pH-responsive chitosan-sodium alginate nanocarriers for curcumin delivery against brain cancer

Curcumin (CUR) exhibits potent anticancer properties and has been widely investigated for the treatment of various malignancies. However, its clinical application is limited by poor aqueous solubility, rapid systemic metabolism, and a short circulation half-life. In the present study, a pH-responsive hybrid nanocarrier system was developed based on sodium alginate (SA), chitosan (CS), and cerium oxide (CeO₂) nanoparticles (NPs), using a water-in-oil-in-water (W/O/W) double emulsion technique. This system was designed to enhance CUR stability, enable controlled and sustained release, and improve pharmacokinetic parameters such as half-life and biodistribution. The resulting nanocarriers exhibited spherical morphology with textured surfaces, a positive surface charge, and nanoscale dimensions. Structural characterization via XRD and FTIR confirmed a quasi-amorphous composite matrix and successful encapsulation of CUR, achieving an encapsulation efficiency of approximately 86 %. Drug release studies conducted at physiological and acidic pH demonstrated a sustained, pH-dependent release profile, well-fitted by the Baker-Lonsdale kinetic model. Cytotoxicity assays using U-87MG2 glioma and healthy astrocyte cell lines indicated that the CUR-loaded nanocarriers selectively induced tumor cell death while exhibiting minimal toxicity toward normal cells. Moreover, the inclusion of CeO₂ NPs was found to mitigate CUR degradation under physiological conditions, thereby contributing to its enhanced therapeutic performance. Flow cytometry analysis further revealed a significant induction of apoptosis in glioma cells treated with the CUR-loaded nanocomposites. Collectively, these findings underscore the potential of the developed CS/SA/CeO₂@CUR nanoplatform as an effective and biocompatible strategy for brain cancer therapy.