行为

In vitro cytotoxicity, hemolysis assay, and biodegradation behavior of biodegradable poly(3-hydroxybutyrate)-poly(ethylene glycol)-poly(3-hydroxybutyrate) nanoparticles as potential drug carriers.

作者信息

Chen Cheng, Cheng Yin Chung, Yu Chung Him, Chan Shun Wan, Cheung Man Ken, Yu Peter H F

机构信息

State Key Laboratory of Chinese Medicine and Molecular Pharmacology, Department of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University, Hong Kong, People's Republic of China.

出版信息

J Biomed Mater Res A. 2008 Nov;87(2):290-8. doi: 10.1002/jbm.a.31719.

Abstract

Nanoparticles based on amorphous poly(3-hydroxybutyrate)-poly(ethylene glycol)-poly(3-hydroxybutyrate) (PHB-PEG-PHB) are potential drug delivery vehicles, and so their cytotoxicity and hemolysis assay were investigated in vitro using two kinds of animal cells. The PHB-PEG-PHB nanoparticles showed excellent biocompatibility and had no cytotoxicity on animal cells, even when the concentrations of the PHB-PEG-PHB nanoparticle dispersions were increased to 120 microg/mL. Moreover, no hemolysis was detected with the PHB-PEG-PHB nanoparticles, suggesting that the PHB-PEG-PHB nanoparticles were obviously much hemocompatible for drug delivery applications. In the presence of intracellular enzyme esterase, the biocompatible PHB-PEG-PHB nanoparticles might be hydrolyzed, and their biodegradable behavior was monitored by the fluorescence spectrum and the pH meter. The initial biodegradation rate of the PHB-PEG-PHB nanoparticles was closely related to the enzymatic amount and the PHB block length. Compared with that obtained from the fluorescence determination, the initial biodegradation rate from pH measurement was faster. The biodegraded products mainly consisted of 3HB monomer and dimer, which were the metabolites present in the body.

摘要

基于无定形聚(3-羟基丁酸酯)-聚(乙二醇)-聚(3-羟基丁酸酯)(PHB-PEG-PHB)的纳米颗粒是潜在的药物递送载体,因此使用两种动物细胞在体外研究了它们的细胞毒性和溶血试验。PHB-PEG-PHB纳米颗粒表现出优异的生物相容性,即使将PHB-PEG-PHB纳米颗粒分散体的浓度增加到120μg/mL,对动物细胞也没有细胞毒性。此外,未检测到PHB-PEG-PHB纳米颗粒的溶血现象,这表明PHB-PEG-PHB纳米颗粒在药物递送应用中具有明显更好的血液相容性。在细胞内酶酯酶存在的情况下,生物相容性的PHB-PEG-PHB纳米颗粒可能会被水解,并通过荧光光谱和pH计监测其生物降解行为。PHB-PEG-PHB纳米颗粒的初始生物降解速率与酶量和PHB嵌段长度密切相关。与荧光测定得到的结果相比,pH测量得到的初始生物降解速率更快。生物降解产物主要由3HB单体和二聚体组成,它们是体内存在的代谢产物。

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