Inhibition of pulmonary metastasis in mice by all-trans retinoic acid incorporated in cationic liposomes.
The purpose of this study was to investigate whether all-trans retinoic acid (ATRA), an active metabolite of retinal, incorporated in cationic liposomes composed of 1,2 dioleoyl-3-trimethylammonium propane (DOTAP)/cholesterol could inhibit established metastatic lung tumors by delivery to the pulmonary tumor site after intravenous injection. After intravenous injection in mice, the highest lung accumulation of [(3)H]ATRA was observed by the DOTAP/cholesterol liposomes formulation, while other formulations including [(3)H]ATRA dissolved in serum or [(3)H]ATRA incorporated in distearoyl-l-phosphatidylcholine (DSPC)/cholesterol liposomes produced little accumulation in the lung. In mice used as a model of lung cancer metastasis, ATRA incorporated in DOTAP/cholesterol liposomes, injected intravenously, reduced the number of tumor nodules compared with free ATRA or ATRA incorporated in DSPC/cholesterol liposomes. These results suggest that ATRA incorporated in cationic liposomes would be an effective strategy for differentiation therapy of lung cancer metastasis.
Suzuki
Sachiko
S
Department of Drug Delivery Research, Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, Kyoto 606-8501, Japan.
Kawakami
Shigeru
S
Chansri
Narin
N
Yamashita
Fumiyoshi
F
Hashida
Mitsuru
M
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000494:pharmacology* / Q000633:toxicity; D002412:Cations; D045744:Cell Line, Tumor; D017690:Cell Transplantation; D055598:Chemical Phenomena; D056486:Chemical and Drug Induced Liver Injury / Q000473:pathology; D002627:Chemistry, Physical; D003110:Colonic Neoplasms / Q000188:drug therapy / Q000473:pathology; D004337:Drug Carriers; D005229:Fatty Acids, Monounsaturated; D007275:Injections, Intravenous; D008081:Liposomes; D008168:Lung / Q000473:pathology; D008175:Lung Neoplasms / Q000517:prevention & control* / Q000556:secondary*; D008297:Male; D051379:Mice; D009368:Neoplasm Transplantation; D000644:Quaternary Ammonium Compounds; D051381:Rats; D011916:Rats, Inbred F344; D012995:Solubility; D014018:Tissue Distribution; D014212:Tretinoin / Q000008:administration & dosage* / Q000494:pharmacology* / Q000633:toxicity
D000970:Antineoplastic Agents; D002412:Cations; D004337:Drug Carriers; D005229:Fatty Acids, Monounsaturated; D008081:Liposomes; D000644:Quaternary Ammonium Compounds; D014212:Tretinoin; C070046:1,2-dioleoyloxy-3-(trimethylammonium)propane