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Abstract This research presents an innovative β‐cyclodextrin/polyacrylic acid/hydroxyapatite (Cyc/PAA/HAP) nanocarrier engineered for pH‐responsive administration of 5‐fluorouracil (5‐FU) in liver cancer therapy. The nanocarrier exhibited enhanced drug‐loading efficacy, achieving an entrapment efficiency of 86.5% and a drug‐loading capacity of 47.75%. It also exhibited enhanced physicochemical properties with an average hydrodynamic size of 171.25 nm and a high reactive negative zeta potential of −38.64 mV, thus exhibiting colloidal stability. The nanotechnology demonstrated efficient pH‐responsive activity, releasing 110% of the encapsulated drug at the acidic pH in tumor microenvironments (pH 5.4), as opposed to releasing 70% at physiological pH (7.4) after 96 h. In vitro cytotoxicity tests showed selective cytotoxicity, reducing the viability of HepG2 liver cancer cells by 40% and preserving over 85% vitality in normal L929 cells. These results address significant issues in traditional 5‐FU treatment—i.e., low bioavailability, systemic toxicity, and lack of tumor specificity—by presenting a biocompatible, targeted drug delivery platform. The synergistic effect of Cyc, PAA, and HAP highlights the system's vast potential for clinical application toward treating liver cancer and potentially other.
Pourmadadi et al. (Tue,) studied this question.