Colon-targeted dexamethasone microcrystals with pH-sensitive chitosan/alginate/Eudragit S multilayers for the treatment of inflammatory bowel disease

Abstract

Oral colon-targeted drug delivery has gained popularity as an effective strategy for treatment of inflammatory bowel disease (IBD). In this study, we prepared colon-targeted dexamethasone microcrystals (DXMCs) coated with multilayers of chitosan oligosaccharide (CH), alginate (AG), and finally Eudragit S 100 (ES) (ES₁AG₄CH₅-DXMCs) using a layer-by-layer (LBL) coating technique. Particle size, surface charge, in vitro drug release, and in vivo anti-inflammatory activity of ES₁AG₄CH₅-DXMCs were evaluated. ES₁AG₄CH₅-DXMCs had an average particle size of 2.34 ± 0.19 μm and a negative surface charge of - 48 ± 9 mV. ES₁AG₄CH₅-DXMCs demonstrated pH-dependent dexamethasone release, avoiding initial burst drug release in acidic pH conditions of the stomach and small intestine, and providing subsequent sustained drug release in the colonic pH. Importantly, ES₁AG₄CH₅-DXMCs exhibited a significant therapeutic activity in a mouse model of colitis compared to other DXMCs. Overall, the LBL-coated DXMCs presented here could be a promising colon-targeted therapy for IBD.

Keywords: Colon-targeted drug delivery; Dexamethasone; Inflammatory bowel disease; Layer-by-layer coating; Microcrystals.