Nanoparticle delivery of chemotherapy combination regimen improves the therapeutic efficacy in mouse models of lung cancer

Combinations of cisplatin and docetaxel are effective against many cancers. However, combination chemotherapy can lead to increases in toxicity and imprecise exposure of target cells to a specific drug ratio leading to treatment resistance. Co-encapsulation within nanoparticles has shown clinical success with other chemotherapies in overcoming these complications. Therefore, we developed co-formulations of cisplatin and docetaxel in PLGA-PEG nanoparticles using cisplatin prodrugs for efficient encapsulation. The combination nanoparticles show significant improvements in the therapeutic index versus the free drugs in vitro and against murine lung cancer models. Cisplatin prodrug structure also dictated therapeutic efficacy likely due to differences in co-formulation properties.161