Positively charged liposomes containing tumor necrosis factor in solid tumors.
The antitumor effects against solid tumors, such as Meth A sarcoma, MH-134 hepatoma and colon 26 adenocarcinoma, were examined after intratumoral administration of liposomes and Tumor Necrosis Factor (TNF) solution. The antitumor effects of liposomes against solid tumors were superior to those of TNF solution. In particular, the antitumor effect of positively charged (decyl amine) liposomes was superior to that of negatively charged liposomes and TNF solution. Further, positively charged liposomes containing a higher dose of TNF than the solution could be administered without killing the mice, because of reduced side-effects. After intratumoral (Meth A sarcoma) administration, the TNF plasma concentration was determined in order to estimate the systemic side-effects of TNF. The area under curve (AUC) after administration of positively charged liposomes containing 6 times dose of TNF was about 1/30 the AUC after the administration of TNF solution. After administration of positively charged liposomes, TNF was mainly retained locally. Positively charged liposomes exhibited a stronger antitumor effect than the solution and had a lower AUC (about 1/180) than the solution. Consequently, some solid tumors could be completely cured by positively charged liposomes, because of their increased antitumor effect and reduced toxicity.
Yasui
K
K
Department of Formulation Research, Pharmaceutical Research of Dainippon Pharmaceutical Co. Ltd., Fukushimaku, Osaka, Japan.
Nakamura
Y
Y
D000818:Animals; D004305:Dose-Response Relationship, Drug; D004337:Drug Carriers; D005260:Female; D015552:Injections, Intralesional; D008081:Liposomes; D051379:Mice; D008809:Mice, Inbred C3H; D009374:Neoplasms, Experimental / Q000188:drug therapy*; D014409:Tumor Necrosis Factor-alpha / Q000008:administration & dosage* / Q000627:therapeutic use
D004337:Drug Carriers; D008081:Liposomes; D014409:Tumor Necrosis Factor-alpha