表柔比星壳聚糖微球联合微波消融治疗小鼠肝移植瘤

Epirubicin-loaded chitosan microspheres combined with microwave coagulation for treating hepatocellular carcinoma in mice

背景:原发性肝癌的手术切除率较低,肝癌的局部治疗成为重要手段。经皮微波消融治疗能达到原位灭活的目的,但不能彻底杀灭瘤细胞。缓释剂型化疗药物可形成局部较高药物浓度及发挥较持久作用,目前已多被应用于原发性肝癌的治疗。目的:观察负载表柔比星的壳聚糖微球联合微波消融局部治疗荷肝癌小鼠皮下移植瘤的效果。方法:采用W/O型乳化-固化法制备表柔比星-壳聚糖微球,扫描电镜观察壳聚糖微球的表面形态,粒径大小。紫外分光光度计分析载药微球的包封率、载药量及药物累积释放率。将24只H22皮下肝癌荷瘤小鼠分成4组,各组皮下肝癌肿瘤分给予以下治疗:单纯微波治疗;微波治疗后第2天给予瘤内注射生理盐水;微波治疗后给予瘤内注射表柔比星;微波治疗后联合瘤内注射载药微球,监测荷瘤小鼠肿瘤体积变化并计算抑瘤率。结果与结论:壳聚糖微球平均粒径约为105μm,粒径大小较一致,包封率约为80%,载药率约为11%,2周的累积缓释率为84%。微波联合瘤内注射生理盐水、表柔比星、载药微球的抑瘤率分别为8%,20%,47%。表明壳聚糖微球是一种有效的表柔比星局部缓释剂型,联合微波消融治疗有较强的抑瘤作用。

BACKGROUND：The surgical resection rate of primary hepatic carcinoma is low,thus,the local treatment arose more attention.Microwave coagulation therapy can inactivate rather than kill the hepatic carcinoma cells.Slow-release chemotherapy has been used in treating primary hepatic carcinoma because it can form local high concentrations and last for a long time.OBJECTIVE：To observe the therapeutic effect of epirubicin-loaded chitosan microspheres combined with microwave coagulation on treating hepatocellular carcinoma in mice.METHODS：Epirubicin-loaded chitosan microspheres were prepared by using emulsion-chemical cross linking technique.The surface morphology and particles size of chitosan microspheres were observed by scanning electron microscope.Ultraviolet spectrophotometer was used to analyze the entrapment efficiency,entrapment efficiency and cumulative release rates of epirubicin-loaded chitosan microspheres.Totally 24 mice with transplanted subcutaneous H22 HCC were divided into 4 groups,which were respectively treated by microwave coagulation therapy,intratumoral injected with physiological saline after microwave coagulation therapy,intratumoral injected with epirubicin after microwave coagulation therapy,intratumoral injected with epirubicin-loaded chitosan microspheres after microwave coagulation therapy.The tumor inhibitory rate was calculated.RESULTS AND CONCLUSION：The average diameter of chitosan microsphere was 105 μm,with uniformed particle diameter.The ratio of drug loading was 11% and the entrapment was 80%.The in vitro drug cumulative release rate was 84% after 2 weeks.The tumor inhibitory rates of the microwave coagulation combined with physiological saline,epirubicin,and drug carried microspheres groups were 8%,20%,and 47%.It suggested that chitosan microsphere is a safe and effective slow-release dosage form,which exhibits strong anti-tumor effect when combined with microwave treatment.