Increased therapeutic efficiency of a lipid-soluble alkylating agent incorporated in liposomes

Abstract

Summary.-A highly hydrophobic alkylating agent, 1-N,N-bis(beta-bromoethyl) amino-3-methylnaphthalene, given as the free drug in oil, cured a substantial proportion of mice bearing the PC6 myeloma in the dose range 2-7 mg/kg. However, these doses were toxic, and the LD50 was 6-7 mg/kg. When incorporated in liposomes, similar curative effects were obtained at doses of 10-41 mg/kg without material toxicity, even at the highest dose. Liposome entrapment therefore greatly increases the therapeutic efficiency of this agent.

Liposomes as Carrier of Methyl-GAG

“…cytosine arabinoside [Mayhew et al, 1979;Patel and Baldeschwieler, 1984] as well as for water-insoluble agents, e.g. NSC-251 635 [Brassinne et al, 1983], and highly hydrophobic alkylating agents [Babbage and Berenbaum, 1982]. In the present study, we describe for the first time the preparation and the stability of liposomes containing methyl-GAG, the determination of in vitro activity and com pare the therapeutic efficacy and the toxicity of these liposomes against free methyl-GAG in the murine leukemias P 388, L 1210 and Lewis lung carcinoma.…”