Functionalized Colloidal Hydroxyapatite for Combined Delivery of Cannabidiol and Epirubicin: Characterization, Biomimetic Membrane Interaction, and Cytotoxicity Studies

Abstract

Introduction A stable colloidal hydroxyapatite (cHAp) platform was successfully developed for the co-delivery of cannabidiol (CBD), a natural bioactive compound, and epirubicin (EPI), a chemotherapeutic agent, to enhance cytotoxicity against ovarian cancer cells. Methods Colloidal cHAp was synthesized and functionalized with CBD and EPI to obtain a multifunctional drug delivery system. The resulting composite was characterized using high-performance liquid chromatography, UV–Vis spectrometry, transmission and scanning electron microscopies, Fourier-transform infrared spectroscopy, Turbiscan analysis, and differential scanning calorimetry. Drug release in phosphate-buffered saline (PBS, pH 7) was evaluated by differential pulse voltammetry. Interactions with model lipid monolayers mimicking healthy and cancerous cell membranes were investigated using the Langmuir technique, and cytotoxicity was assessed by MTS assays. Results The successful incorporation of both biologically active compounds into the cHAp carrier and its excellent colloidal stability were confirmed. The epirubicin loading content was 0.0605 mg per 1 mg of cHAp. Drug release followed a time-dependent profile, reaching approximately 2 μg mL−1 after 24 h. The functionalized cHAp systems exhibited enhanced affinity toward model lipid monolayers and significantly reduced the viability of ovarian cancer cells compared with the free drug and non-functionalized carrier. Conclusion The developed cHAp platform provides a stable and multifunctional carrier for the co-delivery of CBD and epirubicin. Its favorable physicochemical properties, enhanced membrane interactions, and improved anticancer activity highlight its potential as a promising nanocarrier for targeted ovarian cancer therapy.