Orally administrated nucleotide-delivery particles from microfluidics for inflammatory bowel disease treatment AITranslate

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DOI：https://doi.org/10.1016/j.apmt.2021.101231

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Oral administration route for treating inflammatory bowel disease (IBD) is one of the most convenient methods, especially for the chemical molecular drugs and biologics. Attempts to develop applicable oral administration method tend to focus on the construction of functional microcarriers through simple operations and employing innovative but accessible materials. Here, we report a pH-sensitive drug delivery system by microfluidics for oral administration of therapeutic antisense oligonucleotide (ASO) against TNF-α (TNF-α ASO) to treat the IBD. The microfluidics-derived cationic Konjac glucomannan (cKGM) & ASO Nanocomplex-loaded gelatin methacryloyl (GelMA) microparticles are coated by the acid-insoluble shells, i.e. Eudragit FS30D (GelMA MS/EFS & Nano ASO), which can prevent the encapsulated drugs from being early released in the stomach or small intestine, and enhance their selective accumulation in colon, as well as facilitate the macrophage uptake of drugs via receptor-mediated phagocytosis. It is demonstrated that our designed drug-loaded microcarriers can significantly reduce the production of TNF-α in the nidus of the colitis animal models, and effectively alleviate the symptoms of colitis in the mice after oral administration. These properties indicated that this therapeutic ASO oral delivery system can be a promising approach in treating colon-associated diseases. Graphical abstract Download : Download high-res image (219KB) Download : Download full-size image