Injectable PEG-based poly(β-amino ester) hydrogels with tunable biodegradability for stimuli-responsive curcumin delivery

Background Poly(β-amino esters) are biodegradable and chemically versatile polymers synthesized via aza-Michael addition of diverse monomers. Their tunable and stimuli-responsive networks make them promising materials for drug delivery. This study aimed to develop redox- and pH-responsive PEGDA–cystamine PBAE hydrogels for curcumin encapsulation and biomedical applications. Methods Hydrogels were synthesized under alkaline conditions by varying the molar ratios of poly(ethylene glycol) diacrylate (PEGDA) and cystamine. The prepolymers rapidly formed gels at 37 °C. The hydrogels were characterized using FT-IR, 13 C CP-MAS NMR, TGA, and SEM. Biodegradation, drug release, antioxidant, antibacterial, and cytotoxicity assays were conducted to evaluate physicochemical and biological performance. Significant Findings The hydrogels exhibited notable biodegradability and pH-dependent release, with faster curcumin release at higher pH. Curcumin-loaded hydrogels showed approximately double the antioxidant activity of unloaded gels and a lower IC 50 (1.074 mg mL⁻¹ vs. 2.210 mg mL⁻¹). They demonstrated antibacterial activity against Gram-negative (E. coli, P. aeruginosa) and Gram-positive (S. aureus, B. subtilis) strains, with minimum inhibitory concentrations of 27–49 mg mL⁻¹. Although curcumin incorporation did not markedly increase cytotoxicity (IC 50 = 0.535 mg mL⁻¹), the hydrogels maintained biocompatibility and preserved curcumin’s bioactivity. The tunable composition and dynamic covalent chemistry suggest potential for injectable, stimuli-responsive drug delivery systems.