Construction Of Cardiovascular Genes, Drug Nano Delivery Systems And Their Use In The Treatment Of Vascular Restenosis

Cardiovascular disease is the leading cause of death.Currently,interventional procedures,including balloon angioplasty,percutaneous transluminal coronary angioplasty(PTCA)and stent implantation are some routinely employed therapeutic options for cardiovascular diseases,although patients often develop restenosis following these procedures.We had prepared a stent that co-elutes VEGF plasmid and PTX packaged,one month after implantation in the coronary artery of pigs,the NPs-eluting stent resulted in complete re-endothelialization and restenosis inhibition.However,30-40%of critical vascular lesions,such as lesions in branch sites or small arteries that cannot be surgically operated with vascular stent.Therefore,we explored an approach to local administration of biayered-NPs by a perfusion balloon to the intra-vascular site.In addition,aiming at how to efficiently improve drug delivery in the vascular lesion,we used convenient and simple synthetic method to synthesize the amphiphilic polymer 3S-PLGA-PEG.Series of researches were performed to access properties of the carrier material.The first part:We designed bilayered-NPs,which contained the VEGF plasmid in the shell and PTX within the core,bilayered-NPs released gene and drug sequentially.In this study,we characterized the properties of the bilayered-NPs and evaluated the efficacy of bilayered-NPs in vivo.Rabbits treated with the bilayered NPs exhibited rapid re-endothelialization and inhibition of restenosis.These results had demonstrated that bilayered-NPs experted a beneficial effect on reducing atherosclerotic restenosis through local perfusion.The second part:In this study,we first used the oxalyl chloride as the linker to synthesize the three-arm poly(lactic-co-glycolic acid)-poly(ethylene glycol)(3S-PLGA-PEG),and compared with literature-reported,this method shortened the reaction procedure and improved the reaction yield.The results of fourier-transform infrared(FTIR),gel permeation chromatography(GPC)and hydrogen nuclear magnetic resonance spectrum(1H NMR)suggested that 3S-PLGA-PEG was successfully synthesized.The characterization of RPM-loaded micelle indicated that the 3S-PLGA-PEG was suitable for drug carrier application.Therefore,the use of oxalyl chloride was a novel and simple method to synthesize the amphiphilic copolymer as drug carrier.