Application Of Proteins On Drug-Eluting Stent

Drug-eluting stents have widely been accepted and applied in clinical treatment of atherosclerotic stenosis for its effectiveness in reducing incidence of restenosis after percutaneous coronary intervention. However, the chemical ingredients loaded on the drug-eluting stents currently used in clinics are less selective, thus they do not only suppress the proliferation of smooth muscle cell but aslo inhibit re-endothelialisation of the wounded site, causing delayed healing and in-stent thrombosis. Protein drugs, in general, possess cell-specific functions and may therefore inhibit smooth muscle cell proliferation selectively and/or speed-up re-endotheliasation. Due to this prospective, protein drug-eluting stents have attracted considerable research efforts in recent years, and some promising molecules have been reported. However, due to the fragile and susceptible tertiary structure of proteins, loading these macromolecular drugs onto stent surface of effective amount for sustained release of sufficient period of time has been proven to be a challenging task.To address the issues raised above, a unique fabrication method is proposed in the present study to coat proteins with preserved nature state on stent. Delicate proteins were pre-loaded into polysaccharide glassy particles through aqueous phase-aqueous phase emulsion technology without exposing to water-oil interface. The glassy particles are highly resistant to organic solvent and therefore dispensable in it to be coated onto stent with degradable polymer.Bovine Serum Albumin (BSA) was used as a model to carry out this study. Protein-polysaccharide glassy particles were prepared using aqueous phase-aqueous phase emulsion technology and dispersed in PLA solution, then sprayed onto 316L stainless steel stent to fabricate protein-eluting stent. The morphology of stent coating was examined by optical microscope and scanning electron microscopy (SEM). The aggregation of protein before and after formulation was studied by SEC-HPLC. The release kinetics of protein from stent was investigated by shaking in PBS buffer in 37°C, and assaying the release medium using MicroBCA Kit programly. Meanwhile, the effects of polymer, thickness of controlling layer, protein/dextral ratio and protein property on release profile are also investigated.On the basis of protein coating strategy established in the above study, this article discussed the application of EPO—a protein that has angiogenic effect on endothelial cells as VEGF--on stent. The method of testing the bioactivitity of EPO was established, the aggregation of protein before and after formulation was studied, and the in vitro release profile of EPO was studied by assaying the bioactivity of released EPO every day.The results showed that stent coating was smooth and uniform. No protein aggregation was observed during formulation, and protein could be released from stent for more than 50 days. The release rate could be adjusted by selecting polymer matrix, the controlling layer thickness, and the protein/dextran ratio. The EPO-eluting stent prepared by the above method could as well protect the stability of EPO in the formulation and release process and achieve a sustained-release profile.The protein-polysaccharide glassy particles prepared from aqueous phase-aqueous phase emulsion technology can be coated on stent while protecting the stability of protein. Protein can be released in a sustained manner. This method provides a research basis for application of other proteins with therapeutic value on stent.