Treatment of intravenously implanted lewis lung carcinoma with liposome-encapsulated cytosine arabinoside and non-specific immunotherapy

Abstract

Liposomes have been used as biological carriers of anti-tumor drugs, and their potential use has been tested using various mouse tumors. In this study, we describe a potential role of liposome-encapsulated 1-β-D-arabinofuranosyl-cytosine (Ara-C) with a mouse solid lung tumor model. Non-encapsulated Ara-C at 25 mg/kg dose by the intraperitoneal (i.p.) route on days 1, 4 and 7 had no improving effect on the average survival time of tumor-bearing mice compared to untreated control mice. However, the same dose of Ara-C encapsulated in multilamellar liposomes (MLV) improved the average survival of tumor-bearing mice by 60 to 80%. Ara-C was encapsulated more efficiently when DSPC or DPPC MLV were prepared at temperatures below their respective transition temperatures. DSPC and DPPC MLV prepared at 25°C and DPPC MLV prepared at 50°C were equally effective for in vivo therapy, while DSPC MLV prepared at 60°C were not as effective. Non-specific immunotherapy using BCG (Bacillus Calmette-Guérin, Mycobacterium tuberculosis) and CP (Corynebacterium parvum) was effective, particularly when injected by the intravenous (i.v.) route, in prolonging the average survival of tumor-bearing mice. A combination of either i.v. BCG or i.p. CP with liposome therapy gave no further improvement in the average survival of tumor-bearing mice. However, a combination of either i.p. BCG od i.v. CP with liposome therapy was somewhat more effective than either liposome therapy or immunotherapy alone.