Oral Delivery of siRNA Using Fluorinated, Small-Sized Nanocapsules toward Anti-Inflammation Treatment

Oral Delivery of siRNA Using Fluorinated, Small-Sized Nanocapsules toward Anti-Inflammation Treatment

© 2023 Wiley-VCH GmbH.

Détails bibliographiques
Publié dans:Advanced materials (Deerfield Beach, Fla.). - 1998. - 35(2023), 11 vom: 11. März, Seite e2206821
Auteur principal: Wei, Yuansong (Auteur)
Autres auteurs: Li, Xudong, Lin, Juanhui, Zhou, Yang, Yang, Jiandong, Hou, Mengying, Wu, Fan, Yan, Jing, Ge, Chenglong, Hu, Duanmin, Yin, Lichen
Format: Article en ligne
Langue:English
Publié: 2023
Accès à la collection:Advanced materials (Deerfield Beach, Fla.)
Sujets:Journal Article anti-inflammatory therapy fluorinated nanocapsules intestinal absorption mucus penetration oral siRNA delivery Nanocapsules RNA, Small Interfering Tumor Necrosis Factor-alpha Anti-Inflammatory Agents
Description
Résumé:© 2023 Wiley-VCH GmbH.
Oral delivery of small interfering RNA (siRNA) provides a promising paradigm for treating diseases that require regular injections. However, the multiple gastrointestinal (GI) and systemic barriers often lead to inefficient oral absorption and low bioavailability of siRNA. Technologies that can overcome these barriers are still lacking, which hinders the clinical potential of orally delivered siRNA. Herein, small-sized, fluorinated nanocapsules (F-NCs) are developed to mediate efficient oral delivery of tumor necrosis factor α (TNF-α) siRNA for anti-inflammation treatment. The NCs possess a disulfide-cross-linked shell structure, thus featuring robust stability in the GI tract. Because of their small size (≈30 nm) and fluorocarbon-assisted repelling of mucin adsorption, the best-performing F3 -NCs show excellent mucus penetration and intestinal transport capabilities without impairing the intestinal tight junction, conferring the oral bioavailability of 20.4% in relative to intravenous injection. The disulfide cross-linker can be cleaved inside target cells, causing NCs dissociation and siRNA release to potentiate the TNF-α silencing efficiency. In murine models of acute and chronic inflammation, orally delivered F3 -NCs provoke efficient TNF-α silencing and pronounced anti-inflammatory efficacies. This study therefore provides a transformative strategy for oral siRNA delivery, and will render promising utilities for anti-inflammation treatment
Description:Date Completed 21.03.2023
Date Revised 21.03.2023
published: Print-Electronic
Citation Status MEDLINE
ISSN:1521-4095
DOI:10.1002/adma.202206821