4.5 Article

On-demand reconstitutable hyaluronic acid-doped azathioprine microcrystals effectively ameliorate ulcerative colitis via selective accumulation in inflamed tissues

Journal

BIOMATERIALS SCIENCE
Volume 10, Issue 22, Pages 6500-6509

Publisher

ROYAL SOC CHEMISTRY
DOI: 10.1039/d2bm01137a

Keywords

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Funding

  1. National Research Foundation of Korea(NRF) - Korea government(MSIT) [NRF-2022R1A2C2004340]

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In this study, an on-demand reconstitutable drug delivery system for ulcerative colitis (UC) treatment was developed. The system successfully addressed the issue of premature drug release and systemic absorption by incorporating hyaluronic acid (HA)-doped drug microcrystals into a protective layer. The system demonstrated potent anti-inflammatory effects in a colitis model without causing systemic toxicity.
Although CD44-targeted delivery of pure drug microcrystals of azathioprine (AZA) could be a desirable approach to treat ulcerative colitis (UC), premature drug release and systemic absorption before reaching the colitis region remain a major obstacle. In this study, to overcome these limitations, we developed on-demand reconstitutable HA-doped AZA microcrystals (EFS/HA-AZAs) via incorporating hyaluronic acid (HA)-doped AZA microcrystals (HA-AZAs) into a Eudragit FS (EFS) microcomposite. Since EFS acts as a protective layer, the premature release of AZA in the simulated conditions of the stomach and small intestine was substantially reduced, while HA-AZAs were successfully reconstituted from the EFS/HA-AZAs in the colonic environment, resulting from the pH-triggered dissolution of EFS. After complete reconstitution of HA-AZAs in the colon, HA-AZAs selectively accumulated in the inflamed region via the HA-CD44 interaction. Owing to successful colitis-targeted delivery, EFS/HA-AZAs showed potent anti-inflammatory effects in a dextran sulfate sodium-induced murine colitis model within 7 days without systemic toxicity. These results suggest that EFS/HA-AZAs could be a promising drug delivery system for UC treatment.

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