Therapy of mouse mammary carcinomas with vincristine and doxorubicin encapsulated in sterically stabilized liposomes

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Abstract
This study tested the therapeutic effects of vincristine sulfate and doxorubicin hydrochloride, each drug in 2 different formulations: (i) as a solution in saline, and (ii) encapsulated in sterically stabilized, long-circulating liposomes composed of hydroge-natedsoy-phosphatidylcholine/cholesterol/polyethylene-glycer-ol-distearoyl- phosphatidylethanolamine. The 4 drug preparations were used to treat s.c. implants of the mouse mammary carcinoma MC2. The drugs were given by i.v. injection over 15 to 18 days, starting 3 days after tumor implantation. The single-drug therapeutic effects of vincristine (S-VCR) and doxorubicin (Doxil) in liposomes were compared, and the 2 preparations were also tested in alternate and in simultaneous combinations. These new liposome formulations of vincristine and doxorubicin were significantly more effective than the free drugs in curing the mice. Alternate, semi-weekly injection of both drugs gave the best therapeutic effect. Prolonged circulation time with increased accumulation in tumors are considered likely reasons for the improved therapeutic efficacy of both drugs when encapsulated in these liposomes.