Doxorubicin and Curcumin-Loaded Nanomicelles Targeting Multidrug Resistance in Cancer

Multidrug resistance (MDR) poses a significant challenge in cancer therapeutics, particularly in breast cancer treatment. This study emphasizes the importance of addressing MDR through a synergistic combination of doxorubicin (DOX) and curcumin (CUR) delivered using a novel nanocarrier, quaternary ammonium palmitoyl glycol chitosan (GCPQ). GCPQ is a self-assembling polymer, making it an ideal nanocarrier for delivering both hydrophilic DOX and hydrophobic CUR. The formulation, termed DCG, demonstrated successful encapsulation of both drugs with sustained release profiles. Characterization studies confirmed the stability, particle size (187 ± 1.36 nm), and zeta potential (− 28 ± 0.48 mV) of the nanoformulation. In vitro studies revealed efficient cellular uptake (P < 0.0001), low hemolytic activity, and enhanced cytotoxicity (88%) in CAL-51 breast cancer cells in comparison to the free drugs (P < 0.05). The DCG nanomicelles induced apoptosis in breast cancer cells, with a remarkable 93% apoptotic effect (P < 0.05) being observed. The in vivo biodistribution investigations demonstrated the safety and efficacy of nanomicelles in normal 6–9-week-old Balb/c mice as well as the DCG nanomicelles capacity to target tumors. This study establishes the promise of the DCG nanoformulation in overcoming MDR in breast cancer, with an IC₅₀ of 80.10 µg/ml and stable storage for up to 3 months. Continued research and clinical trials will be essential to validate the translational potential of the DCG nanoformulation, paving the way for personalized and more effective breast cancer therapies.