Comparative Design and Evaluation of Chitosan Hydrogels Grafted With Itaconic Acid‐Alginate for Enhanced Linagliptin Delivery

ABSTRACT Dual grafting represents a promising route to enhance the physicochemical properties of chitosan (CS), especially when carried out without the use of chemical cross‐linkers. In this study, CS was grafted with itaconic acid (IA) via free‐radical polymerization and ionotropic gelation method to produce a chitosan‐g‐itaconic acid (CI) hydrogel, which was further grafted with sodium alginate (SA) to synthesize a chitosan‐g‐itaconic acid‐co‐sodium alginate (S) hydrogel. The incorporation of zwitterionic groups enhances pH sensitivity of CI and S hydrogels for drug delivery applications. The grafting process was confirmed using FT‐IR, 1 H NMR, XRD, and EDX. FESEM and AFM analyses revealed increased nano‐porosity and reduction in particle size. The surface morphology of the S hydrogel showed an increase in peaks and voids, supported by skewness (4.479) and kurtosis (29.79) values. UV–Vis spectroscopy revealed Linagliptin (L) loading efficiencies of 38.34% (CI) and 49.56% (S). Cumulative release profiles reached 91% in 45 h (pH 7.4) for CI and 98% in 48 h (pH 1.3) for S. FESEM and XRD further monitored loading and release processes. In conclusion, the combination of dual grafting polymerization and ionotropic gelation enhanced the physical and thermal properties of prepared hydrogels, providing a high pH sensitivity platform for targeting L to the gastrointestinal tract.