Unlocking biomedical potential of eco-friendly polyhydroxyurethane hydrogel: controlled release of cefadroxil antibiotic.

Polyurethane (PU) hydrogels have been conventionally synthesized using the polyaddition of toxic polyisocyanates with polyols in organic solvents or in bulk, then swelling them in water. In this research work, a previously reported fructose-derived polyhydroxyurethane /poly(sodium acrylate) hydrogel synthesized through a catalyst-free non-isocyanate aqueous route was investigated as a smart pH-responsive platform for the delivery of cefadroxil, a broad-spectrum cephalosporin antibiotic. The novelty of this work lies in the first evaluation of the multifunctional application of a biobased PHU hydrogel for controlled antibiotic delivery, extending its previously reported environmental application to the biomedical domain. The hydrogel exhibited pronounced pH-responsive swelling behaviour, reaching 524.5% swelling at pH 7.4 compared to 54.6% at pH 1.2 after 24 h. Cefadroxil encapsulation efficiency was determined to be 63.7%. Drug release was significantly enhanced at pH 7.4 due to increased ionization of carboxylate groups within the hydrogel network, resulting in increased electrostatic repulsion, network expansion, and accelerated diffusion of the drug. Structural characterisation by FTIR, PXRD, SEM, and TGA confirmed successful hydrogel formation and drug incorporation. Cytocompatibility studies using L929 fibroplast cells demonstrated the non-toxic nature of the hydrogel. The controlled drug release behavior of drug loaded hydrogel followed the Fickian mechanism of diffusion (R2 = 0.9909 at pH 7.4) as suggested by the Korsmeyer-Peppas model. These findings underscore the potential of PHU hydrogels as effective, biocompatible materials for controlled, pH-sensitive drug delivery, contributing to safer and more efficient biomedical applications.