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目的制备载人骨形态发生蛋白-2(rhBMP-2)的甲基丙烯酸缩水甘油酯右旋糖酐(dex-GMA)凝胶微球并初步考察其体外溶胀、降解、载药与释药特征。方法以液体石蜡为油相,Span-80为乳化剂,采用乳化化学交联技术制备载rhBMP-2的凝胶微球(BMP-HMs)并通过正交设计法优化其制备工艺;观察BMP-HMs形态和粒径,测定其包封率与载药量;用微球的吸水能力表示微球的溶胀率(Rs),扫描电镜观察微球的体外降解,动态观察体外释药特征及其与微球溶胀、降解的关系。结果所制备的BMP-HMs形态规整,粒径40～50μm,分布均匀;rhBMP-2载药量(10.6±4.8)%,包封率(88.9±1.0)%,BMP-HMs冻干剂4℃以下存放6个月性能稳定,但在磷酸盐缓冲液(PBS)中20～40d内可以完全降解。微球Rs随反应促进剂四甲基乙二胺(TEMED)用量的增大而减小,0.3mlTEMED制备的BMP-HMs体外释药实验表明80%的rhBMP-2在前20d左右释放。结论BMP-HMs对rhBMP-2具有确定的缓释作用,并可以通过制备工艺的改变控制其释药。
OBJECTIVE To prepare dex-GMA gel microspheres containing human bone morphogenetic protein-2 (rhBMP-2) and investigate its characteristics of swelling, degradation, drug loading and drug release in vitro. Methods The liquid microspheres (BMP-HMs) containing rhBMP-2 were prepared by emulsion chemical cross-linking technique using liquid paraffin as oil phase and Span-80 as emulsifier. The preparation process of BMP-HMs was optimized by orthogonal design. HMs morphology and particle size, determination of the entrapment efficiency and drug loading; microspheres with water absorption capacity that the microspheres swelling rate (Rs), scanning electron microscopy in vitro degradation of microspheres, dynamic observation of in vitro release characteristics and Microsphere swelling, degradation of the relationship. Results The BMP-HMs prepared in this study had a regular shape with particle sizes of 40-50 μm and uniform distribution. The drug loading of rhBMP-2 was (10.6 ± 4.8)%, encapsulation efficiency (88.9 ± 1.0)%, BMP- Stored below 6 months stable, but in 20 ~ 40d in phosphate buffered saline (PBS) can be completely degraded. The microspheres Rs decreased with the increase of the amount of tetramethylethylenediamine (TEMED). The in vitro release of BMP-HMs prepared with 0.3 ml TEMEM showed that 80% rhBMP-2 was released in the first 20 days. Conclusion BMP-HMs have definite sustained-release effect on rhBMP-2 and can be controlled by the change of preparation process.