A novel pH-responsive berberine-loaded attapulgite microsphere for IBD therapy via the regulation of gut immunity and flora

Inflammatory bowel disease ( IBD) is an idiopathic, lifelong, and devastating chronic inflammatory disease of the gastrointestinal tract. Berberine, an alkaloid extracted from the Chinese herb Huanglian, is a pharmaceutical ingredient with antibacterial, anti-inflammatory, and antiviral pharmacological effects in Chinese medicine. However, direct administration of berberine requires high doses due to its low bioavailability and high waste in the stomach. In this study, we prepared berberine-loaded pH-responsive Eudragit® FS 30D-attapulgite (FS-ATT) microspheres for the targeted treatment of colitis. The microspheres had pH-responsive release behavior, with minimal berberine release (about 5.97%) in simulated gastric fluid and high berberine release in simulated colonic fluid (about 69.27%). In addition, it was revealed by in vivo biological evaluations that, compared with drugs in an equivalent solution form taken orally, a significant improvement in IBD symptoms was observed after oral administration of drug-loaded FS-ATT microspheres, leading to an increase in the diversity of intestinal microbiota, inhibition of inflammatory cytokines, and enhanced therapeutic effects of berberine. The pH-responsive FS-ATT microspheres could offer a promising drug delivery platform for managing and treating many gastrointestinal diseases.