rhBMP-2/聚乳酸与聚乙醇酸共聚物载药微球的制备及成骨活性研究

Preparation and osteogenic activity of rhBMP-2 loaded/poly(lactic-co-glycolic acid) microsphere

目的制备一种具有良好降解性和成骨活性可注射的rhBMP-2载体材料。方法采用复乳-溶剂蒸发技术制备携载rhBMP-2的聚乳酸与聚乙醇酸共聚物P(LGA)微球。测定材料的制备参数及其特性,包括材料的形貌、载药率、释药速度,并将载药微球植入鼠股部肌袋,通过X线、组织学评价载体材料的异位成骨能力。结果载药微球粒径为(253±64)μm,载药率0.52%±0.14%,载药微球rhBMP-2体外释放24h时为15.2%±0.8%,随后呈持续缓慢释放,28d时总计达48.6%±5.3%。载药微球植入鼠股部肌袋4周,材料周围有明显的骨形成。结论载有rhBMP-2的PLGA微球具有良好的缓释效果和生物活性,是一种较为理想的生长因子载体材料和释放系统。

Objective To preparate a type of carrier material characterized with good degradation and active osteogenesis. Methods The rhBMP-2 loaded microspheres with biodegradable poly （lactide-co-glycolide） microspheres （PLGA） were prepared by a double-emulsion,solvent-extraction [（water-in-oil）-in-water] technique. The protein release kinetics and the degradation of PLGA microspheres were determined in vitro up to 28 days. The rhBMP-2 loaded or simple PLGA microspheres were implanted bilaterally into muscle pouches of rats so as to observe ectopic bone formation histologically. Results The diameter of PLGA microsphere was （253 ± 64） μm,the load density of rhBMP-2 was 0.52 % ± 0.14 %. The sustained release implants,showing 15,2 % ± 0.8 % initial release ,followed by a prolonged release for 28 days. Significant bone growth was observed in the BMP-2 treated group,whih in the BMP-2-free group bone formation was not found. Conclusion With good osteogenetic activity, the biodegradable PLGA microsphere system can be served as cartier for sustained release of rhBMP-2.