Hyaluronic acid-coated capecitabine nanostructures for CD44 receptor-mediated targeting in breast cancer therapy†

Hyaluronic acid-coated capecitabine-loaded nanomicelles (HA-CAP-M) are synthesized to overcome the challenges associated with capecitabine (CAP) conventional delivery such as low permeability and systemic toxicity. Nanomicelles containing saponin, glycerol, and vitamin-E TPGS formulation of capecitabine were further encapsulated with hyaluronic acid (HA) for CD44 receptor-mediated targeting. Optimization of the formulation was carried out using a Box–Behnken design resulting in 17.8 nm particle size, 89.3% entrapment efficiency and a biphasic drug release profile. Characterization studies validated stability, spherical structure, and desirable encapsulation characteristics of the nanomicelles. Lowered critical micelle concentration (CMC) and acceptable drug release kinetics revealed improved thermodynamic stability and controlled drug release, as predicted by the Hixson–Crowell model. HA-CAP-M showed much higher permeability and cytotoxicity than the free CAP, with an IC₅₀ of 2.964 μg mL⁻¹ in in vitro experiments. AO/PI staining also demonstrated dose-dependent apoptosis in MCF-7 breast cancer cells and validated the highly effective active targeting of HA. In addition, the formulation demonstrated good stability during storage and dilution conditions, confirming its stability as a drug delivery platform. In conclusion, HA-functionalized nanomicelles provide a biocompatible and efficient system for the targeted breast cancer therapy, enhancing the therapeutic efficacy of capecitabine.