多柔比星长效注射微球的评价和对小鼠肿瘤的抑制作用

CHARACTERIZATION OF DOXORUBICIN LOADED MICROSPHERES AND ITS TUMOR INHIBITORY EFFECT IN MICE

主要考察了多柔比星(Dox)微球的理化性质、释放特性及其对荷瘤小鼠的抑制作用.以乳酸-羟乙酸共聚物(PLGA)为载体材料,用复乳法(w/o/w)制备载Dox长效注射微球;考察粒径大小、外观、包封率、载药量等理化性质;用紫外分光光度法检测了体外释放溶液中的药物含量,以荷Lewis肺癌小鼠的肿瘤质量和体积为指标观察Dox微球(Dox-MS)瘤内注射给药后的抗肿瘤活性.制备得到的微球球形圆整、分散性好,平均粒径为82.94μm,包封率为92.67%,载药量为9.12%.微球体外第1天释放30.24%,20 d累积释放91.85%.给药8 d后,Dox微球瘤内注射给药组与对照组相比肿瘤平均体积明显减小,抑瘤率与对照组相比具有极显著性差异(P<0.01),但与Dox溶液静脉、瘤内给药组相比无显著性差异.因此Dox微球对小鼠体内Lewis肺癌具有较好的抑制作用,其抑瘤效果与瘤内注射相同剂量的Dox溶液相当,但局部刺激性较小.

The doxorubicin（Dox）--loaded microsphere was prepared, and its physical characteristics, in vitro release behavior and tumor inhibitory effect in mice were evaluated. The microspheres were prepared with poly（lactic-co-glycolic acid） （PLGA） as carrier material by double emulsion （w/o/w） method. Physical characteristics of microspheres, such as mean diameter, morphology, drug entrapment efficiency and loading percent were evaluated. The in vitro release content was determined by ultraviolet spectrophotometry. The volume and weight of tumors were evaluated to determine the antitumor effect of Dox-loaded microspheres injected intratumorally（i, t. ） in mouse with Lewis lung cancer. Microspheres had good shape and dispersive quality. The mean diameter was 82.94 μm, drug entrapment efficiency 92.67%, and loading percentage 9.12%. The cumulative release content was 30.24% on day 1, and 91.85% on day 20. The mean tumor volume of Dox-loaded microspheres （Dox-MS） group was smaller than control. There was significant difference between Dox-MS group and control in tumor growth inhibition（P〈0.01）, but no difference among Dox-MS, Dox i.v. and Dox i. t. groups. Therefore, Dox-MS had good growth inhibitory effect on Lewis cancer in mice, which was similar to that caused by Dox solution i. t.