title: Effect of liposomalization on the antitumor activity, side-effects and tissue distribution of CPT-11.
abstract: We have examined the efficacy of liposomalization and polyethyleneglycol (PEG) modification of liposomes on the antitumor activity, side-effects and tissue distribution of irinotecan hydrochloride (CPT-11). PEG-liposome was confirmed to elevate the plasma circulation of CPT-11 and SN-38 (active metabolite) concentrations. The tumor accumulation of CPT-11 and SN-38 was increased by the PEG-modified liposomes. The antitumor activity of CPT-11 increased due to the elevated tumor distribution of CPT-11 and SN-38 levels by the PEG-modified liposomes. In the tumor, CPT-11 was converted to SN-38. Thus, it is considered that passive targeting to the tumor by liposomalization elevated the SN-38 level in the tumor especially and increased the antitumor activity of CPT-11. Furthermore, intestinal disorder, a side toxicity of CPT-11, decreased dependent on the CPT-11 and SN-38 concentrations in the bile by liposomalization. Although the liposomes induce improved tissue distribution of the prodrug, the tissue distribution of active metabolites does not always improve. However, CPT-11-entrapped liposome was useful, as CPT-11 is converted to SN-38 in the tumor. These results suggested that the usefulness of CPT-11 could be extended.
authors.affiliation: School of Pharmaceutical Sciences, University of Shizuoka, Yada, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Sadzuka
authors.forename: S
authors.initials: S
authors.lastname: Hirotsu
authors.forename: S
authors.initials: S
authors.lastname: Hirota
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage* / Q000378:metabolism / Q000494:pharmacology; D001646:Bile / Q000737:chemistry; D001835:Body Weight / Q000187:drug effects; D002166:Camptothecin / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000032:analysis / Q000378:metabolism / Q000494:pharmacology; D002286:Carcinoma, Ehrlich Tumor / Q000378:metabolism; D004337:Drug Carriers; D005243:Feces / Q000737:chemistry; D000077146:Irinotecan; D008081:Liposomes; D008099:Liver / Q000737:chemistry; D008297:Male; D051379:Mice; D009368:Neoplasm Transplantation; D014867:Water / Q000032:analysis
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D004337:Drug Carriers; D008081:Liposomes; D014867:Water; D000077146:Irinotecan; D002166:Camptothecin