肺靶向卡铂明胶微球的研究

目的:为提高卡铂的疗效,降低毒副作用,制备了该药的明胶微球。方法:用乳化法制备卡铂明胶微球,紫外分光光度法测定药物的含量,二阶导数法测定体外释药情况;用静脉注射肿瘤细胞建立了肺肿瘤模型,计算瘤结节数来考察疗效。结果:卡铂明胶微球平均粒径为13-20 μm ,粒径范围5-0～28-6 μm 的微球数占总数的91-8% 。微球平均载药量为23-76%(n=3) 。冰箱、室温和37℃,RH75% 考察3个月,几乎无变化,体外释药符合一级动力学规律,释药T_1/2 比原药延长约10倍。药效学实验表明,卡铂明胶微球对小鼠肺部S180肿瘤生长有明显的抑制作用,抑瘤作用较原药卡铂大大提高。结论:卡铂明胶微球在体内有良好的肺靶向性,对提高药物的疗效,降低药物毒副作用等方面有重大意义。

STUDIES ON LUNG TARGETING GELATIN MICROSPHERES OF CARBOPLATIN

AIM: To improve the treatmemt efficacy and reduce the side effect of carboplatin (CBP), the antitumor drug was incorporated into gelatin microspheres (GMS). METHODS: Lung targeting gelatin microspheres of CBP (CBP-GMS) were prepared by the method of emulsion. The ultraviolet absorption spectrophotometric method was used for the determination of CBP. The method of dynamic dialysis was used in in vitro release of CBP from CBP-GMS. S180 lung neoplasm models were established by iv cancer cell. The number of pulmonary nodules was examined for evaluating the treatment efficacy. RESULTS: The data showed that the mean diameter of CBP-GMS was 13 20 μm, with 91 8% of the microspheres ranging from 5 0 μm to 28 6 μm. The average content of CBP in CBP-GMS was 23 76% and the CBP-GMS were stable for three months stored at 37℃ (relative humidity 75%). The release profile in vitro could be described by first order kinetic equation. The results of therapeutic trials showed that the antitumor effects were significantly increased by injection of CBP-GMS compared with injection of CBP solution in the treatment of mice with lung carcinoma. CONCLUSION: The results indicated that CBP-GMS have a good targeting efficiency in vivo, and the biodegradable CBP-GMS may decrease the side effects of carboplatin and improve its treatment efficacy.