Treatment of Hepatocellular Carcinoma in Mice with Locally Administered Epirubicin-loaded Poly(D,L)-lactic Acid Microspheres

摘要

[中文文摘]目的研究表柔比星-聚乳酸缓释微球(EPI-PLA-MS)局部给药治疗肝癌的效果。方法复乳-溶剂挥发法制备EPI-PLA-MS。将40只昆明小鼠随机分为5组,每组8只,分别腹腔注射不同剂量的游离表柔比星(FEPI),计算最大耐受量(MTD)。H22皮下实体瘤肝癌荷瘤小鼠3组,每组5只,分别用生理盐水(normalsaline,NS)、空白微球和含药微球(含EPI9mg/kg)瘤内注射给药,2周后取瘤称重。H22腹水型肝癌荷瘤小鼠3组,每组5只,分别用NS、空白微球和含药微球(含EPI9mg/kg)腹腔注射给药,计算动物生命延长率。结果FEPI腹腔注射的MTD为9mg/kg。EPI-PLA-MS瘤内给药后含药微球组和空白微球组的抑瘤率分别为40.35%和36.09%。腹腔给药后能显著延长荷瘤鼠的生存时间,含药微球组和空白微球组生命延长率分别为153.49%和142.22%。结论EPI-PLA-MS是一种有效低毒的药物新剂型,在局部治疗肝癌方面具有良好的临床应用前景。[英文文摘]Objective To study the effectiveness of treating hepatocellular carcinoma(HCC)in mice with locally administered epirubicin-loaded poly(D,L)-lactic acid microspheres(EPI-PLA-MS).Methods EPI-PLA-MS was prepared with double emulsion solvent evaporation technique.Five groups of mice(n=8 in each group)were intraperitoneally injected with five different doses of free epirubicin(FEPI),and the maximum tolerated dose(MTD)was calculated.Then 15 mice with transplanted subcutaneous H 22 HCC were divided into three group s ( n = 5) , which were respectively intratumorally injected with normal saline (NS) , blank micro-spheres, and EPI-PLA-MS (with 9mg/kg of EPI) 1 After two weeks the tumorswere excised and weighed1 Another 15 mice with transp lanted H22 ascites HCC were divided into three groups (n=5) , which were intraperitonealy injected with the same drugs, and the increased life span were registered exactly1 Resutls　TheMTD of intraperito neally injected FEPIwas 9mg/kg1 The tumour inhibiting rateswas 40135% and 36109% when EPI-PLA-MS were administered by intratumoral injection to the mice with subcutaneous H22 HCC1 It significantly p rolonged the survival time of mice with H22 ascites HCC and the increased life span by 153149% and 142122% when EPI-PLA-MS were intraperitoneally administered1 Conclusion　EPI-PLA-MS is a new sustained release preparation with high-ef-ficacy and low-toxicity in treating HCC and has shown promising prospects when administerd locally.