Hyaluronic Acid Nanocapsules as pH-Responsive Nanocarriers for Controlled Doxorubicin Delivery

Despite the progress in drug delivery applications, fabricating an effective nanocarrier platform still poses a significant challenge in optimizing controlled release mechanisms and enhancing therapeutic efficacy. In this study, hyaluronic acid nanocapsules (HANCs) were synthesized by using a polyaddition reaction in the inverse miniemulsion technique. The formulation was optimized for doxorubicin (DOX) encapsulation. Both physicochemical and morphological characterizations of the varied nanocapsule formulations were performed. The hollow capsule morphology of the produced nanoparticles was clearly observed via transmission electron microscopy. Furthermore, stability monitoring was carried out on the selected formulation, which remained stable for over 100 days. DOX encapsulation was successfully achieved, and the drug release mechanisms were investigated at pH 6.5 and 7.4 to mimic the tumor and healthy tissue microenvironment. A significantly higher release of DOX was obtained at pH 6.5, whereas drug leakage at pH 7.4 was considerably limited as intended. In addition, the cytotoxicity and anticancer activity of DOX-loaded and DOX-free HANCs were analyzed by cell viability tests on L929 mouse fibroblast cells and MCF-7 breast cancer cells. DOX-loaded HANCs induced higher cytotoxicity in cancer (MCF-7) cells compared to healthy (L929) cells, with the most pronounced difference observed after 72 h of cell interaction. The findings demonstrate that the developed HANCs offer a practical platform for pH-sensitive drug delivery applications with inherent potential for targeted cancer therapy.