Seegobin, Nidhi;
McCoubrey, Laura E;
Vignal, Cecile;
Waxin, Christophe;
Abdalla, Youssef;
Fan, Yue;
Awad, Atheer;
... Basit, Abdul W; + view all
(2024)
Dual action tofacitinib-loaded PLGA nanoparticles alleviate colitis in an IBD mouse model.
Drug Delivery and Translational Research
, 15
pp. 2372-2389.
10.1007/s13346-024-01736-1.
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Abstract
Inflammatory bowel disease (IBD) affects over 7 million people worldwide and significant side effects are associated with current therapies such as tofacitinib citrate (TFC), which is linked to increased risks of malignancy and congestive heart issues. To mitigate these systemic adverse effects, localised drug delivery via nano-sized carriers to inflamed gut tissues represents a promising approach. Herein, we aimed to optimise the synthesis of nanoparticles (NPs) using a low molecular weight grade of Poly(lactic-co-glycolic acid) (PLGA) 50:50 loaded with TFC. This approach leverages the dual anti-inflammatory action of TFC and the local production of anti-inflammatory short-chain fatty acids from the degradation of PLGA by colonic gut microbiota. NPs were produced by nanoprecipitation and characterised for their drug release profile in vitro. The efficacy of the enhanced PLGA-TFC NPs was then tested in a C57BL/6 DSS colitis mouse model. The release profile of TFC from the enhanced PLGA NPs showed a 40% burst release within the first hour, followed by up to 80% drug release in the colonic environment. Notably, the degradation of PLGA by colonic gut microbiota did not significantly influence TFC release. In the mouse model, neither PLGA NPs alone nor TFC alone showed significant effects on weight loss compared to the TFC-loaded PLGA NPs, emphasising the enhanced efficacy potential of the combined formulation. Altogether, these results suggest a promising role of NP delivery systems in enhancing TFC efficacy, marking a significant step towards reducing dosage and associated side effects in IBD treatment. This study underscores the potential of PLGA-TFC NPs in providing targeted and effective therapy for IBD. Graphical Abstract: (Figure presented.)
| Type: | Article |
|---|---|
| Title: | Dual action tofacitinib-loaded PLGA nanoparticles alleviate colitis in an IBD mouse model |
| Location: | United States |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1007/s13346-024-01736-1 |
| Publisher version: | https://doi.org/10.1007/s13346-024-01736-1 |
| Language: | English |
| Additional information: | This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > UCL School of Pharmacy UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > UCL School of Pharmacy > Pharmaceutics |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10209809 |
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