骨形态发生蛋白2/聚乳酸缓释微球的制备及表征

背景：聚乳酸具有良好的生物相容性，是优良的药物缓释载体。 目的：制备重组人骨形态发生蛋白2/聚乳酸缓释微球，考察其理化特性。 方法：采用复乳溶剂挥发法制备重组人骨形态发生蛋白2/聚乳酸缓释微球，进行扫描电镜、激光粒度、Zeta电位、溶胀性能检测及采用ELISA试剂盒检测包封率、载药率及体外释药率。 结果与结论：扫描电镜见重组人骨形态发生蛋白2/聚乳酸缓释微球微球近似圆形，形态较规则，分散性较好，表面光滑。激光粒度分析重组人骨形态发生蛋白2/聚乳酸缓释微球微平均粒径839.6 nm，Zeta电位（-32.93±3.74）mV，微球溶胀系数1.157±0.059，包封率及载药率分别为（88.943±2.878）%，（0.026±0.001）%；微球在第1天释药约10.199%，随后释药较恒定，至第19天累计释药率为54.643%。说明制备出的重组人骨形态发生蛋白2/聚乳酸缓释微球的粒径达到中华人民共和国药典第10版二部关于亚微球的定义标准及包封率不低于80%的要求，并且在体外具有很好的缓释功能。

Preparation and characterization of recombinant human bone morphogenetic protein-2/ poly lactic acid sustained release microspheres

BACKGROUND： Poly lactic acid as an excellent delivery has good biocompatibility.
OBJECTIVE： To prepare recombinant human bone morphogenetic protein-2 （rhBMP-2）/poly lactic acid （PLA） sustained release microspheres, and to study its physical and chemical properties.
METHODS： The rhBMP-2/PLA sustained release microspheres were prepared using w/o/w solvent evaporation method. Scanning electron microscopy, laser particle size, zeta potential, and swelling properties were detected. ELISA kit was utilized for measurement of encapsulation efficiency, drug-loading rate and in vitro drug release rate.
RESULTS AND CONCLUSION： Under the scanning electron microscope, rhBMP-2/PLA sustained release microspheres were approximately circle with excellent dispersion. The uniform spheres were visible with a mean particle size of 839.6 nm. The zeta potential were （-32.93±3.74） mV. The swelling coefficient was 1.157±0.059. The drug-loading rate and encapsulation efficiency of rhBMP-2/PLA sustained release microspheres were （88.943±2.878）% and （0.026±0.001）% respectively. The drug release rate at 1 day was about 10.199%, then the drug release was relatively constant, and till 19 days, the cumulative drug release rate was 54.643%. These findings indicate that the constructed rhBMP-2/PLA sustained release microspheres meet the requirement of the Chinese Pharmacopoeia （10th edition） that the encapsulation efficiency is not less than 80% and the microspheres have a good slow-release function in vitro.