EFFECT OF LIPOSOMALIZATION ON THE ANTITUMOR-ACTIVITY, SIDE-EFFECTS AND TISSUE DISTRIBUTION OF CPT-11

We have examined the efficacy of liposomalization and polyethyleneglyc ol (PEG) modification of liposomes on the antitumor activity, side-eff ects and tissue distribution of irinotecan hydrochloride (CPT-11). PEG -liposome was confirmed to elevate the plasma circulation of CPT-11 an d SN-38 (active metabolite) concentrations. The tumor accumulation of CPT-Il and SN-38 was increased by the PEG-modified liposomes. The anti tumor activity of CPT-11 increased due to the elevated tumor distribut ion of CPT-11 and SN-38 levels by the PEG-modified liposomes. In the t umor, CPT-11 was converted to SN-38. Thus, it is considered that passi ve targeting to the tumor by liposomalization elevated the SN-38 level in the tumor especially and increased the antitumor activity of CPT-1 1. Furthermore, intestinal disorder, a side toxicity of CPT-11, decrea sed dependent on the CPT-11 and SN-38 concentrations in the bile by li posomalization. Although the liposomes induce improved tissue distribu tion of the prodrug, the tissue distribution of active metabolites doe s not always improve. However, CPT-ll-entrapped liposome was useful, a s CPT-11 is converted to SN-38 in the tumor. These results suggested t hat the usefulness of CPT-11 could be extended. (C) 1998 Elsevier Scie nce Ireland Ltd.