胶原酶缓释微球的研究

Research on Collagenase-loaded Microspheres

目的:本实验旨在开发一种胶原酶缓释微球制剂,用以治疗手掌腱膜挛缩症,以减小现有水针剂的不足。方法:利用水相-水相乳化法和低温冷冻相分离法两种方法制备载药颗粒,分别将其包裹于PLGA微球内,制备成胶原酶微球,并用扫描电镜考察其表面形态,对其粒径进行统计学分析,测定体外释放行为并比较。结果:两种方法制备的微球表面光滑圆整,都可以达到缓释的效果,一个星期内释药完全。水相-水相乳化法制备的微球比低温冷冻相分离制备的微球粒径大,且具有统计学差异(P<0.05)。水相-水相乳化法制备的微球粒径较均一,其体外释放更加平缓,突释较小。结论:本研究制得的胶原酶微球能实现理想的体外缓释效果,解决了现有技术中胶原酶粉针剂型快速释放并分散的问题。

Objective： To research the sustained release of collagenase-loaded microspheres to treat Dupuytren＇s disease, as well as to compensate the shortcoming of powder injection. Methods： Aqueous-aqueous emulsion method and freezing phase separation method were used to make micro-particles respectively. Then the particles were encapsulated into PLGA microspheres. The microspheres were observed by SEM. Statistical analysis of the sizes were made between the two methods. And in vitro release curves of microspheres were tested to compare the two methods. Results： The microspheres prepared by the two different methods were spherical. Sustained release of microspheres by two different ways could be achieved. The sizes of microspheres by aqueous-aqueous emulsion method were significantly larger than that of the freezing phase separation method（P〈0.05）. The release of collagenase from the microspheres by aqueous-aqueous emulsion method was more moderate with low burst release. Conclusion： Collagenase microspheres would achieve sustained release for one week to solve the problem of fast drug diffusion after powder injection.