Co-encapsulation of anti-breast cancer drugs in nanoparticles reduce antagonism

Abstract

The totality of tumour treatment dictated therapy outcome and the probability of cancer remission. Differential metabolism of docetaxel (DCL) and tamoxifen (TAM), which resulted in drug antagonistic effects were shown to suppress treatment efficacy in subpopulation of cancer cells. However the potential of nanoparticles, which spatially protected both drugs from metabolizing enzymes to reduce this antagonism, remained unknown. We demonstrated that after the co-delivery of DCL and TAM in poly (lactide)-D-a-tocopheryl polyethylene glycol succinate nanoparticles (PLA-TPGS NPs), drug antagonism was significantly reduced versus its free unprotected form, and this effect attenuated at high drug concentrations. The fluorescent model drug coumarin 6 encapsulated in nanoparticles, exhibited enhanced cellular uptake over its free counterpart, and surprisingly, at correspondingly low drug concentrations. Thus our data suggested that reducing drug antagonism was correlated to the cellular uptake of nanoparticles, resulting from the spatial protection of both drugs until released intracellular for therapeutic anti-cancer effect.