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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Nature Portfolio
2025-01-01
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| Online Access: | https://doi.org/10.1038/s41598-024-84322-2 |
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| author | Chunfei Wu Chuanlin Bi Geun-soo Kim Zizhen Yang Shuao Li Tong Dai Xiaoyu Wu Jiaojiao Tan Ningning He Shangyong Li |
| author_facet | Chunfei Wu Chuanlin Bi Geun-soo Kim Zizhen Yang Shuao Li Tong Dai Xiaoyu Wu Jiaojiao Tan Ningning He Shangyong Li |
| author_sort | Chunfei Wu |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-0f265c9c5de74404a7b4815b85f33d59 |
| institution | Kabale University |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj-art-0f265c9c5de74404a7b4815b85f33d592025-01-12T12:22:06ZengNature PortfolioScientific Reports2045-23222025-01-0115111110.1038/s41598-024-84322-2Oral colon-targeted responsive chitosan/pectin-based nanoparticles propels the application of tofacitinib in colitis therapyChunfei Wu0Chuanlin Bi1Geun-soo Kim2Zizhen Yang3Shuao Li4Tong Dai5Xiaoyu Wu6Jiaojiao Tan7Ningning He8Shangyong Li9Medical School, Qingdao Huanghai UniversityQingdao Institute for Food and Drug ControlSchool of Basic Medicine, Qingdao Medical College, Qingdao UniversitySchool of Basic Medicine, Qingdao Medical College, Qingdao UniversitySchool of Basic Medicine, Qingdao Medical College, Qingdao UniversitySchool of Basic Medicine, Qingdao Medical College, Qingdao UniversitySchool of Basic Medicine, Qingdao Medical College, Qingdao UniversityMedical School, Qingdao Huanghai UniversitySchool of Basic Medicine, Qingdao Medical College, Qingdao UniversitySchool of Basic Medicine, Qingdao Medical College, Qingdao UniversityAbstract 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.https://doi.org/10.1038/s41598-024-84322-2Ulcerative colitisColon-targeted drug deliverypH-sensitive releaseEnzymatic-triggered release |
| spellingShingle | Chunfei Wu Chuanlin Bi Geun-soo Kim Zizhen Yang Shuao Li Tong Dai Xiaoyu Wu Jiaojiao Tan Ningning He Shangyong Li Oral colon-targeted responsive chitosan/pectin-based nanoparticles propels the application of tofacitinib in colitis therapy Scientific Reports Ulcerative colitis Colon-targeted drug delivery pH-sensitive release Enzymatic-triggered release |
| title | Oral colon-targeted responsive chitosan/pectin-based nanoparticles propels the application of tofacitinib in colitis therapy |
| title_full | Oral colon-targeted responsive chitosan/pectin-based nanoparticles propels the application of tofacitinib in colitis therapy |
| title_fullStr | Oral colon-targeted responsive chitosan/pectin-based nanoparticles propels the application of tofacitinib in colitis therapy |
| title_full_unstemmed | Oral colon-targeted responsive chitosan/pectin-based nanoparticles propels the application of tofacitinib in colitis therapy |
| title_short | Oral colon-targeted responsive chitosan/pectin-based nanoparticles propels the application of tofacitinib in colitis therapy |
| title_sort | oral colon targeted responsive chitosan pectin based nanoparticles propels the application of tofacitinib in colitis therapy |
| topic | Ulcerative colitis Colon-targeted drug delivery pH-sensitive release Enzymatic-triggered release |
| url | https://doi.org/10.1038/s41598-024-84322-2 |
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