Apoptosis-Inducing Antitumor Activity of Curcumin-Loaded PCL Microfibers Incorporating Nano-Hydroxyapatite for Breast Cancer Therapy

Breast cancer remains one of the most prevalent and life-threatening cancers worldwide, emphasizing the need for innovative therapeutic strategies that enable localized and sustained drug delivery. In this study, hybrid electrospun fibrous mats composed of poly(ε-caprolactone) (PCL), nanohydroxyapatite (n-HAp), and curcumin (Cur) were successfully fabricated and evaluated for breast cancer treatment. The mats were produced by electrospinning with n-HAp concentrations of 1%, 3%, and 5% (w/w), and a fixed Cur content of 5% (w/w). Morphological analysis revealed uniform, randomly oriented, and bead-free fibers with average diameters of 2.34 ± 0.31 μm, 1.30 ± 0.90 μm, 1.10 ± 0.40 μm, and 1.50 ± 0.90 μm for PCL/Cur, PCL/1HAp-Cur, PCL/3HAp-Cur, and PCL/5HAp-Cur, respectively. FTIR and XRD analyses confirmed the successful incorporation of Cur and n-HAp into the PCL matrix without chemical degradation, while partial amorphization of the additives enhanced their dispersion within the fibers. Contact angle results indicated increased hydrophilicity with higher n-HAp content, reaching the lowest value (112 ± 1.8°) for PCL/3HAp-Cur. In vitro drug release experiments demonstrated a biphasic release behavior, with cumulative Cur release after 24 h of approximately 20%, 30%, 60%, and 80% for PCL/Cur, PCL/1HAp-Cur, PCL/3HAp-Cur, and PCL/5HAp-Cur, respectively. The release kinetics were best fitted to the Weibull model, indicating a diffusion-controlled mechanism. Biological evaluations revealed that PCL/3HAp-Cur exhibited the strongest anticancer activity, reducing MDA-MB-231 breast cancer cell viability to ∼45% after 48 h, while maintaining high biocompatibility with L929 fibroblast cells (>87% viability). Annexin V/PI flow cytometry confirmed apoptosis as the dominant mode of cell death. Overall, the findings demonstrate that PCL/3HAp-Cur nanofibrous mats offer an optimal balance of structural uniformity, sustained Cur release, enhanced hydrophilicity, and selective anticancer efficacy, making them promising candidates for localized breast cancer therapy.