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

• PEGDA–cystamine hydrogels were synthesized via aza-Michael addition. • The hydrogel network exhibits redox- and pH-responsive degradation behavior. • Curcumin was efficiently loaded within the hydrogel matrix. • The 1:2 (PEGDA:cystamine) ratio optimized drug release and cytotoxicity. • Ammonium salt formation enhances hydrogel stability under acidic conditions. 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. 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. 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. PEGDA–cystamine hydrogels exhibit redox- and pH-responsive behavior, enabling controlled curcumin release and enhancing its bioactivities through an optimally crosslinked PBAE network.