Effect of Crosslinking Agents on Chitosan Hydrogel Carriers for Drug Loading and Release for Targeted Drug Delivery

Numerous studies report on chitosan hydrogels in different forms, such as films, porous structures, nanoparticles, and microspheres, for biomedical applications; however, this study concentrates on their modifications with different crosslinking agents and observes their effects on drug loading and releasing capacities. Linear chitosan, along with chitosans crosslinked with two major crosslinkers, i.e., genipin and disulfide, are used to formulate three different hydrogel systems. The crosslinking process is heavily impacted by temperature and pH conditions. Three different drugs, i.e., thymoquinone, gefitinib, and erlotinib, are loaded to the hydrogels in de-ionized water solutions and released in phosphate-buffered solutions; thus, a total of nine combinations are studied and analyzed for their drug loading and releasing capabilities with ultraviolet-visible (UV-Vis) spectroscopy. This study finds that thymoquinone shows the lowest loading efficacy compared to the two other drugs in all three systems. Gefitinib shows stable loading and releasing regardless of crosslinking system, and the genipin-crosslinked system shows stable loading and releasing with all three drug molecules. These experimental results agree well with the findings of our previously published results conducted with molecular dynamics simulations.