抗脑胶质瘤缓释植入剂体外释药影响因素研究

Study on Influencing Factors of the in Vitro Release Rate of Doxorubicin Hydrochloride Sustained Release Implants for Glioma

目的研究影响抗脑胶质瘤药物盐酸多柔比星缓释植入剂体外释药的因素,为动物药效学研究提供依据。方法以聚乳酸-羟基乙酸(PLGA)为载体与盐酸多柔比星混合制成缓释植入剂,采用UV测定其体外释放度。考察聚乳酸-羟基乙酸共聚物组成、聚乳酸-羟基乙酸相对分子质量(Mw)、载药量等因素对缓释植入剂体外释放度的影响。结果载药量10%的植入剂释药速度明显快于5%的植入剂;随着共聚物组成中羟基乙酸比例的增加,释药速度明显加快,LA-GA为50∶50的植入剂35d时累积释放度达90%,而75∶25的植入剂仅为60%;聚乳酸-羟基乙酸相对分子质量与释药速度成反比,Mw=20 748的植入剂释药速度明显快于Mw=30 834的植入剂。结论聚乳酸-羟基乙酸共聚物组成、聚乳酸-羟基乙酸相对分子质量、载药量是影响缓释植入剂体外释药的因素,其中共聚物组成和相对分子质量是主要的影响因素。通过调节共聚物组成和相对分子质量可以很好地控制药物的释放速度。

OBJECTIVE To study the factors affecting the in vitro release rate of doxorubicin hydrochloride sustained release im- plants for glioma to provide information for pharmacodynamic evaluation in animals. METHODS The implants were prepared by in- corporating doxorubicin hydrochloride into poly（lactide-co-glycolide） （PLGA） matrix. The in vitro release rate of the implants was de- termined by UV. The copolymer ratio and molecular weight （Mw） of PLGA,and the drug loading were examined to study their effects on the in vitro release rate of the implants. RESULTS The release rate of 10% drug-loaded implants was greater than that of 5% drug-loaded ones, and it was enhanced by an increase in the proportion of copolymerized glycollic acid in PLGA. The cumulative release rate of the implants with LA-GA ratio of 50：50 was 90% at 35 d,while that of the implants with LA-GA ratio of 75：25 was only about 60%. The molecular weight of PLGA was inversely proportional to the release rate of the implants. The release rate of the implants with Mw of 20 748 was greater than that with Mw of 30 834. CONCLUSION The factors affecting the in vitro release rate of the implants include the copolymer ratio of PLGA, the molecular weight of PLGA and the drug loading, among which the copolymer ratio and molecu- lar weight of PLGA are the major factors. The drug release rate of the implants can be well controlled by regulating the copolymer ratio and molecular weight of PLGA matrix.