The Research On Drug-Eluting Stents

Currently, restenosis after percutaneous transluminal coronary angioplasty (PTCA) and stent implantation is the major difficult problem of the field of cardiovascular intervention therapy in the world. The anticoagulation of clinical rapamycin and paclitaxel eluting stents is still deficient; furthermore, the long-standing nonbiodegradable polymer drug carrier in human body may also bring many clinical complications because of the change of its structure and properties. To above questions, this study aimed at developing a novel drug-eluting stent with a biodegradable polymer coating which contained not only antiproliferative drug but anticoagulation drug. Considering the good anticoagulation and anti-proliferation of some Chinese herbal drug, this paper carried out some exploring studies of these drugs eluting stentsAccording to the controlled release requirements, biodegradable behavior and the clinical admittance of biodegradable biomaterials, the PLGA (poly lactide-co-glycoide) (Its average-viscosity molecular weight was 95800, LA/GA=85/15) was chosen as the drug carrier in this paper. Anti-proliferative drug including rapamycin and paclitaxel, anticoagulation drug such as heparin and Chinese herbal drug including curcumin and emodin were investigated. Five single drug-eluting stents (rapamycin, paclitaxel, curcumin, emodin and heparin) and three mixing-drug eluting stents (rapamycin-heparin, curcumin-heparin and rapamycin-curcumin) were prepared using ultrasonic atomization spray method.The comparative results of pre- and post-dilation morphology of drug eluting stents indicated that the coating was very smooth, uniform and integrated. There were no webbings and "bridges" between struts. The avergae roughness of coating measured by atomic force microscopy (AFM) was below 1nm. The drug-eluting stents were mounted onto a angioplasty balloon (3.0×20mm) and then dilated, the coating did not peel and crack, suggesting that the coating had the ability to withstand the compressive and tensile strains imparted during this process. The results of Fourier transform infrared spectroscopy (FTIR) and X-ray photoelectron spectroscopy (XPS) indicated that there was no peak shift for drug in drug-eluting PLGA films. The results of in vitro drug release profile from stents indicated that different drug had different release behavior. The release profile of curcumin and emodin from stents exhibited approximate zero-order release profile, however, the release rate of curcumin was larger than emodin, for example, the curcumin-eluting stent which contained 20wt% curcumin was 7.37μg/day and that of emodin was 4.9μg/day, the different release rate resulted in different release period. The release behavior of rapamycin from stent had a two phase release profile with a burst release within 2 days, the burst release changed from 4.7% to 20% with the increase of drug content from 15% to 40%, after initial burst release (2 days) followed by a longer lasting, slower sustained release, the decreased release phase appeared to a approximate zero-order release model. The heparin release from heparin-eluting stents had an approximate zero-order release profile without burst release and the heparin release of rapamycin-heparin and curcumin-heparin eluting stents exhibited good zero-order profile, however, the release behavior of rapamycin and curcumin was similar with corresponding single drug-eluting stents and the release rate was different. The drug content influenced the release rate significantly and the release rate increased with the increase of drug content but was not proportional to ratio of drug-polymer. The control release layer prepared from PLGA20000 onto single rapamycin-eluting stent surface can eliminate the burst release of rapamycin and prolong the release period of rapamycin.In this study, platelet adhesion and activation (GMP140, P-selection), activated partial thromboplastin time (APTT) and fibrinogen adsorption were used to characterize the blood compatibility of drug-eluting stent. Compared with stainless steel and single PLGA coating stent, the heparin and curcumin eluting stents had a good hemocompatibility, however, the blood compatibility of rapamycin-eluting stent was deficient. Incorporating curcumin in rapamycin-eluting stents can improve the anticoagulation of rapamycin-eluting stent. Loading heparin in curcumin-eluting stent further enhanced the anticoagulation of curcumin-eluting stent. This established good base for developing drug-eluting stents which had not only good anticoagulation but also anti-proliferation.The biological evaluation results of LDH, Alamar Blue^TM and cell staining indicated that three kinds of drug-loaded films, including rapamycin, curcumin, heparin loading PLGA films, all can inhibit smooth muscle cell grow and proliferate compared with stainless steel and PLGA. The order of effect was rapamycin＞curcumin＞heparin. The anti-proliferation effect improved with the increase of drug content.