肺靶向卡铂囊泡的研究

STUDIES ON LUNG TARGETED NIOSOMES OF CARBOPLATIN

目的 制备卡铂非离子型表面活性剂囊泡 ,以提高卡铂对肺癌的疗效并降低其毒副作用。方法 用薄膜分散法制备卡铂囊泡 ,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。小鼠体内分布试验 ,用iv .S 180肿瘤细胞建立了肺肿瘤模型 ,计算瘤结节数。结果 卡铂囊泡平均粒径为 3 72 μm ,最小粒径为 2 0 μm ,最大粒径为 10 0 μm ,跨距为 0 6 6。卡铂囊泡包封率为 2 9 2 %。体外释药符合双指数方程的规律 ,释药T1/ 2 比原药延长9 14倍。体内分布研究表明 ,卡铂囊泡与原药相比 ,有明显的肺靶向性。卡铂泡囊对小鼠肺脏S 180肿瘤生长较原药的抑瘤作用有明显提高。

AIM To improve the treatmemt efficacy and reduce the side effect of carboplatin (CBP), the antitumor drug was incorporated into niosomes (NS). METHODS Lung targeted niosomes of CBP (CBP-NS) were prepared by the method of hand shaking. The ultraviolet absorption spectrophotometric method was used for the determination of CBP. The method of dynamic dialysis was used for in vitro release of CBP from CBP-NS. The S-180 lung neoplasms models were established by iv cancer cells in mice. The number of pulmonary nodules was examined for evaluating the therapeutic efficacy. RESULTS The data showed that the mean diameter of CBP-NS was 3 72 μm, with a span of 0 66. The entrapment ratio of CBP in CBP-NS was 29 2% and the CBP-NS were stable for three months stored at 3℃-5℃, 15℃-25℃ or 37℃ (relative humidity 75%). The release profile in vitro could be described by a biexpotential equation. The calculated values of the three targeting parameters indicated that CBP-NS showed good targeting efficiency. The results of therapeutic trials showed that the antitumor effects were significantly increased by injection of CBP-NS compared with CBP in the treatment of mice with lung carcinoma. CONCLUSION The results indicated that CBP-NS have good targeting efficiency in vivo , and the biodegradable CBP-NS may decrease the side effects of carboplatin and improve its therapeutic efficacy.