Absorption characteristics of the lipophilic prodrug of mitomycin C from injected liposomes or an emulsion.
Mitomycin C (MMC) is amphiphilic and so cannot be incorporated into lipoidal delivery systems. To develop a lipoidal delivery system, its prodrug, nonyloxycarbonyl MMC, was formulated in liposomes and in o/w emulsions and the usefulness of these formulations was evaluated. After injection into the rat thigh muscle, MMC was rapidly absorbed regardless of the dosage form. However, the prodrug was retained at the injection site for considerably longer when formulated in a lipid dispersion system. The accumulation of MMC at regional lymph nodes was also investigated and whereas free MMC arrived at and disappeared from the lymph nodes almost immediately after injection, the prodrug arrived at an early stage and its concentration decreased only gradually, remaining fairly high 2 h after injection. Liposomal lipids appeared to accumulate at the lymph nodes to a greater degree than o/w emulsions. It is suggested that the combination of lipidic carrier devices with lipophilic prodrugs may be a useful adjunct to cancer chemotherapy.
Sasaki
H
H
Kakutani
T
T
Hashida
M
M
Sezaki
H
H
D000042:Absorption; D000818:Animals; D055598:Chemical Phenomena; D002626:Chemistry, Pharmaceutical; D002627:Chemistry, Physical; D002851:Chromatography, High Pressure Liquid; D004655:Emulsions / Q000032:analysis; D007273:Injections, Intramuscular; D008081:Liposomes / Q000008:administration & dosage*; D008297:Male; D016685:Mitomycin; D008937:Mitomycins / Q000378:metabolism* / Q000627:therapeutic use; D009132:Muscles / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D013997:Time Factors
D004655:Emulsions; D008081:Liposomes; D008937:Mitomycins; D016685:Mitomycin