RESUMO
The simultaneous administration of dipalmitoylphosphatidylcholine liposomes and methyl-bis(beta-chloroethyl)amine (HN2) to Ehrlich ascites tumor-bearing mice results in prolongation of survival, reduction of toxicity, and increase in chemotherapeutic index when compared to HN2 alone. Delay for as little as 10 min in the administration of HN2 following the liposomes eliminates this enhancement of activity and, in fact, abolishes much of the chemotherapeutic activity of the alkylating agent itself. The enhancement phase of liposomal action correlates with a significant increase in HN2 uptake by tumor cells which cannot be due to entrapment of drug in the liposomes, while the reduced toxicity could reflect subsequent HN2 transport. Persistent membrane alteration is also seen in the contrasting case of the lipid-soluble alkylating agent 1,3-bis(2-chloroethyl)-1-nitrosourea where advanced administration of the liposome preparation significantly increases the chemotherapeutic activity. The observed effects are also shown to be influenced by liposome composition. The hypothesis is advanced that, under the given experimental conditions, liposomes can cause persistent reorganization of cell membranes which follow a characteristic course and have specific features.
