4-(2-(5-6-7-8-tetrahydro-5-5-8-8-tetramethyl-2-naphthalenyl)-1-propenyl)benzoic-acid and Leukemia--Myeloid--Acute

We compared the toxicity of free and liposome-entrapped retinoid, Ro13-7410 in C2DF1 mice. Mice received 7 daily i.p. injections of liposome-entrapped Ro13-7410 at doses of 5, 10, 100, 500, or 1000 micrograms/kg bw/day. For comparison, two groups of mice were used as controls, one group received Ro13-7410 in corn oil and a second group received liposome-entrapped Ro13-7410 that had been solubilized with detergent. The liposomes were then tested for chemotherapeutic activity against human myelocytic leukemia (HL-60/MRI) implanted in athymic NCr-nu mice. The doses used in the chemotherapy experiment (20, 50, and 100 micrograms/kg bw/day) were selected based on the results of the toxicity experiment in CD2F1 mice. CD2F1 mice were marginally protected from toxicity after receiving retinoid in liposomes relative to controls. There were 2/5 survivors in the 1000 micrograms/kg bw/day Ro13-7410-liposome group after 7 daily i.p. doses compared to 0/5 for both the corn oil and solubilized liposome groups, and 4/5 survivors in the 500 micrograms/kg bw/day Ro13-7410-liposome group after 7 daily i.p. doses compared to 2/5 for both the corn oil and solubilized liposome groups. We observed no dramatic differences in toxicity among the treatment groups over the range of doses administered. There were 2/6 long-term tumor-free survivors in athymic mice receiving liposome-entrapped retinoid, at 50 micrograms/kg bw/day for 7 days, compared with 0/6 and 0/9 survivors in groups receiving empty liposomes or no treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Animals; Antineoplastic Agents; Benzoates; Drug Carriers; Female; Humans; Leukemia, Experimental; Leukemia, Myeloid, Acute; Liposomes; Male; Mice; Mice, Inbred Strains; Mice, Nude; Neoplasm Transplantation; Retinoids