Enteric coating of halloysite nanotube/ o-butyrylated chitosan microspheres for the co-delivery of paeoniflorin and butyric acid to colon

This study aims to achieve co-delivery of paeoniflorin (PF) and butyric acid (BA) to the colon through Eudragit S100 (EUS100)-coated halloysite nanotube/o-butyryl chitosan microspheres (EUS100-HNT-BUCHNPs). Obutyrylated chitosan (BUCH) was prepared by the acylation reaction of chitosan (CH) and butyric anhydride with methane sulfonic acid as a catalyst. PF-loaded halloysite nanotube/o-butyrylated chitosan microspheres (HNTBUCHNPs) were prepared by emulsion crosslinking with glutaraldehyde as the crosslinking agent and then coated with EUS100 using the emulsion solvent evaporation method. X-ray photoelectron spectroscopy (XPS) and scanning electron microscopy results indicated the presence of EUS100 coating on the surface of HNTBUCHNPs. In vitro release studies demonstrated that the EUS100 coating effectively prevented the release of PF and BA at pH 1.2, while the halloysite nanotube slowed down PF release at pH 6.8. Sequential release experiments in different pH media showed lower release of PF and BA at pH 1.2 and pH 6.8, and higher release at pH 7.4, reaching approximately 80 % and 85 %, respectively. Gastrointestinal tract retention studies in mice confirmed that EUS100-HNT-BUCHNPs reduced the release of PF and BA in the upper digestive tract, facilitating delivery to the colon. In vivo and in vitro results indicated efficient transport of PF and BA to the colon, suggesting the potential of EUS100-HNT-BUCHNPs as colon-targeted carriers for PF and BA.