Crosslinked Biodegradable Hybrid Hydrogels Based on Poly(ethylene glycol) and Gelatin for Drug Controlled Release

A series of hybrid hydrogels of poly(ethylene glycol) (PEG) were synthesized using gelatin as a crosslinker and investigated for controlled delivery of the first-generation cephalosporin antibiotic, Cefazedone sodium (CFD). A commercially available 4-arm-PEG-OH was first modified to obtain four-arm-PEG-succinimidyl glutarate (4-arm-PEG-SG), which formed the gelatin-PEG composite hydrogels (S_nN_m) through crosslinking with gelatin. To regulate the drug delivery, S_nN_m hydrogels with various solid contents and crosslinking degrees were prepared. The effect of solid contents and crosslinking degrees on the thermal, mechanical, swelling, degradation, and drug release properties of the hydrogels were intensively investigated. The results revealed that increasing the crosslinking degree and solid content of S_nN_m could not only enhance the thermal stability, swelling ratio (SR), and compression resistance capacity of S_nN_m but also prolong the degradation and drug release times. The release kinetics of the S_nN_m hydrogels were found to follow the first-order model, suggesting that the transport rate of CFD within the matrix of hydrogels is proportional to the concentration of the drug where it is located. Specifically, S₁N₁-III showed 90% mass loss after 60 h of degradation and a sustained release duration of 72 h. The cytotoxicity assay using the MTT method revealed that cell viability rates of S₁N₁ were higher than 95%, indicating excellent cytocompatibility. This study offers new insights and methodologies for the development of hydrogels as biomedical composite materials.