Preparation And Characterization Of Double Sided Drug Coating Stent

Percutaneous transluminal angioplasty was a revolutionary change in the field of vascular disease treatment. In 1986, Sigwart et al implanted intravascular stents in coronary artery for the first time, which opened a new era in the treatment of vascular stenosis disease. However, through the clinical observation, it found that the in-stent restenosis rate is as high as 20% ~ 30% in patients who received the bare metal stents implantation, the restenosis rate reached the peak between 3 to 6 months and reduced after 6 months. While drug coating stent implanted into the lesion site, drugs released slowly from polymer to the local damage site to play sustainable and efficient biological effects and reduce the restenosis rate to below 10%. The drug coating stent lead to new problems, such as endothelialization delaye, late and very late in-stent thrombosis. Thus, the design of new drug-eluting stent to solve the problems becomes a hot topic in the fieldThe issues in the preparation process of DES were generally focused on three chief aspects, including the selection of drug, drug carrier, and preparation technology. In this article the chitosan(CS) loaded platelet membrane glycoprotein IIIa monoclonal antibody(SZ-21) as stent luminal layer, and poly lactic acid glycolic acid copolymer(PLGA) loaded docetaxel(DTX) as stent outer layer. The asymmetric double sided drug coating stent is prepared by ultrasonic atomization. After testing the characteristics of the double sided drug coating stents in vitro, we examined intimal hyperplasia and thrombosis by implanted the asymmetric double sided drug coating stents into rabbit carotid artery. The major contents and results of the research were as follows.(1)The ultrasonic atomization for experiment was advanced and prepared for the double sided drug coating stent. We improved the ultrasonic atomization device and chose the coating parameters. The optimized CS and SZ-21 coating parameters focused on three aspects, the processing project number was 15, the rotational and the forward speed of the stent was 2r/s and 1 r/s, respectively. The processing project number of PLGA and DTX coating was 8, and the rotational and forward speed of the stent was 3 r/s and 1 r/s, respectively.(2)The prepared double sided drug coating stents were characterized by scanning electron microscope, the results showed that the drug coating was uniform Ly distributed and without aggregation phenomenon. Then the element analysis proved the coating was completely covered. There was non-shedding phenomenon appeared before and after stent expansion. We have found the drug on the double sided drug coating stents was asymmetric distribution through fluorescence label. The release results of double sided drug coating showed that SZ-21 cumulative release rate was 40.11%, while the DTX cumulative release rate was 27.22% within the first 24 hours. From 7 days to 28 days, the SZ-21 and DTX cumulative release rate were 64.27% and 53.23%, respectively, and the content of SZ-21 and DTX remaining 35.73% and 46.77% until 28 d.(3) We have tested the blood compatibility of the double sided drug coating stent and the effect on the proliferation of vascular smooth muscle cells in vitro. Hemolysis rate of the double sided drug coating stent was lower than 5 %, which meets the national standards. The double sided drug coating stent with SZ-21 could prolonged the time of APTT, PT, TT, and reduce fibrinogen adsorption and platelet adhesion. After vascular smooth muscle cells co-cultured with double sided drug coating stent 1, 3 and 5 days, the double sided drug coating stent containing DTX can significantly inhibit vascular smooth muscle cell proliferation, through MTS proliferation assay and immunofluorescence staining.(4) We implanted the 316 L stainless steel stent and double sided drug coating stent into rabbit carotid artery to study the thrombosis prevention and cure ISR by scanning electron microscopy observation and tissue staining. The blood vessel, serum samples and main organs and tissues were got from the rabbits after stents implantation for 4 weeks and 12 weeks. The results showed that the double sided drug coating stent was safe and could effectively prevent thrombosis and in-stent restenosis in the 3-month observation period.