4.7 Article

Hyaluronic acid modified oral drug delivery system with mucoadhesiveness and macrophage-targeting for colitis treatment

Journal

CARBOHYDRATE POLYMERS
Volume 313, Issue -, Pages -

Publisher

ELSEVIER SCI LTD
DOI: 10.1016/j.carbpol.2023.120884

Keywords

Ulcerative colitis; Dexamethasone; Natural polysaccharides; Nano-in-micro delivery system; Colon targeting; Macrophage polarization

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Based on the biocompatibility and macrophage targeting of natural polysaccharides, oral colon-targeted nano-in-micro drug delivery systems loaded with dexamethasone (Dex) were prepared for ulcerative colitis (UC) treatment. These systems regulated the M1/M2 polarization of intestinal macrophages and showed promising colon-targeting properties. They exerted significant anti-UC effects and have potential application in UC treatment.
Based on the biocompatibility and macrophage targeting of natural polysaccharides, combined with the physi-ological and pathological characteristics of the gastrointestinal tract and colonic mucosa of ulcerative colitis (UC), we prepare dexamethasone (Dex)-loaded oral colon-targeted nano-in-micro drug delivery systems coated with multilayers of chitosan (CS), hyaluronic acid (HA), and finally Eudragit S100 (ECHCD MPs) using a layer-by-layer coating technique for UC treatment through regulating the M1/M2 polarization of intestinal macro-phages. HA/CS/Dex nanoparticles (HCD NPs) are ingested by macrophages via CD44 receptor-mediated endo-cytosis to regulate M1-to-M2 macrophage polarization and exert anti-inflammatory effects. Moreover, ECHCD MPs show better colon-targeting properties than Dex-loaded chitosan nanoparticles (CD NPs) and HCD NPs which is demonstrated by stronger mucoadhesion to inflamed colon tissues. After oral administration, ECHCD MPs exert significant anti-UC effects. Therefore, ECHCD MPs are proven to be as promising oral colon-targeting drug delivery systems for Dex and have potential application in UC treatment.

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