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 H22 HCC were divided into three groups (n = 5), which were respectively intratumorally injected with normal saline (NS), blank microspheres, and EPI-PLA-MS (with 9 mg/kg of EPI). After two weeks the tumors were excised and weighed. Another 15 mice with transplanted 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 exactly.
Results: The MTD of intraperitoneally injected FEPI was 9 mg/kg. The tumour-inhibiting rates was 40.35% and 36.09% when EPI-PLA-MS were administered by intratumoral injection to the mice with subcutaneous H22 HCC. It significantly prolonged the survival time of mice with H22 ascites HCC and the increased life span by 153.49% and 142.22% when EPI-PLA-MS were intraperitoneally administered.
Conclusion: EPI-PLA-MS is a new sustained-release preparation with high-efficacy and low-toxicity in treating HCC and has shown promising prospects when administered locally.