Fabrication, optimization, and in vitro validation of penicillin-loaded hydrogels for controlled drug delivery

Bacterial infections present a major global challenge. Penicillin, a widely used antibiotic known for its effectiveness and safety, is frequently prescribed. However, its short half-life necessitates multiple high-dose daily administrations, leading to severe side-effects. Therefore, this study aims to address these issues by developing hydrogels which control the release of penicillin and alleviate its adverse effects. Various combinations of aspartic acid and acrylamide were crosslinked by N', N'-methylene bisacrylamide through a free radical polymerization process to prepare aspartic acid/acrylamide (Asp/Am) hydrogels. The fabricated hydrogels underwent comprehensive characterization to assess physical properties and thermal stability. The soluble and insoluble fractions and porosity of the synthesized matrix were evaluated by sol-gel and porosity studies. Gel fraction was estimated at 88-96%, whereas sol fraction was found 12-4% and porosity found within the 63-78% range for fabricated hydrogel formulations. Maximum swelling and drug release were seen at pH 7.4, demonstrating a controlled drug release from hydrogel networks. The results showed that swelling, porosity, gel fraction, and drug release increased with higher concentrations of aspartic acid and acrylamide. However, integration of N', N'-methylene bisacrylamide exhibited the opposite effect on swelling and porosity, while increasing gel fraction. All formulations followed the Korsymer-Peppas model of kinetics with 'r' values within the range of 0.9740-0.9980. Furthermore, the cytotoxicity study indicated an effective and safe use of hydrogel because the cell viability was higher than 70%. Therefore, these prepared hydrogels show promise candidates for controlled release of Penicillin and are anticipated to be valuable in clinical applications.