REDV/雷帕霉素复合涂层构建内皮细胞选择性功能界面

REDV/Peptide Conjugated Rapamycin-loaded Polymer Matrix for Endothelial Cells Selectivity

运用复合涂层的概念构建了兼具药物洗脱和内皮促进作用的载药涂层.以载雷帕霉素(Rapamycin,RAP)的聚乙二醇甲基丙烯酸酯(PEGMA)-甲基丙烯酸丁酯(BMA)(PEGMA-BMA,PEGB)为内层,Arg-Glu-Asp-Val(REDV)多肽修饰的PEGBN[PEGBA-BMA-对硝基苯氧羰基聚乙二醇甲基丙烯酸酯(MEONP)]为外层包裹载药涂层.体外药物释放结果表明,雷帕霉素可以维持缓慢稳定的长效释放,释放过程中没有出现暴释现象.表面细胞生长行为表明,雷帕霉素可以有效地阻抗内皮细胞和平滑肌细胞的黏附,抑制细胞活性;随着药物释放的进行,雷帕霉素浓度逐渐减低,但涂层依然维持对平滑肌细胞的非特异性阻抗;而REDV修饰的外涂层开始呈现内皮细胞的选择性黏附,随着释放时间延长,内皮细胞特异选择性也逐渐加强.雷帕霉素和REDV多肽协同构建的复合涂层能够有效抑制平滑肌细胞的增殖,获得内皮细胞选择性黏附.

Combination device containing drug release and HUVECs selectivity were constructed based on PEG copolymer.Polyethylene glycol methacrylate（PEGMA）-butyl methacrylate（BMA）（PEGB） loading rapamycin was cast onto polyethylene terephthalate（PET） substrate as base layer,and then PEGMA-BMA-p-nitrophenyloxycarbonyl polyethylene glycol methacrylate（MEONP）（PEGBN） conjugated REDV peptide was further coated as top layer.In vitro profile of drug release indicates that rapamycin keeps a slow and sustain release implying that the top layer acts as a diffusion barrier.Cell behavior indicates that rapamycin remains its activity in inhibiting human umbilical vein endothelial cells（HUVECs） and human aortic smooth muscle cells（HASMCs） adhesion and proliferation.Although the eluted concentration of rapamycin decreased with drug eluting time,the polymeric coating keeps resisting nonspecific adsorption of HASMCs while REDV enhances HUVECs attachment specifically.This polymeric film with top layer promotes HUVECs competitive adhesion comparing with HASMCs.The immobilization of REDV onto rapamycin loaded PEG matrix could be an effective method to keep sustained inhibition of HASMCs and promote HUVECs competitive adhesion simultaneously.