The Study of Polyethyleneglycol-Coated Liposomes Containing CPT-11

Abstract

Polyethyleneglycol (PEG) -coated liposomal CPT-11 (PEG-LCPT(11)) was prepared and its pharmaceutical usefulness was examined. These liposomes, plain liposomal CPT-11 (PLCPT(11)) and PEG-LCPT(11), were composed of dimyristoylphosphatidylcholine, cholesterol, and dimyristoylphosphatidylglycerol (10 : 10 : 6, mol/mol) with or without PEG. The mean particle diameters were both about 1 60 nm. The trapping efficiencies were approximately 90%. In a distribution study, CDFl mice were injected with CPT-11 solution (CPT(11)sol), PLCPT(11) and PEG-LCPT(11) at a dose of 10 mg/kg (i.v.). Concentrations in each tissue of CPT-11 and SN-38, the active metabolite of CPT-11, were determined. After the administration, CPT-11 and SN-38 concentrations in the blood increased by liposomal encapsulation (liposomalization), and the circulation time in the blood was prolonged further by PEG-modification of the liposomes (PEGylation). In the liver, PLCPT(11) was rapidly taken up by the reticuloendothelial system (RES), and the uptake was avoided by PEGylation. Tumor accumulations of CPT-11 and SN-38 were accompanied by an increase in antitumor activity of CPT-11 by liposomalization. Thus, the prolongation of the circulation time in the blood by liposomalization and the avoidance of the RES uptake by PEGylation caused passive targeting of the tumor, with a resulting increase in the antitumor activity of CPT-11.