Intratumoral Chemotherapy with an Implantable Collagen Film Impregnated with Epirubicin-loaded Polylactic Acid Microspheres Inhibits Tumor Growth in Hepatocellular Carcinoma Xenografts
- 材料学院－已发表论文 
[中文文摘]制备用于实体肿瘤局部治疗的植入型表阿霉素缓释药膜。采用复乳-溶剂挥发法制备聚乳酸载表阿霉素缓释微球,用交联复合法制备含载药微球的植入型胶原药膜;用扫描、透射电镜、共聚焦及粒度仪等考察微球和药膜的形貌、结构、粒径及体外释放;用H22肝癌荷瘤动物模型评价其体内抑瘤效果。结果:载药微球粒径分布均匀,外观圆整,平均粒径为5.81μm;微球的载药量4.39%,包裹率为37.2%;10h内载药微球在模拟体液中的累积释放率为35%;腹腔注射载药微球与瘤体局部植入胶原药膜对H22肝癌均有明显的抑瘤效果;微球注射与药膜植入两种不同给药方式对H22肝癌抑瘤效果也存在显著性差异(P<0.05)。植入型载表阿霉素缓释胶原膜具有良好的药物局部缓释特性,在肿瘤的术后局部治疗方面具有良好的临床应用前景。[英文文摘]Drug-releasing implants delivering chemotherapeutic agents can provide promising local therapy to patients with malignant disorders.The purpose of the present study was to develop implantable collagen film impregnated with epirubicin-loaded polylactic acid(PLA) microspheres(EPI-PM) for intratumoral administration in solid tumors.EPI-PM was prepared by double emulsion-solvent evaporation method,and the microspheres were further incorporated in biodegradable chemically cross-linked collagen to formulate implantable collagen film. The microspheres were characterized by scanning electron microscope , transmission electron microscope and laser confocus microscopy. In vitro release of epirubicin was examined by ultraviolet spectrophotometry. Transplantable murine hepatoma 22 (H22) model was used to evaluate the effects of EPI-PMor collagen film impregnated with EPI-PMon murine liver cancer.The results indicated that the epirubicin was well incorporated and dispersed homogeneously in PLA. The EPI-PM was uniformly spherical with average diameter of 5181μm, drug loading of 4139% , and embedding ratio of 3712%. The cumulative drug release rate of EPI2PM was 35 % in analog body fluid at the 10h. The tumor growth rate was significantly inhibited by intraperitonal injection of EPI2PMor intratumoral implantation of collagen film impregnated.