Development and evaluation of docetaxel-hesperidin loaded nanoformulation for the treatment of breast cancer

Breast cancer remains a leading cause of cancer-related mortality worldwide. Conventional chemotherapy is often limited by dose-limiting toxicity and the development of drug resistance. Co-delivery of a chemotherapeutic agent with a bioactive natural compound using nanotechnology offers a promising strategy to enhance anticancer activity, improve therapeutic outcomes, and reduce adverse effects. A nanoparticle-based nanoformulation co-loaded with DTX and HES was developed and optimized using a Box–Behnken statistical design. Critical formulation variables were systematically evaluated to obtain optimized particle size, high entrapment efficiency, and desirable drug release behavior. The optimized formulation was characterized for particle size distribution, drug encapsulation efficiency, and in vitro drug release. In vitro cytotoxicity studies were conducted on breast cancer cell lines to assess anticancer efficacy and potential synergism. The optimized DTX–HES nanoparticle exhibited a uniform nanoscale particle size of approximately 108 nm and high entrapment efficiency exceeding 90%. Sustained drug release was observed over 48 hours, indicating effective controlled-release behavior. In vitro cytotoxicity studies showed notable anticancer activity of the co-loaded nanoparticles compared to formulations containing individual drugs, indicating improved therapeutic performance of the combined DTX and HES system. The DTX–HES co-loaded nanoparticle represents a promising nanomedicine-based approach for breast cancer management. By combining dual drug action with controlled delivery, the formulation has the potential to improve therapeutic efficacy, reduce systemic toxicity, and overcome limitations associated with conventional chemotherapy.