pH-Responsive Hydrogel as a Potential Oral Delivery System of Baicalin for Prolonging Gastroprotective Activity

Gastric ulcer is one of the most common gastrointestinal diseases, and natural products have obvious advantages in the treatment of gastrointestinal diseases. Baicalin (Bai) extracted from scutellaria baicalensis exhibits anti-inflammatory, antioxidant, and anti-apoptotic activities. Herein, a pH-responsive sodium alginate/polyaspartate/CaCO3(SA/[email protected]3) in situ hydrogel was established for the oral delivery of Bai. In this study, we detected the gelling properties, mechanical strength, in vitro erosion, and in vitro release behavior of the hydrogels. Meanwhile, the efficiency of Bai/SA/[email protected]3hydrogel on ethanol-induced acute gastric ulcers, acetic acid-induced chronic gastric ulcers, and H2O2-stimulated human gastric epithelial GES-1 cells was explored. The pathological examination revealed that Bai-loaded hydrogel alleviated acute and chronic gastric ulcers. In vivo and in vitro results further confirmed that Bai/SA/[email protected]3in situ hydrogels significantly relieved oxidative stress injury. Moreover, through Western blot assay, Bai/SA/[email protected]3hydrogel was also found to dramatically increase the proteins levels of NRF2, HO-1, and Bcl2, and reduce levels of p-JNK, cleaved-caspase-3 and Bax; through flow cytometry, it was observed to significantly inhibit the H2O2-induced apoptosis of GES-1 cells. Importantly, the Bai/SA/[email protected]3in situ hydrogel system showed better anti-gastric ulcer efficiency than free drug, and could serve as a potential drug delivery system for the clinical treatment of gastric ulcers.Keywords:gastric ulcer;pH-responsive in situ gelation;baicalin;sustained release;oxidative stress