Oral delivery of pH-sensitive nanoparticles loaded Celastrol targeting the inflammatory colons to treat ulcerative colitis

The incidence of ulcerative colitis (UC) is rapidly rising worldwide. Oral drug delivery system is a promising approach for treating UC, but it often fails to accumulate to the inflammatory lesions, thus, it is impressive to develop a colon-targeted oral delivery system for preventing systemic toxic...

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Bibliographic Details
Published in:Journal of tissue engineering 2024-01, Vol.15, p.20417314241265892
Main Authors: Zhao, Yue, Yao, Yinlian, Fan, Shilong, Shen, Xin, Chai, Xingxing, Li, Zimin, Zeng, Jiachun, Pi, Jiang, Zhou, Zhikun, Huang, Gonghua, Jin, Hua
Format: Article
Language:English
Subjects:
Chitosan
Colon
Decomposition reactions
Drug delivery
Drug delivery systems
Herbal medicine
Inflammatory bowel disease
Inflammatory bowel diseases
Leukocytes (neutrophilic)
Lymphocytes
Lymphocytes T
Macrophages
Mannose
Nanoparticles
Oral administration
Original
pH effects
Polylactide-co-glycolide
Reactive oxygen species
Scavenging
Toxicity
Tumor necrosis factor-α
Ulcerative colitis
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Summary:The incidence of ulcerative colitis (UC) is rapidly rising worldwide. Oral drug delivery system is a promising approach for treating UC, but it often fails to accumulate to the inflammatory lesions, thus, it is impressive to develop a colon-targeted oral delivery system for preventing systemic toxicity and maintaining UC therapeutics. Here, a negative-charged PLGA nanoparticle system was designed to encapsulate celastrol (Cel), and then chitosan and mannose were coated on the surface of the nanoparticles (MC@Cel-NPs) to endow these nanoparticles with the mucosal adsorption and macrophage targeting abilities. MC@Cel-NPs demonstrate excellent resist decomposition ability against the strong acidic gastrointestinal environment, and accumulates in the specific inflammatory sites through the affinity of electrostatic reaction. After releasing the payload, MC@Cel-NPs could remarkably alleviate the colon inflammation, which was evidenced by the decrease in pro-inflammatory cytokines TNF-α, IL-1β, and IL-6 in both blood and colon sections, and scavenging reactive oxygen species (ROS) in colon cells, including macrophage, neutrophil, T cell, and B cell. This nanoparticle system provided a new approach for treating UC through a Chinese herbal ingredient-related oral delivery manner.
ISSN:2041-7314
2041-7314
DOI:10.1177/20417314241265892