Multivesicular liposomes containing bleomycin for subcutaneous administration

Summary Optimal cancer treatment with cell-cycle-specific agents requires maintenance of a cytotoxic drug level for a prolonged period. We explored the use of multivesicular liposomes as a slow-release depot of bleomycin for systemic administration via the s. c. route. The average volume-adjusted liposome size was 19.1 m, the half-life of leakage in human plasma was 32.1 h, and the half-life of s. c. liposomal bleomycin was 31.8 h. When tested against the s. c. B-16 melanoma model in BDF₁ mice, the therapeutic index of single-dose bleomycin given s.c. was significantly improved when the drug was encapsulated in multivesicular liposomes. The efficacy was improved as assessed by both inhibition of tumor growth and increased life span, and the toxicity appeared to be decreased.Supported by grants CH-484 (American Cancer Society) and CA-01082 (National Cancer Institute, PHS), and by the Clayton Foundation for Research, California Division, and the University of California Cancer Research Coordinating Committee