In this study, we have investigated the biodistribution and pharmacokinetic analysis of
paclitaxel (PTX) and the apoptotic signaling molecule,
C6-ceramide (CER), when administered in a multifunctional
polymer-blend nanoparticle formulation to female nude mice bearing an orthotopic
drug sensitive MCF7 and multidrug resistant MCF7 TR (MDR-1 positive) human breast
adenocarcinoma. A
polymer-blend nanoparticle system was engineered to incorporate temporally controlled sequential release of the
combination drug payload. Hereby, PTX was encapsulated in the pH-responsive rapid releasing
polymer,
poly(beta-amino ester) (PbAE), while CER was present in the slow releasing
polymer,
poly(D,L-lactide-co-glycolide) (PLGA) within these blend nanoparticles. When particle formulations were administered intravenously to MCF7 and MCF7 TR
tumor bearing mice, higher concentrations of PTX were found in the blood due to longer retention time and an enhanced
tumor accumulation relative to administration of free
drug. In addition, the PLGA/PbAE blend nanoparticles were effective in enhancing the residence time of both drugs at the
tumor site by reducing systemic clearance. Overall, these results are highly encouraging for development of multifunctional
polymer-blend nanoparticle formulations that can be used for temporal-controlled administration of two drugs from a single formulation.