Abstract

The low stability of β-lactoglobulin (βlg) under gastric conditions decreases the protein amount reaching the small intestine. Thus, it is crucial to develop a vehicle that can protect βlg from the stomach harsh acidity and enable its sustained and prolonged release in the small intestine. Herein, a fresh hydrogel composed of salecan-g-poly(N,N-dimethylaminoethyl acrylate) (PDMAEA) and nutgall tannic acid (TA) was fabricated by microwave-assisted polymerization. The incorporation of salecan into hydrogels markedly affected the hydrogels' thermal stability, microstructure, and mechanical strength. Particularly, the multiple phenolic groups of TA can form complexes with βlg, and this enables the highly effective loading of proteins. As expected, βlg not only achieved effective entrapment into the hydrogels but also achieved a tunable and pH-controlled release. Such a release profile will enable βlg protection in the stomach and its targeted release in the small intestine. Increasing the salecan content dramatically enhanced the βlg release in simulated intestinal fluid (SIF). Furthermore, the βlg release was driven by Fickian diffusion in simulated gastric fluid (SGF), but the mechanism changed to non-Fickian diffusion in SIF. The release mechanism excellently matched Ritger-Peppas model. Overall, these results indicate that TA/salecan-g-PDMAEA hydrogels hold great potential for protein delivery in the gastrointestinal tract.

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