Sodium Butyrate‐Loaded Microspheres With Enhanced Bioavailability for Targeted Treatment of Intestinal Barrier Injury

Abstract Intestinal barrier dysfunction is related to diseases such as inflammatory bowel disease (IBD) and severe acute pancreatitis (SAP). Butyrate and its derivatives (e.g., sodium butyrate (SB)) can alleviate gut inflammatory responses. Nevertheless, these substances usually cannot fully exert protective effects due to low bioavailability. This research aimed to offer microspheres for treating intestinal barrier injury. Sodium alginate solution is prepared to dissolve SB, followed by mixing with chitosan (CS)‐protocatechuic aldehyde (PA)/calcium chloride solution. The required CS‐PA/calcium alginate/SB (CPC/SB) microspheres are formed in this manner. Subsequently, the therapeutic effects of CPC/SB microspheres on intestinal barrier injury through in vivo dextran sulfate sodium salt (DSS)‐induced IBD and sodium taurocholate (STC)‐induced SAP models is explored. Results: The CPC/SB microspheres exhibited excellent antioxidant properties. In vivo bioluminescence imaging experiment confirmed the microspheres effectively targeted the inflammatory gut in IBD. Further in vivo experimental results indicated the microspheres significantly repaired intestinal barrier damage, exerting protective effects in IBD and SAP. Additionally, 16S rDNA sequencing explained the microspheres can regulate the balance between harmful and beneficial bacteria (such as Alistipes, Odoribacter, and Rikenellaceae RC9). This study provides a possible synthetic strategy of microsphere carriers to serve as a potential therapeutic tool for intestinal barrier injury.