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

Lixing Xu; Enhe Bai; Yangbo Zhu; Jiayi Qin; Xiao Du; Haiqin Huang

doi:10.3390/pharmaceutics15010257

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

Pharmaceutics. 2023 Jan 11;15(1):257. doi: 10.3390/pharmaceutics15010257.

Authors

Lixing Xu¹, Enhe Bai², Yangbo Zhu³, Jiayi Qin³, Xiao Du⁴, Haiqin Huang¹

Affiliations

¹ Department of Pharmaceutics, School of Pharmacy, Nantong University, Nantong 226001, China.
² Xiangya International Academy of Translational Medicine, Central South University, Changsha 410013, China.
³ Department of Surgery, Division of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, 79 QingChun Road, Hangzhou 310003, China.
⁴ Department of Pharmacy, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing Medical Center for Clinical Pharmacy, Nanjing 210008, China.

Abstract

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/PASP@CaCO₃) 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/PASP@CaCO₃ hydrogel 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/PASP@CaCO₃ in situ hydrogels significantly relieved oxidative stress injury. Moreover, through Western blot assay, Bai/SA/PASP@CaCO₃ hydrogel 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/PASP@CaCO₃ in 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: baicalin; gastric ulcer; oxidative stress; pH-responsive in situ gelation; sustained release.

Grants and funding

This research was supported by the National Natural Science Foundation of China (No. 81373363), Zhejiang Medical Association Clinical Research Fund (No. 2021ZYC-A67), Zhejiang Medical Science and Technology Project (No. 2023KY704), Zhejiang Traditional Chinese Medicine Science and Technology Project (No. 2023ZR107), and the Postgraduate Research and Innovation Plan Project in Jiangsu Province (KYLX16_1178).