摘要
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。
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. EPIPM 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 mierospheres 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 hepetoma 22 （H22） model was used to evaluate the effects of EPI-PM or collagen film impregnated with EPI-PM on 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 5.81μm, drug loading of 4.39 %, and embedding ratio of 37.2 %. The Cumulative drug release rate of EPI-PM was 35% in analog body fluid at the lOh. The tumor growth rate was significantly inhibited by intrapefitonal injection of EPI-PM or intratumoral implantation of collagen film impregnated with EPI-PM. A significant difference was shown in tumor inhibiting rate between intratumorally implanted group and intraperitonal injection group （ P 〈 0.05）. These results suggests that the collagen film impregnated with EPI-PM show potential for localized controlled drug delivery applications and are suitable for postoperative chemotherapy of cancers.
出处
《中国生物医学工程学报》
CAS
CSCD
北大核心
2008年第4期586-590,596,共6页
Chinese Journal of Biomedical Engineering
基金
国家重大科学研究计划项目(2006CB933300)
福建省自然科学基金(C0610045)
厦门市科技计划项目(3502Z20055007)
厦门市科技创新资金项目(3502Z20041029)
关键词
表阿霉素
聚乳酸
胶原
植入型缓释药膜
肿瘤化疗
epirubicin
polylactic acid
collagen
implantable drug delivery system
tumor chemothrapy
