Construction of a biocompatible alginate-based hydrogel cross-linked by Diels–Alder chemistry for controlled drug release

Abstract

With the use of the Diels-Alder (DA) reaction, we were able to effectively develop and describe a hydrogel based on alginate that is chemically cross-linked. First, an alginic acid hydrazide intermediate (Alg-Hd) was synthesized; next, the furan-modified alginate (AlgF) was synthesized as the diene part by reacting furoyl chloride with the free NH2 groups of the Alg-Hd. Maleimide-functionalized alginate (Alg-MA) was made by letting 3-maleimidopropionic acid react with the NH2 groups of Alg-Hd through carbodiimide coupling, which is considered the dienophil part. The final hydrogel network was cross-linked from the two different alginate derivatives that perform well together. Elements analysis and 1H NMR spectroscopy were used to figure out that the degree of functionalization (DF) for the Alg-F derivative was between 23 and 53% and that for the Alg-MA derivative was between 21 and 55%. The microstructure, crystallinity, swelling capacity, and rheological behavior of the hydrogel in its as-designed form were examined. The pH sensitivity, biocompatibility, and other properties of hydrogel seemed good for medical uses, especially as a way to deliver drugs like gliclazide.