抄録
An antitumor agent irinotecan (CPT-11) is a water soluble derivative of camptothecin. It is a prodrug, and mainly metabolited to an active metabolite (SN-38) in the liver. Even if a prodrug accumulates in a target tissue, namely tumor, by liposomalization, it doesn't necessarily resulted in the increase of antitumor activity. We found that CPT-11 was clearly converted into SN-38 in the tumor in vitro, and tried liposomalization of CPT-11. The mean particle diameters of plain liposomal CPT-11 (PLCPT(11)) and polyethyleneglycol (PEG)-coated PLCPT(11) (PEG-LCPT (11)) were both about 160 nm. The trapping efficiencies were approximately 90%. After the administration of these liposomes to mice, CPT-11 and SN-38 concentrations in the blood increased by liposomalization, and the circulation time in the blood was prolonged further by PEG-modification of the liposomes (PEGylation). In the tumor, CPT-11 and SN-38 concentrations increased by liposomalization. Thus, it is considered that the prolongation of circulation time in the blood by PEGylation caused passive targeting to the tumor. We have expected an increase in the antitumor activity of CPT-11 from the change of the distribution by liposomalization and PEGylation. Because CPT-11 accumulates in the tumor by liposomalization and is converted to the active metabolite in the tumor, we have been anticipating a increase of usefulness by liposomalization of prodrug.
