Experimental Study In The Treatment Of Hepatocellular Carcinoma With Epirubicin-loaded Poly(D,L)-lactic Acid Microspheres Locally Administered

Object To prepare the epirubicin-loaded Poly(D,L)-lactic acid microsphere (EPI-PLA-MS), and evaluate its physicochemical properties in vitro and its effectivity and toxicity in vivo for local therapy to hepatocellular carcinoma (HCC). The superiority and mechanisms of the sustained-release microsphere (MS) compared to free epirubicin (FEPI) and local therapy compared to systemic therapy were inquired. To provide the warranty for clinical application.Methods 1. EPI-PLA-MS was prepared with double emulsion-solvent evaporation technique, taking EPI as the model medicine and PLA as the carrier. Its morphology and size was observed with electronic microscopy, and its drug loading, encapsulation efficiency and drug-release rate were measured.2. Mice models with transplanted subcutaneous H22 HCC were build up. NS, blank microspheres and three different doses of microspheres with 4.5, 9 and 18 mg/kg of EPI were intratumorally injected into five groups of mice, microspheres with 9 mg/kg of EPI were also injected intraperitonealy into the sixth group. After two weeks the tumors were excised and weighed, and the tumor inhibiting rates of the test groups were calculated. Also they were sliced up and dyed with hematoxylin and eosin, and examined generally pathologically.3. Mice models with transplanted H22 ascites HCC were made. Seven groups of mice were injected intraperitonealy with blank microspheres, NS, three different doses of microspheres with 9, 18, 36 mg/kg of EPI, FEPI (9mg/kg) and the combining of microspheres with EPI 4.5 mg/kg and FEPI (4.5 mg/kg). And animals'death was numbered exactly. The average survival time, the median survival time and the percent increase in life span of all the test groups were calculated. Also the maximum...