Nanoscaled Polyion Complex Micelles for Targeted Delivery of Recombinant Hirudin to Platelets Based on Cationic Copolymer

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• 作者：Fei Wang ; Xinru Li ; Yanxia Zhou ; Yanhui Zhang ; Xingwei Chen ; Jingxiong Yang ; Yanqing Huang ; Yan Liu
• 刊名：Molecular Pharmaceutics
• 出版年：2010
• 出版时间：June 7, 2010
• 年：2010
• 卷：7
• 期：3
• 页码：718-726
• 全文大小：239K
• 年卷期：v.7,no.3(June 7, 2010)
• ISSN：1543-8392

文摘

Polyion complex (PIC) micelles based on methoxy poly(ethylene glycol)-grafted-chitosan (mPEG-g-chitosan) and Arg-Gly-Asp conjugated poly(ethylene glycol)-grafted-chitosan (RGD−PEG-g-chitosan) were designed as carriers for platelet-targeted delivery of recombinant hirudin variant-2 (rHV2). The rHV2-loaded plain PIC micelles (mPIC micelles) and RGD conjugated PIC micelles (RGD−PIC micelles) were successfully prepared with mean size of 30.9 ± 0.5 nm and 41.9 ± 1.8 nm, and their encapsulation efficiencies were 76.90 ± 0.84% and 81.08 ± 0.85%, respectively. The pharmacokinetics experiments showed that the mean retention time (MRT) of rHV2 encapsulated in both kinds of micelles was significantly prolonged, especially for mPIC micelles. The confocal laser scanning microscopy intuitively proved the specific binding of RGD−PIC micelles to platelets. The efficacies of rHV2-loaded RGD−PIC micelles were greatly better than those of rHV2-loaded mPIC micelles and rHV2 solution in aspect of anticoagulation and inhibition of platelet aggregation. These results suggested platelet-targeting specificity of RGD−PIC micelles and that RGD−PIC micelles could potentially be used as a carrier for platelet-targeted delivery and long circulation of rHV2.