论文摘要
To achieve targeted thrombolysis, a targeted delivery system of lumbrokinase（LK） was constructed using RGDfk-conjugated hybrid micelles. Based on the specific affinity of RGDfk to glycoprotein complex of GP Ⅱ b/Ⅲ a expressed on the surface of membrane of activated platelet, LK loaded targeted micelles（LKTM） can be delivered to thrombus. The hybrid micelles were composed of polycaprolactone-block-poly（2-（dimethylamino） ethyl methacrylate）（PCL-PDMAEMA）, methoxy polyethylene glycol-block-polycaprolactone（mPEG-PCL）and RGDfk conjugated polycaprolactone-block-polyethylene glycol（PCL-PEG-RGDfk）. PCLPDMAEMA was synthesized via ring open polymerization（ROP） and atom transfer radical polymerization（ATRP）. PCL-PEG-RGDfk was synthesized via ROP and carbodiimide chemistry. The prepared LKTM was characterized by dynamic light scattering（DLS） and transmission electron microscope（TEM）. Colloidal stability assay showed the prepared LKTM was stable. Biocompatibility assay was performed to determine the safe concentration range of polymer. The assay of fluorescent distribution in vivo demonstrated that LKTM can be efficiently delivered to thrombi in vivo. Thrombolysis in vivo indicated the thrombolytic potency of LKTM was optimal in all groups. Notably, the laboratory mice treated with LKTM exhibited a significantly shorter tail bleeding time compared to those treated with LK or LK-loaded micelles without RGDfk, which suggested that the targeted delivery of LK using RGDfk-conjugated hybrid micelles effectively reduced the bleeding risk.
论文目录
文章来源
类型: 期刊论文
作者: Yang Pan,Xiahui Wang,Zongning Yin
来源: Asian Journal of Pharmaceutical Sciences 2019年02期
年度: 2019
分类: 医药卫生科技,工程科技Ⅰ辑
专业: 有机化工,药学
单位: Key Laboratory of Drug Targeting and Drug Delivery Systems, West China School of Pharmacy, Sichuan University
基金: financially supported by National Natural Science Foundation of China(No.81673363)
分类号: R943
页码: 144-153
总页数: 10
文件大小: 716K
下载量: 8
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