注射用醋酸地塞米松缓释微球体内外评价及生物相容性考察

Investigation on in vitro and in vivo Characteristics and Biocompatibility of Dexamethasone acetate-PLGA Microspheres for Injection

目的制备醋酸地塞米松缓释微球并进行体内外评价及生物相容性考察。方法采用乳化-溶剂挥发法制备微球,并以形态、粒径、载药量、包封率及体外释放为指标对其进行体外评价,同时探讨其体外释药机制;测定皮下注射微球后体内血药浓度,考察微球的体内释放情况;通过考察关节腔注射微球后的组织变化评价微球的组织相容性。结果微球平均粒径小于10μm,包封率高于90%,突释小于7%,体内外均可持续释放一个月左右,且重现性试验中各指标的RSD值均小于3·75%;关节腔注射微球后16d内未见炎症发生,说明微球的组织相容性好。结论本实验所制微球各方面性质均较好,适合关节腔注射。

OBJECTIVE To prepare PLGA microspheres containing dexamethasone acetate and evaluate their characteristics and biocompatibility. METHODS The microspheres were prepared by solvent evaporation method, and were evaluated in vitro by responses such as morphology, particle size, encapsulation, drug loading, burst effect and in vitro release. With dexamethasone acetate suspension as reference standard, the release of the microspheres in vivo was evaluated. The biocompatibility of the microspheres was also investigated. RESISTS The encapsulation of microspheres was higher than 90%, with the burst release lower than 7% and the particle size was smaller than 10 μm. The release of microspheres lasted about one month both in vitro and in vivo while the relative bioavailability was higher than 100%. The RSDs of all respones were smaller than 3.75 %, and there were no inflammatory responses observed during the experiment, CONCLUSION Microspheres are suitable for intra-articular administration.