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Sustained release of 5-aminosalicylic acid from azoreductase-responsive polymeric prodrugs for prolonged colon-targeted colitis therapy.
- Source :
-
Journal of nanobiotechnology [J Nanobiotechnology] 2024 Aug 06; Vol. 22 (1), pp. 468. Date of Electronic Publication: 2024 Aug 06. - Publication Year :
- 2024
-
Abstract
- Ulcerative colitis (UC) is a challenging inflammatory gastrointestinal disorder, whose therapies encounter limitations in overcoming insufficient colonic retention and rapid systemic clearance. In this study, we report an innovative polymeric prodrug nanoformulation for targeted UC treatment through sustained 5-aminosalicylic acid (5-ASA) delivery. Amphiphilic polymer-based 13.5 nm micelles were engineered to incorporate azo-linked 5-ASA prodrug motifs, enabling cleavage via colonic azoreductases. In vitro, micelles exhibited excellent stability under gastric/intestinal conditions while demonstrating controlled 5-ASA release over 24 h in colonic fluids. Orally administered micelles revealed prolonged 24-h retention and a high accumulation within inflamed murine colonic tissue. At an approximately 60% dose reduction from those most advanced recent studies, the platform halted DSS colitis progression and outperformed standard 5-ASA therapy through a 77-97% suppression of inflammatory markers. Histological analysis confirmed intact colon morphology and restored barrier protein expression. This integrated prodrug nanoformulation addresses limitations in colon-targeted UC therapy through localized bioactivation and tailored pharmacokinetics, suggesting the potential of nanotechnology-guided precision delivery to transform disease management.<br /> (© 2024. The Author(s).)
- Subjects :
- Animals
Mice
NADH, NADPH Oxidoreductases metabolism
Mice, Inbred C57BL
Colitis, Ulcerative drug therapy
Colitis, Ulcerative metabolism
Male
Prodrugs chemistry
Prodrugs pharmacokinetics
Mesalamine chemistry
Mesalamine pharmacokinetics
Nitroreductases metabolism
Colon metabolism
Colon pathology
Polymers chemistry
Micelles
Colitis drug therapy
Colitis metabolism
Delayed-Action Preparations chemistry
Subjects
Details
- Language :
- English
- ISSN :
- 1477-3155
- Volume :
- 22
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Journal of nanobiotechnology
- Publication Type :
- Academic Journal
- Accession number :
- 39103846
- Full Text :
- https://doi.org/10.1186/s12951-024-02724-w