玻璃体内注射用醋酸地塞米松聚丙交酯缓释微球

INTRAVITREALLY INJECTABLE POLY (D,L-LACTIDE) MICROSPHERES CONTAINING DEXAMETHASONE ACETATE FOR SUSTAINED RELEASE

目的 研制玻璃体内注射用醋酸地塞米松聚丙交酯微球 (DA PL MS)及其相关性质 ,并在家兔玻璃体内注射 ,观察治疗实验性增殖性玻璃体视网膜病变 (PVR)的效果。方法 溶剂挥发 萃取法制备DA PL MS ,考察微球的粒径大小与分布、载药量、包封率和体外释放特性 ,用差示扫描量热分析和X 射线粉末衍射分析鉴别物相 ,并考察眼内安全性及组织中的分布。观察巨噬细胞造型白化家兔眼 ,确定玻璃体内注射微球后对PVR的防治效果。结果 微球的平均几何粒径为 6 2 94μm ,跨距为 0 92 ,载药量为 17 5 0 % ,包封率 86 5 2 % ,体外 90d释放约 90 % ,比原药延长约一倍。空球组对治疗PVR无效 ;原药组对治疗PVR有短期作用 ,作用时间为 42d ;微球组药效持久 ,84d时眼底仍清晰 ,无明显增生与牵拉 ,且未发现明显的刺激性及毒性。结论 DA PL MS玻璃体内注射给药有较高的安全性 。

AIM To prepare and evaluate dexamethasone acetate loaded poly ( d,l lactide) microspheres for sustained release in vitro and their therapeutic effect on proliferative vitreoretinopathy in vivo . METHODS The microspheres were prepared by a solvent evaporation/extraction technique. Properties such as geometric mean diameter, span, drug loading, rate of entrapment and release characteristics were evaluated. Differential scanning calorimetry and X ray powder diffractometry were used to identify the physical phase of dexamethasone acetate in poly ( d,l lactide) matrix, and safety in vivo was examined. Effect of drug loaded microspheres on suppression of experimental proliferative vitreoretinopathy was studied in albino rabbit eyes after an intravitreal injection of macrophages. RESULTS The geometric mean diameter and span of the microspheres were 62 9 μm and 0 92, respectively. Drug loading and rate of entrapment of dexamethasone acetate in microspheres were 17 5% and 86 5%, respectively. Differential scanning calorimetry and X ray powder diffractometry showed that dexamethasone acetate dispersed uniformly as molecules in poly ( d,l lactide) matrix. Ninety percent of the dexamethasone acetate was released in vitro from dexamethasone acetate after 48 days, while the same amount released from microspheres took 90 days. Storage under 4℃ in refrigerator or 25℃ in a dessicator at a relative humidity of 75% for 90 days had little effect on the properties of the microspheres. Intravitreal injection of microspheres showed a sustained release and continuous action of dexamethasone acetate for 84 days. After injection of activated macrophages, the groups of blank microspheres and dexamethasone acetate showed proliferation to different extent, while the base of the eye remained clear and no obvious proliferation was observed for the group of microspheres. A significant difference exists between these three groups. CONCLUSION Poly ( d,l lactide) microspheres containing dexamethasone acetate is a potentially promising delivery system for the suppression of proliferative vitreoretinopathy.