Preparation And Inveatigation Of Multi-Functional Coating Of Gallic Acid

Atherosclerosis disease (coronary heart disease) is one of the common disease which threatened the health and life of human people severely, becoming the leading cause of premature death globally. The drug-eluting stent (DES) is the most common means for the treatment of severe coronary heart disease in the clinic which greatly reduces the restenosis to a rate of less than10%. However the DES has some drawbacks, these are long-term endothelial dysfunction, non selective cytotoxicity and late stent thrombosis. Currently the drug-eluting coatings of Cypher and Taxus are mainly available in the clinic which is principally focused on inhibiting vascular smooth muscle cell (VSMC) proliferation. However the growth of endothelial cells (EC) is also suppressed by these drugs at the same time, resulting in a delayed regeneration of endothelium as well as the above problems. Although the pathobiology of atherosclerosis is a complex multifactorial process, the regulation of platelet, endothelial and smooth muscle cell fate are considered to be the most important function of an ideal vascular stents or graft for atherosclerosis treatment. Hence, it is significantly important to find a drug or molecule with selective cytotoxicity between VSMC and EC, which strongly inhibits the growth of VSMC, while promotes the growth of EC or has lesser cytotoxicity for EC compared with VSMC at least, and balances anticoagulation function. In this work, gallic acid which is a natural polyphenol was chosen as the drug for drug-eluting stent. The effect of gradient concentration of gallic acid on endothelial and smooth muscle cells was investigated through alone-culture and co-culture methods. It was demonstrated that gallic acid promoted the growth of human umbilical vein endothelial cells (HUVECs) and suppressed the proliferation of human umbilical artery smooth muscle cells (HUASMCs) at the concentration of5mg/ml. Then, gallic acid was mixed into poly(1,3-trimethylene carbonate) to prepare GA-loaded PTMC film via solvent evaporation. And material characteristics and biological evaluations are carried out by different means. These results showed that the GA-loaded PTMC film inhibited the adhesion and activation of platelets, indicating a good anticoagulant performance. Also, this film with a certain GA loading (1wt%) provided significant enhancement for the adhesion and proliferation of HUVECs and inhibition of the growth of HUASMCs. The drug release behavior of gallic acid from GA-PTMC film indicated that gallic acid enriched on the surface of the film. Finally, GA-PTMC film was prepared on stent using ultrasonic atomization spray method. However, the drug release behavior and the process of spraying on the stent of GA-PTMC film needed further improvement, these data suggested the large potential of GA for drug-eluting stent and other vascular devices.