Synthesis, characterization, and in vitro drug release evaluation of AHMA-PEG nanoparticles loaded with teriflunomide

Polymeric nanoparticles are promising drug delivery systems for improving solubility, sustaining release, and reducing systemic toxicity. In this study, AHMA-PEG nanoparticles were developed as carriers for teriflunomide, a poorly water-soluble immunomodulatory drug used in multiple sclerosis. Nanoparticles were prepared by free-radical emulsion polymerization of 3-(acryloyl)-2-hydroxypropyl methacrylate (AHMA) in the presence of polyethylene glycol (PEG 1500), followed by post-synthesis drug loading. Formulation conditions were systematically optimized by varying surfactant concentration, reaction temperature, and polymerization time. The optimized formulation (50 mg SDS, 90 °C, 2 h) produced nanoparticles with mean hydrodynamic diameter 255.1 ± 8.2 nm, Z-average 280.6 ± 13.0 nm, PDI 0.277 ± 0.025, and zeta potential -30.7 ± 0.7 mV. SEM revealed spherical primary particles (20-60 nm) arranged in porous interconnected structures. FTIR, UV-vis, and NMR analyses confirmed polymer formation, PEG incorporation, and successful teriflunomide loading. Encapsulation efficiency and loading capacity were 83.7% and 14.34%, respectively. Thermal analyses showed a semi-crystalline polymeric system with adequate stability for pharmaceutical handling. In vitro release studies demonstrated pH-dependent sustained release kinetics, with modestly faster and more complete release under acidic conditions (93.47 ± 2.28% at pH 5.5, 120 h) compared with physiological pH (87.33 ± 1.74% at pH 7.4, 120 h), corresponding to a 6.1 percentage-point differential in final cumulative release. A 1.68-fold acceleration of early-phase release rate under acidic conditions and a pH-dependent shift in the Korsmeyer-Peppas exponent (n = 0.538 at pH 7.4 versus n = 0.665 at pH 5.5) together confirm that the AHMA-PEG matrix exhibits pH-modulated release kinetics consistent with enhanced endosomal drug liberation at acidic intracellular pH, even though the overall cumulative release differential is modest compared with covalently pH-cleavable systems. Release data were best described by the Higuchi model at pH 5.5, while Higuchi and Hixson-Crowell showed near-equivalent fits at pH 7.4. Korsmeyer-Peppas analysis indicated anomalous non-Fickian transport under both conditions. These findings support AHMA-PEG nanoparticles as a promising carrier platform for sustained teriflunomide delivery and justify further biological evaluation.