Novel Dual Drug-Loaded Block Ionomer Complex Micelles for Enhancing the Efficacy of Chemotherapy Treatments

Abstract

Combination of two or more drugs has emerged as a promising strategy to elicit synergistic therapeutic responses that can overcome multidrug resistance of cancer cells at various stages of the growth cycle. In the current study, we investigated the efficacy of two drugs, mitoxantrone (MTX) and doxorubicin (DOX), co-encapsulated in a polyethylene oxide-b-polyacrylic acid polymer. The resulting block ionomer complex (BIC)-based combination chemotherapy provides a novel method for enhancing the therapeutic efficacy of chemotherapies. The BIC micelles were very stable at physiological pH, and showed a temporally sequenced release profile for the co-encapsulated drugs at tumor pH. This suggests that the micelles can deliver chemotherapeutic agents at the appropriate cellular stage. At a predetermined and carefully controlled ratio (MTX: DOX=2:1), the two drugs worked synergistically within A549 small lung cancer cells. Taken together, these findings suggest that the synergistic activity of ratiometrically controlled drug combinations can enhance their chemotherapeutic action and overall therapeutic index.