Two Drug Combination Anti-cancer Therapy Based on Topotecan and Vincristine Co-Remote-Loaded into PEGylated Nanoliposomes

In vitro cytotoxicity analysis showed ratio dependant synergism between the chemotherapeutics topotecan (TPT) and vincristine (VCR) against cancer cells. Individual agents in a anticancer drug combination will distribute and be eliminated independently of each other after administration in vivo. This is important if the degree of synergy depends on the ratio of the combined drugs. We decided to use liposomes in order to deliver both drugs simultaneously to the tumor tissue. Analysis of the drug’s physiochemical properties demonstrated that they are good candidates for remote loading. Evaluation of the loading efficiency in different loading conditions showed that the optimal loading conditions of both drugs are similar. We encapsulated both drugs in sterically stabilized nano liposomes (nSSL). Our formulations showed good storage stability and capability to release the drugs in physiological conditions. Liposomal formulations loaded with one drug achieved higher therapeutic efficacy in vivo than the free drugs, and liposomes with two co-encapsulated drugs were more efficacious than liposomes with one drug.

We have demonstrated that drug combinations can be optimized preclinically through pharmacokinetic control by remote loading into nSSL, we provide a new direction by which anticancer treatment should be developed.