Toxicity and antitumor activity of liposome-entrapped retinoid Ro13-7410.
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)
McCarthy
D J
DJ
Kettering-Meyer Laboratory, Southern Research Institute, Birmingham, Alabama.
Dollar
G R
GR
Hill
D L
DL
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000633:toxicity*; D001565:Benzoates / Q000008:administration & dosage / Q000494:pharmacology / Q000633:toxicity*; D004337:Drug Carriers; D005260:Female; D006801:Humans; D007942:Leukemia, Experimental / Q000188:drug therapy; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy; D008081:Liposomes; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D012176:Retinoids / Q000008:administration & dosage / Q000494:pharmacology / Q000633:toxicity*
D000970:Antineoplastic Agents; D001565:Benzoates; D004337:Drug Carriers; D008081:Liposomes; D012176:Retinoids; C038864:4-(2-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthalenyl)-1-propenyl)benzoic acid