Study On Poly (1, 3-Trimethylene Carbonate) Blend With Poly (Ethene Glycol) Applied In Drug-Eluting Stent Coating

The drug-eluting stents (DES) has created a revolution in practice of interventional cardiology. A lot of studies have been taken to improve the defects of the first generation drug-eluting stents. The development of drug-eluting stent coatings and selection of new drugs are major improvement directions of DES. The biodegradable polyesters such as poly (lactic acid) (PLA) and poly (lactic-co-glycolic acid) (PLGA) have been used as drug eluting coating. However, these biodegradable polymers still have certain limitations in application because of bulk erosion. It is well known that these polymers are bulk erosion and the polymers will become loose, hard and brittle during the degradation process. Furthermore, the bulk erosion polymers present large area shedding and their mechanical strengths decrease quickly during the degradation process. In addition, the bulk erosion polyester also induces internal autocatalysis and causes fast release of acidic degradation products in the degradation stage, and finally causes unfavorable effects. It has been confirmed in our previous research that some properties of poly (1,3-trimethylene carbonate) (PTMC) such as good biocompatibility, strong mechanically, the degradation mechanism of surface erosion and no acidic degradation products are suitable for DES coating. However, the hydrophobic nature of PTMC is disadvantageous in these blood-contacting materials.In this paper, three kinds of different molecular weight (10000,4000, and 1000) PEG were respectively blended with PTMC, and three kinds of composite films (P-P10, P-P4 and P-P1 PTMC:PEG=70%:30%) were prepared respectively. The results of Fourier Transform infrared spectroscopy (FTIR), X-ray diffraction (XRD) and differential scanning calorimetry (DSC) indicated that the blending of PTMC and PEG was the physical blending. In the process of forming the films, the PTMC and PEG influenced each other and reduced the crystallization properties respectively. The measurement of contact angle was adopted to evaluate the hydrophilicity and surface energy of the blended films. As blended with PEG, the hydrophilicity of PTMC was significantly improved and the surface energy of blended films was enhanced. The molecular weight of the PEG was smaller, the hydrophilicity of PTMC/PEG film was better and the surface energy of PTMC/PEG film was higher. In vitro degradation behavior of the PTMC/PEG films in phosphate buffered saline were studied by gel permeation chromatography (GPC), weighting method and scanning electron microscope(SEM). The results showed that the solution of PEG were the main degradation mode within 4 weeks, and the dissolving rate increased with the decrease of PEG molecular weight. The molecular weight of PTMC kept stable in 30 days for all blended films.In vitro hemocompatibility evaluation revealed that there were lower platelet adhesion, platelet activation and fibrinogen activation on the PTMC/PEG films compared with the PTMC film. PTMC/PEG4000 and PTMC/PEG 1000 had the better hemocomatibility. In vitro evaluation of cell adhesion and proliferation showed there were good endothelial cells and smooth muscle cells adhesion and proliferation on the surface of PTMC/PEG films.In vitro drug release profile of PTMC/PEG4000 film loaded by tacrolimus(coded as P-P4Ta) indicated that tacrolimus existed burst release within 3 day and then the releasing rate kept stable. Because the solution of the PEG increased the release of tacrolimus, the burst release of P-P4Ta was remarkable than that of PTMC-Ta, and the releasing rate and the releasing amount were also larger than those of PTMC-Ta. The P-P4Ta film had the anticoagulation and could inhibit smooth muscle cells proliferation.