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

Based on the biocompatibility and macrophage targeting of natural polysaccharides, combined with the physiological 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 dru...

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Bibliographic Details
Published in:Carbohydrate polymers 2023-08, Vol.313, p.120884-120884, Article 120884
Main Authors: Zhang, Ying, Ma, Ruirui, You, Cuiyu, Leng, Xue, Wang, Danyang, Deng, Shujing, He, Binyang, Guo, Ziyang, Guan, Zelin, Lei, Hengyu, Yu, Jie, Zhou, Qinyuan, Xing, Jianfeng, Dong, Yalin
Format: Article
Language:English
Subjects:
Chitosan - pharmacology
Colitis - drug therapy
Colitis - pathology
Colitis, Ulcerative - drug therapy
Colitis, Ulcerative - pathology
Colon
Colon targeting
Dexamethasone
Drug Delivery Systems
Humans
Hyaluronic Acid - pharmacology
Macrophage polarization
Macrophages
Nano-in-micro delivery system
Nanoparticles
Natural polysaccharides
Ulcerative colitis
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Summary:Based on the biocompatibility and macrophage targeting of natural polysaccharides, combined with the physiological 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 macrophages. HA/CS/Dex nanoparticles (HCD NPs) are ingested by macrophages via CD44 receptor-mediated endocytosis 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. [Display omitted]
ISSN:0144-8617
1879-1344
DOI:10.1016/j.carbpol.2023.120884