Inflammation-triggered local drug release ameliorates colitis by inhibiting dendritic cell migration and Th1/Th17 differentiation.
Animals
Cell Differentiation
/ drug effects
Cell Movement
/ drug effects
Colitis
/ drug therapy
Dendritic Cells
/ cytology
Disease Models, Animal
Drug Delivery Systems
Drug Liberation
Immunosuppressive Agents
/ administration & dosage
Inflammation
/ drug therapy
Mice
Mice, Inbred C57BL
Microspheres
Polymethacrylic Acids
/ chemistry
Reactive Oxygen Species
/ metabolism
Tacrolimus
/ administration & dosage
Th1 Cells
/ cytology
Th17 Cells
/ cytology
Colitis
Dendritic cell migration
FK506
ROS-responsive microspheres
Reactive oxygen species (ROS)
Journal
Journal of controlled release : official journal of the Controlled Release Society
ISSN: 1873-4995
Titre abrégé: J Control Release
Pays: Netherlands
ID NLM: 8607908
Informations de publication
Date de publication:
28 12 2019
28 12 2019
Historique:
received:
22
07
2019
revised:
27
10
2019
accepted:
01
11
2019
pubmed:
7
11
2019
medline:
27
10
2020
entrez:
6
11
2019
Statut:
ppublish
Résumé
Enteric-coated formulations using Eudragit® polymers have been extensively used for delivering drugs to the lower gastrointestinal tract. However, these drug-delivery systems cannot accurately deliver the therapeutic cargoes to colon because of early degradation of the polymers at alkaline pH of the small intestine. Here, we describe a precise method of delivering drugs to inflammation sites in colon using an oral drug delivery system. Tacrolimus (FK506)-loaded microspheres were prepared using a thioketal-based polymer that releases drug in response to reactive oxygen species (ROS), which are abundantly produced at the sites of inflammation in acute colitis. Orally-administered FK506-loaded thioketal microspheres (FK506-TKM) led to a substantial accumulation of FK506 in inflamed colon and effectively alleviated dextran-sulfate sodium (DSS)-induced murine colitis. At the molecular level, FK506-TKM significantly inhibited infiltration of CD4
Identifiants
pubmed: 31689461
pii: S0168-3659(19)30621-2
doi: 10.1016/j.jconrel.2019.11.001
pii:
doi:
Substances chimiques
Immunosuppressive Agents
0
Polymethacrylic Acids
0
Reactive Oxygen Species
0
methylmethacrylate-methacrylic acid copolymer
25086-15-1
Tacrolimus
WM0HAQ4WNM
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
138-149Informations de copyright
Copyright © 2019 Elsevier B.V. All rights reserved.