Abstract pH-sensitive nanoparticles offer a promising strategy to improve therapeutic outcomes while minimizing systemic toxicity. In this study, poly(2-(diethylamino)ethyl acrylamide)-grafted chitosan (CHS-g-PDEAEAm) copolymers with various compositions were synthesized via a microwave-induced method and developed as pH-responsive nanocarriers for erlotinib (ET), a hydrophobic anticancer drug. The successful grafting of PDEAEAm onto the CHS backbone was confirmed by FTIR, 1 H-NMR, and 13 C-NMR analyses. Subsequently, ET-loaded CHS-g-PDEAEAm nanoparticles (NPs) were fabricated, and their physicochemical properties, both ET-loaded and unloaded, were systematically characterized using TEM/FE-SEM, DLS, FTIR, XRD, BET, TGA, and DSC analyses. The obtained NPs exhibited high ET entrapment efficiency, satisfactory stability, and a sustained, pH-dependent drug release profile, with slower release at physiological pH and accelerated release under acidic conditions. Furthermore, ET release was influenced by the grafting percentage, and CHS-g-PDEAEAm@ET NPs displayed a slower ET release compared to CHS@ET NPs. ET release from most NPs followed Higuchi-type diffusion-controlled kinetics. In vitro cytotoxicity studies revealed good biocompatibility of CHS-g-PDEAEAm NPs toward L-929 fibroblast cells (86.89% cell viability at 200 μg/mL), while ET-loaded NPs demonstrated pronounced anticancer activity against A-549 lung cancer cells (6.24% cell viability at 200 μg/mL). Overall, the CHS-g-PDEAEAm NPs demonstrated favorable colloidal stability, pH-sensitivity, sustained drug release, good biocompatibility with low hemolytic activity, and promising anticancer activity, suggesting their potential applicability as nanocarriers for hydrophobic anticancer drugs. Graphical abstract
Karaçoban et al. (2026) studied this question.