Abstract
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-κB 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.
Highlights
Ulcerative colitis (UC) is a chronic idiopathic inflammatory disease that continuously occurs from the distal to the proximal ends of the colon
88.5~94.3% of mucin was adsorbed by trimethyl chitosan (TMC), while less than 50% of mucin could be adsorbed by chitosan
Given that the pectin layer of Cel/PT-LbL Lipo was degraded by the intestinal flora first, we investigate the role of TMC Lipo on the cellular uptake of payloads, the fluorescent dye coumarin 6 (C6 ) was loaded into TMC Lipo
Summary
Ulcerative colitis (UC) is a chronic idiopathic inflammatory disease that continuously occurs from the distal to the proximal ends of the colon. It has been shown that nano-scaled drug delivery systems may be promising approaches for efficient colon delivery, with potentially effective outcomes in the treatment of UC [13]; the development of a nanocarrier with good GI stability and ideal colon tissue permeability after oral administration remains highly challenging. Like chitosan [15], pectin, hyaluronic acid, and sodium alginate, have been used to coat the surface of drug delivery systems This has resulted in enhanced GI stability and colon targeting [16,17,18,19,20]. Oral administration delivery of TMC coated liposomes acts against UC by protecting the colonic epithelial cells from damage and anti-inflammation. Pectin-TMC coated liposomes acts against UC by protecting the colonic epithelial cells from damage and anti-inflammation
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