蛋白药物涂层支架的制备表征与体外释放研究

Preparation,Characterization and In Vitro Release Study of Protein-Eluting Stent

目的:探讨将蛋白大分子药物以较高的担载量涂层于心脏支架,并在不发生蛋白聚集的前提下实现数周之久缓释的方法。方法:将牛血清白蛋白通过稳定的水相-水相乳液技术制备成多糖玻璃体颗粒,并将多糖玻璃体颗粒分散于聚乳酸溶液中喷涂于支架表面制成蛋白涂层支架,在37℃PBS中进行体外释放动力学研究,用SEC-HPLC比较了蛋白涂层支架制备前后蛋白的聚集情况,并用扫描电镜等对蛋白涂层支架表面进行了表征。结果:蛋白涂层支架在电镜观察下外观圆整,表面光滑,制剂过程中未产生蛋白聚集,且能从涂层中缓慢释放达50天以上。结论:稳定的水相-水相乳液技术及其基础上制备的蛋白多糖玻璃体颗粒应用于心脏支架涂层上,能在有效保护蛋白构象的同时实现蛋白的缓释,为具有抗再狭窄活性蛋白应用于心脏支架提供了技术平台。

Objective To prepare protein-eluting stent with high loading capability which preserve protein＇s stability and have protein sustained-release for several weeks. Methods Protein-polysaccharide glassy particles were prepared using aqueous phase-aqueous phase emulsion technology and dispersed in PLA solution, then sprayed onto 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. Results Stent coating was smooth and uniform. No protein aggregation was observed during formulation, and BSA could be released from stent for more than 50 days. Conclusions The protein polysa-ccharide 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 the application of other proteins with therapeutic value on stent.