pH sensitive polyelectrolyte complex micelles for highly effective combination chemotherapy

Abstract

The co-encapsulation of two or more drugs in the same carrier affords synergistic therapeutic effects and enhanced therapeutic potency. For this, polyethylene oxide-b-polyacrylic acid di-block polymer based-smart pH-sensitive di-block polyelectrolyte complex (PEC) micelles were designed to encapsulate mitoxantrone (MTX) and doxorubicin (DOX) with high payload capacity and precise drug ratio. Three molar ratios (MTX/DOX: 2 : 1, 1 : 1, 1 : 2) of the drug-loaded PECs were prepared with high payload capacity and evaluated for various physicochemical characteristics. The dual drug combination exhibited a synergistic cytotoxic activity against both sensitive (MCF-7 and A-549) and resistant cancer cell lines (MDA-MB-231), unlike the individual drugs. Dual drug-loaded nanosystems (MTX/DOX-M) prolonged the blood circulation of drugs, and a synergic ratio was maintained throughout the study period. MTX/DOX-M exhibited superior therapeutic efficacy in xenograft models; by contrast, the free drug cocktail caused a significant loss of body weight in mice. Taken together, our results suggest that PEC micelles have great potential as nano-scaled therapeutic delivery systems for combination chemotherapy.