pH-sensitive polymeric micelles enhance the co-delivery of doxorubicin and docetaxel: an emerging modality for treating breast cancer

Abstract

Designing and preparing a co-delivery system based on polymeric micelles have attracted in recent years. Co-delivery of anti-cancer agents within pH-sensitive polymeric micelles could provide superior advantages over the co-administration of free drugs, since it enables simultaneous delivery of drugs to reach an optimum synergistic dose right to the tumor. DOX was conjugated to the polymer through a hydrazine linker by Schiff’s base reaction. Then, DTX was encapsulated into the core of the polymer to the resulting DOX-Hyd-PM/DTX micelle with optimum molar ratios of 1:1 and 1:5 (DOX/DTX). The final formulations showed the desired particle size and increased release of DOX and DTX in acidic media (pH 5.5). The cytotoxicity assay of DOX-Hyd-PM/DTX indicated the highest synergistic effect on both 4T1 and TUBO cell lines over other formulations. Interestingly, in accordance with in vitro results, DOX-Hyd-PM/DTX revealed a promising anti-tumor activity in mice-bearing 4T1 breast cancer tumor with higher tumor accumulation of DOX and DTX after 24 h compared to free drugs combination. These findings point to the potential use of such smart nanodrug delivery systems in cancer treatment, where the synergistic effect of both drugs may be used to enhance therapeutic response.