Oral colon-targeted responsive chitosan/pectin-based nanoparticles propels the application of tofacitinib in colitis therapy

Oral colon-targeted responsive chitosan/pectin-based nanoparticles propels the application of tofacitinib in colitis therapy

Abstract Tofacitinib (Tof), a commercially available pan-Janus kinases inhibitor, is approved for the treatment of moderate to severe ulcerative colitis. However, its clinical application is limited due to dose-dependent systemic side effects. The present study aims to develop an efficient oral colo...

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Bibliographic Details
Main Authors: Chunfei Wu, Chuanlin Bi, Geun-soo Kim, Zizhen Yang, Shuao Li, Tong Dai, Xiaoyu Wu, Jiaojiao Tan, Ningning He, Shangyong Li
Format: Article
Language:English
Published: Nature Portfolio 2025-01-01
Series:Scientific Reports
Subjects:
Ulcerative colitis
Colon-targeted drug delivery
pH-sensitive release
Enzymatic-triggered release
Online Access:https://doi.org/10.1038/s41598-024-84322-2
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Summary:Abstract Tofacitinib (Tof), a commercially available pan-Janus kinases inhibitor, is approved for the treatment of moderate to severe ulcerative colitis. However, its clinical application is limited due to dose-dependent systemic side effects. The present study aims to develop an efficient oral colon-targeted drug delivery systems using prebiotic pectin (Pcn) and chitosan (Csn) polysaccharides as a shell, with Tof loaded into a Bovine Serum Albumin (BSA) core, and improving it with chondroitin sulfate (Chs), thus constructing Tof@BSA-Chs-CP nanoparticles (NPs). Our results suggest that the pH-sensitive characteristics of the Pcn/Csn shell contribute to its capacity for attenuating absorption and systemic diffusion in the gastrointestinal tract, and exhibiting targeted localization at inflamed colonic sites in mice. Additionally, the gut microbiota-secreted polysaccharide-degrading enzyme acts as the triggering agent for Pcn/Csn shell degradation. In mice colitis models, we demonstrated that oral administration of Tof@BSA-Chs-CP NPs effectively ameliorated colitis and expedited its resolution by modulating the expression of pro-inflammatory cytokines and immune regulatory factors. Collectively, our synthetic NPs demonstrate the promising potential of Tof for the therapy of UC.
ISSN:2045-2322

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