Colonic Delivery of Celastrol-Loaded Layer-by-Layer Liposomes with Pectin/Trimethylated Chitosan Coating to Enhance Its Anti-Ulcerative Colitis Effects

Herein, a flexible oral colon-targeting delivery system, mediated by electrostatic layer-by-layer alternate deposition with pectin-trimethyl chitosan (TMC) onto liposomes-loading celastrol (Cel/PT-LbL Lipo), was fabricated to enhance anti-UC efficacy. Along with layer-by-layer coating, Cel/Lipo exhibited surface charge reversal, a slight increase in particle size, and a sustained drug release profile in a simulative gastrointestinal tract medium. Based on its bilayer coating of polysaccharides, Cel/PT-LbL Lipo alleviated cytotoxicity of celastrol in colon epithelial NCM460 cells. Due to the strong mucoadhesion of TMC with mucin, PT-LbL Lipo benefited colon localization and prolonged retention ability of its payloads. Ultimately, Cel/PT-LbL Lipo significantly mitigated colitis symptoms and accelerated colitis repair in DSS-treated mice by regulating the levels of pro-inflammatory factors related to the TLR4/MyD88/NF-kappa B signaling pathway. Collectively, this study demonstrates that the pectin/trimethylated chitosan coating may allow for Cel/PT-LbL Lipo to function as a more beneficial therapeutic strategy for UC treatment.

Automated summary

A flexible oral colon-targeting delivery system mediated by pectin-trimethyl chitosan coating was developed to enhance anti-UC efficacy. The system, with a bilayer coating of polysaccharides, reduced drug cytotoxicity, improved mucosal adhesion, and prolonged drug retention in the colon. Ultimately, this system significantly alleviated colitis symptoms and accelerated colitis repair in mice by regulating inflammation-related factors.