Pre-Study Of The Dexamethasone Drug-Eluting Stent

With the in-depth study of percutaneous coronary interventional treatment, the causes of in-stent restenosis and late complications have being revealed and understood. For the first-generation Drug-eluting stent (DEX), the long-term existence of non-biodegradable polymers in body can lead to persistent arterial wall inflammation and allergic reactions, which results in delayed vascular healing. The release rates of drug also gradually reduced with the decrease of the driving force, so there will still be a small amount of drug residues. The biodegradable polymers used for drug-carrier of DES have been developed, not only because their degradation products is carbon dioxide and water, which is safety, but also the drug in the stent can completely released with the degradation of coatings. These can be beneficial to re-endothelialization. In addition, restenosis after stent implantation is mainly identified by an inflammatory response to the procedural injury, an intense smooth muscle cell (SMC) proliferation and organized intraluminal thrombus formation. Modulation of this inflammatory response may potentially be a target to decrease neointimal hyperplasia and, subsequently, in-stent restenosis. A biodegradable polymer PLGA (poly(lactic-co-glycolic acid) was chosen as the carrier of dexamethasone (DEX), which was a kind of glucocorticoids. PLGA-DEX drug-eluting films were prepared with different drug content in this paper. In vitro cell compatibility, blood compatibility, drug release behavior and preparation course of dexamethasone drug-eluting stents were investigated.Four kinds of different PLGA-DEX films were prepared respectively with5%,15%,20%and30%drug content. The film composition, thickness and physical properties were characterized by Fourier transform-infrared spectroscopy (FT-IR), contact angle measurement and steps profiler. The FT-IR results indicated that the infrared spectra of PLGA-DEX film had the peaks of PLGA and dexamethasone simultaneously, which suggested that PLGA and dexamethasone existed in the PLGA-DEX film. The water contact angle were lower than that of PLGA, and with the drug content increasing, the hydrophilic nature of the PLGA-DEX film was improved. The thickness of PLGA-DEX film was depended on the DEX content, and the thicker film had the lower content of DEX. To evaluate the effect of dexamethasone on the cells, human smooth muscle cell (SMC) or endothelial cell (EC) were co-cultured with Dexamethasone in vitro. The results showed that the drug with10-7mol/L,10-8mol/L and10-9mol/L could significantly inhibit SMC proliferation, and the inhibition effect was concentration-dependent. As for the EC, only10-/mol/L drug played this role. In vitro adhesion and proliferation evaluation of SMC and EC on the PLGA-DEX films displayed that the PLGA-DEX films prohibited SMC and EC proliferation.Dexamethasone drug-eluting films could inhibit platelet adhesion and activation as well as suppress fibrinogen adsorption. This inhibiting effect had concentration-dependence. There were similar clotting times (APTT, PT, TT) for all PLGA-DEX films and plasma.The results of in vitro drug release behavior from dexamethasone-eluting films indicated that the dexamethasone existed burst release within lday, especially the5%DEX film and the15%DEX film. The5%DEX film released the drug completely in the first9days, and other three kinds of films had the stable release rate after6days. The higher of drug concentration was, the longer of drug release time was. Moreover, compared with the Rapamycin-eluting stent, it could be found that dexamethasone with samaller molecular weight was easily to be released.Finally, Dexamethasone-eluting stent were prepared using ultrasonic atomization spray method. The PLGA coating was smooth, uniform and intergrated. After stent expansion, there were still no cracks.