Magnetic casein-CaFe2O4 nanohybrid carrier conjugated with progesterone for enhanced cytotoxicity of citrus peel derived hesperidin drug towards breast and ovarian cancer.

A novel progesterone-receptor targeted nanohybrid carrier based delivery of hesperidin was investigated in the present work. Casein‑calcium ferrite nanohybrid carrier was synthesized using desolvation followed by ionic-gelation. The citrus peel extracted hesperidin drug (CHD) was encapsulated in the carrier via pH based coacervation, after which the targeting ligand progesterone was conjugated through activate ester procedure. The carrier formulation was characterized using techniques like XRD, FTIR, SEM, VSM and DLS. The bioactive components in CHD were analyzed using HPLC. Taguchi optimization gave a maximum of 89.54% hesperidin encapsulation in the carrier. Incorporation of superparamagnetic calcium ferrite nanoparticles resulted in improved drug encapsulation and magnetic induced drug delivery. The carrier exhibited a stimuli-responsive drug release behavior, with good stability at physiological pH (7.4) and a higher release under acidic pH (5.4 and 1.2) favoring anticancer applications. The drug release followed Fickian diffusion mechanism as predicted by different kinetic models. Cell viability assay on L929 fibroblast cells verified the biocompatibility of the formulation. The specific recognition and targeted chemotherapy rendered by the progesterone-conjugated carrier enhanced the cytotoxicity of CHD against SKOV-3 ovarian and MDA-MB-231 breast cancer cells, resulting in a significant 30-fold reduction in the (Half-maximal inhibitory concentration) IC₅₀ values.