Green Synthesis of Smart Hydrogels via Radiation Crosslinking of Sodium Alginate and Citric Acid for pH-Sensitive Doxycycline Hyclate Release

Abstract

Doxycycline hyclate (DH) is a second-generation tetracycline antibiotic with lower toxicity than its predecessors, used for bacterial infections and topically for mucosal and diabetic ulcers. Healthy skin's pH is mildly acidic (4.0-6.0), regulating bacterial flora and preventing infections. Wounds disrupt this pH, revealing the tissue's neutral pH of 7.4, necessitating pH-sensitive controlled drug release for effective chronic wound treatment. This study explores polysaccharide-based hydrogels synthesized by crosslinking sodium alginate/citric acid (NaAlg/CA) solutions using gamma radiation with varying citric acid concentrations for pH-sensitive DH release. The citric acid-modified polysaccharide hydrogels were created using a green method, free of additional chemicals. Citric acid significantly influenced swelling, critical for drug loading and release, with the highest swelling capacity (3500% mass) observed at a 5:1 NaAlg/CA ratio. Hydrogels were tested for pH-dependent swelling and DH drug release profiles at pH 5.5, 7.4, and 9.0. The results indicate that at pH 7.4, which replicates the pH of chronic wounds, the release of DH showed a prolonged profile up to 40 hours, distinct from the results at pH 5.5 and 9.0. These results highlight the capabilities of NaAlg/CA hydrogels created through gamma radiation, combining the biocompatibility and low toxicity of sodium alginate/citric acid, for efficient and sustainable drug delivery, especially valuable in acute wound care where pH-specific therapeutic effectiveness is essential.