We have studied the antitumor effect of liposome-entrapped cis-bis-N-decyl-iminodiacetato-1,2-diaminocyclohexane-platinum(II)(L-N-decyl-IDP)in mouse models of experimental tumor metastases. the liposomal preparation was compared with the free drug in suspension (F-N-decyl-IDP). In the intraperitoneal (ip) L1210 leukemia model, a single ip injection at the maximum tolerated dose (MTD) of both the free drug and the liposomal drug was equally effective (%T/C 175). However, the free drug was more effective in a triple ip injection schedule at the MTD (%T/C 500 for F-N-decyl-IDP vs. 300 for L-N-decyl-IDP), with twoofsix animals cured by the free drug. In the intravenous (iv) L1210 leukemia model, a single iv injection at the MTD was ineffective for the free drug and only marginally effective for the liposomal preparation (%T/C 112 for F-N-decly-IDP vs. 125 for L-N-decyl-IDP). In a triple iv injection at the MTD, F-N-decyl-IDP was only marginally effective (%T/C 125-128), while L-N-decyl-IDP was clearly superior (%T/C 171-187). In the M5076 mouse reticulosarcoma model, a single injection of L-N-decyl-IDP at the MTD inhibited growth of spleen metastases while the free drug was ineffective. Single MTD injections of either free or liposomal drug were ineffective against liver metastases of the same tumor. In a triple dose schedule, one-half the MTD of L-N-decyl-IDP resulted in a 30% reduction in the number of liver metastases compared with the free drug and elimination of spleen metastases. the triple injection schedule at the MTD of L-N-decyl-IDP inhibited the growth of liver metastases by 95% eliminated spleen metastases, and resulted in the longest survival in the animal groups. F-N-decyl-IDP in the same schedule was ineffective. the results of this study expand and correlate well with our previous findings on the pharmacokinetics and tissue distribution of N-decyl-IDP. the current data show the effect of liposome entrapment on the bioavailability of the drug studied, and the potential of L-N-decyl-IDP for the treatment of hepatosplenic tumor metastases.
ASJC Scopus subject areas
- Pharmaceutical Science