THERAPY OF MOUSE MAMMARY CARCINOMAS WITH VINCRISTINE AND DOXORUBICIN ENCAPSULATED IN STERICALLY STABILIZED LIPOSOMES

This study tested the therapeutic effects of vincristine sulfate and d oxorubicin hydrochloride, each drug in 2 different formulations: (i) a s a solution in saline, and (ii) encapsulated in sterically stabilized , long-circulating liposomes composed of hydrogenated ene-glycer-ol-di stearoyl-phosphatidylethanoiamine. The 4 drug preparations were used t o treat s.c. implants of the mouse mammary carcinoma MC2. The drugs we re given by i.v. injection over 15 to 18 days, starting 3 days after t umor 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 combina tions. These new liposome formulations of vincristine and doxorubicin were significantly more effective than the free drugs in curing the mi ce. Alternate, semi-weekly injection of both drugs gave the best thera peutic effect. Prolonged circulation time with increased accumulation in tumors are considered likely reasons for the improved therapeutic e fficacy of both drugs when encapsulated in these liposomes. (C) 1993 W iley-Liss, Inc.