Pristine and cross-linked gelatin aerogels of pH-responsive hydration and swelling

• High-porosity sustainable biopolymer aerogels with fibril-like nanostructure. • Young’s modulus from 35 to 105 MPa, increasing with higher amount of cross-linker. • Significantly higher water uptake and faster swelling under acidic conditions. • Hydration properties explored by nuclear magnetic resonance (NMR) relaxometry. • Retarded drug release in neutral media and fast solubilization in acidic media. Protein aerogels, derived from natural sources such as plants and animals, are sustainable and biocompatible advanced materials with significant potential for applications in the environmental, food, and pharmaceutical industries. In this study, food-grade gelatin was used to produce highly porous aerogels. Gelatin was employed either in its native form or chemically cross-linked with glutaraldehyde (GTA). Hydrogels were synthesized through a simple sol-gel process, transferred to methanol, and then dried using supercritical CO 2 to obtain mesoporous aerogels. The chemical structure of the aerogels was characterized using solid-state nuclear magnetic resonance (ssNMR) and infrared (IR) spectroscopy methods. Their nanoscale morphologies were explored by scanning electron microscopy (SEM), N 2 -sorption porosimetry, and small-angle neutron scattering (SANS). The macroscopic water uptake and swelling of the gelatin aerogels were investigated at different pH values, while the corresponding nanoscale hydration and wetting mechanisms were explored using NMR relaxometry. Lastly, the drug loratadine was impregnated into the pure gelatin aerogel to assess its potential for drug delivery applications. The rate and mechanism of in vitro drug release exhibit a strong correlation with the pH-dependent swelling and dissolution of the aerogel. These findings suggest that pure gelatin aerogels are promising candidates for pH-sensitive oral drug delivery systems.