Preparation And Blood Compatibility Evaluation Of Drug Eluting Stents

Vascular stents are widely used in intervention treatment, and stents implantation became a standard surgery of coronary angioplasty. However, In stent restenosis introduced by tissue hyperplasia and thrombosis is the major problem in clinic application. Recently, the technique of local drug delivery with a drug-eluting stent has been developed and considered a potential alternative to provide a solution. Several kinds of drug-loaded polymer coated stents were prepared, and blood compatibility was evaluated by four kinds of biological evaluation.Degradability of poly (lactic acid-co-glycol acid)(PLGA, 95,800dalton, 85:15; 60,000dalton, 75:25), poly (lactic acid) (PLA, 58,000dalton) and copolymer of poly(lactic acid)-glycol (PLEA, 100,000dalton, 90:10, PEG4000) was analyzed. Based on the results of weight loss, water absorption ratio, molecular weight change and platelet adherence, PLGA (95,800dalton, 85:15) was finally chosen as the carrier of drugs in this thesis. The optimized coating parameters are 0.03ml/min velocity of flow, 1.5W ultrasonic power, 1wt% solution weight concentration (ultrasonic degas for 10min before use), 30 circle times. Eleven kinds of stents were prepared with different drugs (curcumin, emodin, rapamycin and rapamycin/curcumin) and three kinds of concentration (10wt%, 20wt%, 30wt%). Pure PLGA coated stents and bared 316L stainless steel stents were prepared as comparison samples. Drug content of each drug-eluting stents was calculated. Scan electron microscope (SEM), atom force microscope (AFM) and motic digital optical microscope results showed that the surface of stents was very smooth and the coatings could withstand the compressive and tensile strains without cracking after the stent expansion process. Fourier transform infrared spectroscopy (FTIR) and X-ray electron spectroscopy (XPS) results indicated that there was no chemical reaction between drugs and PLGA. The high performance liquid chromatography (HPLC) was used to detect the release behavior of drugs. Curcumin-eluting stents and emodin-eluting stents showed approximately zero releasing dynamics and no burst release observed. 30wt% rapamycin-eluting stents had burst release in first two days, and then release smoothly. 10wt% and 20wt% rapamycin-eluting stents showed no obviously burst release. All rapamycin-eluting stents could release over two months. Platelet adherence experiment, activated partial thromboplastin time (APTT) test, GMP140 releasing test, fibrinogen adherence test were used to investigate the blood compatibility of drug eluting coatings. These results indicated that curcumin-loaded PLGA coated stents could reduce platelet activation and suppress endogenic clotting system. Emodin-loaded PLGA coated stents could reduce platelet adherence and activation but can not restrain endogenic clotting system, and so did rapamycin-loaded PLGA coated stents. Compared with rapamycin-eluting stents, rapamycin/curcumin-loaded PLGA coated stents had a better effect on inhibiting platelet adherence and activation, as well as extending APTT. However, the amount of adhered fibrinogen on the coating surface didn't show significantly difference. After all, curcumin could improve anticoagulant of rapamycin-eluting stents in a way.