平阳霉素白蛋白微球的制备及其体外释药的实验研究

An Experimental Study on the Preparation and Drug Sustained Release Characteristics of Pingyangmycin Albumin Microspheres

目的 制备平阳霉素白蛋白微球(PYM_AMS),用于治疗动静脉血管畸形。方法 采用乳化热固化法,在 140℃制备出PYM_AMS,并考察其理化性质:通过超声测定强度,激光散射粒径分析仪测定粒径大小,紫外分光光度 法测定载药率、包封率和体外模拟累积释放度。把制备好的PYM_AMS分装后,经60Co辐照灭菌。并通过放置于冰 箱(3～5℃)、室温(15～25℃)和37℃,RH75%条件下放置3月,考察其稳定性。结果 制备的PYM_AMS平均粒径 为139.422μm,56～251μm的微球约占总数的80%,载药率为26.47%,包封率为84.3%;5h内药物快速释放,之后 进入缓慢过程,24h累积释放率为88.65%,t50为1.5h;分装后,经60Co辐照灭菌;性质稳定,经5号、6号药典筛筛分 后,可获得125～180μm的微球。结论 制备的PYM_AMS载药量高,具有缓释效果,能够达到治疗动静脉畸形的要 求。

Objective The aim of this study was to prepare Pingyangmycin Albumin Microspheres (PYM-AMS) for arteriovenous malformations treatment.Methods PYM-AMS was prepared at 140 ℃ by the method of emulsification-heat solidification and its characteristics were evaluated, such as morphosis, particle size, drug loading (DL%), encapsulation efficiency (EE%), stability and drug sustained-releasing in vitro. After being packaged, PYM-AMS were sterilized with 13.7 kGy of +{60}Co. Small samples of PYM-AMS were packaged in small bottles and stored at 3～5 ℃、15～25 ℃、37 ℃ for 3 months, then checked the change of morphology、DL、EE and the release rate.Results The surface of particles was smooth and integrated. The average diameter of PYM-AMS particles was 139.422 μm and 80% was in the range of 56～251 μm. The mean DL% and EE% were 26.47% and 84.3%, respectively. PYM released fast in 5 h, but then released slowly. 88.65% drugs were released in 24 h, and t_{50} was 1.5 h. There was no obvious change of the morphology、DL、EE and the release rate of PYM-AMS stored at 3～5 ℃、15～25 ℃、37 ℃for 3 months.Conclusion PYM-AMS prepared in this study had sustained-release effect, high drug loading and high stability. Albumin is a good carrier of PYM embolization agent.