Paclitaxel and Ceramide Combination Therapy in Biodegradable Polymeric Nanoparticles to Overcome Multidrug Resistance in Cancer

摘要

Multidrug resistance (MDR) is a common attribute of cancer chemotherapy resulting in poor clinical prognosis. In this study, we have examined the potential of exogenous C_6-ceramide (CER), administration in augmenting the therapeutic efficacy of paclitaxel (PTX) in MDR tumor model. In order to enhance tumor-targeted and intracellular delivery, PTX and CER were administered in poly(ethylene oxide)-modified poly(epsilon-caprolactone) nanoparticles. In vivo therapeutic efficacy and safety studies were performed in subcutaneous sensitive (wild-type) and MDR-1 positive SKOV-3 human ovarian adenocarcinoma xenografts in female nuu mice. The results of this study show that combination of PTX and CER in biodegradable polymeric nanoparticles can serve as a very effective therapeutic strategy to overcome MDR in solid tumors.