球结膜下注射用西罗莫司缓释微球的制备及其体外释药性能

Preparation and sustained release properties of sirolimus-loaded microspheres for subconjunctival injection in vitro

目的使用3-羟基丁酸-co-3-羟基戊酸共聚物制备西罗莫司缓释微球,为预防和治疗角膜移植术后免疫排斥反应奠定基础。方法采用乳化-溶剂挥发法制备微球,正交实验法优化,测得载药量、包封率等指标,结合光镜观察其形态特征,得出最佳制备条件后,模拟眼内前房环境检测其体外释药性能。结果微球制备工艺稳定,重复性好。微球成球率高,形态圆整,表面光滑,载药量为(37.34±1.25)%,包封率为(99.63±0.93)%,能够在体外稳定缓释,500 h累积释药率为71%。结论西罗莫司缓释微球表征良好,载药量、包封率较高,有望发挥稳定释药的临床作用。

AIM To prepare microspheres for sustained release of sirolimus using the polymers poly （3-hydroxybutyrate-co-3-hydroxyvalerate） in order to provide a foundation for the prevention and treatment of immunological rejection after corneal transplantation. METHODS The microspheres were prepared by an oil-in- water （O/W） emulsion-solvent evaporation method under orthogonal design. Drug loading rate and entrapment rate of microspheres were measured, and combined with morphological characteristics, the preparation technology was optimized. The experimental results were applied to the aqueous humor simulation environment for detecting sustained release properties in vitro. RESULTS The preparation technology was stable and feasible. Microspheres presented a smooth and regular spherical surfaces with drug loading rate of （37.34 ±1.25） % and entrapment rate of （99.63 ± 0.93） %, which enabled the sustained release of the drug in vitro, and the accumulated release percentage were reached 71% after 500 h. CONCLUSION With the characteristics of well spherical shape, high microspheres would exert drug loading rate and entrapment rate, the sirolimus-loaded sustained-release a stable sustained release effect in clinics.