Fabrication of curcumin-loaded nano-micelles based on quercetin-quarternary ammonium-chitosan (Qu-QCS) conjugate and evaluation of synergistic effect with doxorubicin against breast cancer

Abstract

The applications of quarternized chitosans have achieved notable success in the development of drug-delivery systems. This study reported the preparation of quercetin-quarternized chitosan (Qu-QCS) conjugate and its application for the fabrication of stable and safe curcumin (cur) loaded nano-micelles with high targeting ability and selectivity towards the breast cancer cell lines. Moreover, doxorubicin (dox) was co-treated with the nanomicelles to enhance the efficacy and reduce the cardiotoxic effects of dox. Structural properties of Qu-QCS were evaluated by FTIR, DSC, and XRD analysis and the yield obtained was 48.82 %. The nano-micelles obtained showed spherical shape, <200 nm size, 48.38 % entrapment efficiency, prolonged stability at 4 °C and pH-responsive release pattern. The cur-loaded nano-micelles showed higher activity and selectivity against breast cancer (MCF-7 and MDA-MB-231) cell lines with enhanced internalization, lower toxicity to the normal cardiomyoctyes (H9C2), enhanced the cell cycle arrest at the G2/M phase of the breast cancer cell lines and induced apoptosis with high intensity compared to pure cur. Moreover, the co-treatment of dox with cur-loaded Qu-QCS nano-micelles showed increased anticancer activity and reduced cardiotoxicity. Overall, this study suggests the potential applications of cur-loaded Qu-QCS micelles in the delivery of chemotherapeutic agents and complementary support in combination with chemotherapeutic agents.