Leveraging thiol-functionalized biomucoadhesive hybrid nanoliposome for local therapy of ulcerative colitis.

Autor: Kanika; Chemical Biology Unit, Institute of Nano Science and Technology, Sector 81, Knowledge City, Sahibzada Ajit Singh Nagar, Mohali, Punjab, 140306, India., Ahmad A; Julia McFarlane Diabetes Research Centre (JMDRC) and Department of Microbiology, Immunology and Infectious Diseases, Snyder Institute for Chronic Diseases and Hotchkiss Brain Institute, Cumming School of Medicine, University of Calgary, Calgary, Alberta, T2N4N1, Canada., Kumar A; Chemical Biology Unit, Institute of Nano Science and Technology, Sector 81, Knowledge City, Sahibzada Ajit Singh Nagar, Mohali, Punjab, 140306, India., Rahul; Department of Chemistry, Malaviya National Institute of Technology, Jaipur, Rajasthan, 302017, India., Mishra RK; Department of Pharmaceutical Sciences, School of Health Sciences and Technology, UPES, Dehradun, India., Ali N; Department of Pharmacology & Toxicology, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh, 11451, Saudi Arabia., Navik U; Department of Pharmacology, Central University of Punjab, Bathinda, Ghudda, Punjab, 151401, India., Parvez S; Department of Toxicology, School of Chemical & Life Sciences, Jamia Hamdard, New Delhi, 110062, India., Khan R; Chemical Biology Unit, Institute of Nano Science and Technology, Sector 81, Knowledge City, Sahibzada Ajit Singh Nagar, Mohali, Punjab, 140306, India. Electronic address: rehankhan@inst.ac.in.
Jazyk: angličtina
Zdroj: Biomaterials [Biomaterials] 2025 Jan; Vol. 312, pp. 122747. Date of Electronic Publication: 2024 Aug 06.
DOI: 10.1016/j.biomaterials.2024.122747
Abstrakt: Directly administering medication to inflamed intestinal sites for treating ulcerative colitis (UC), poses significant challenges like retention time, absorption variability, side effects, drug stability, and non-specific delivery. Recent advancements in therapy to treat colitis aim to improve local drug availability that is enema therapy at the site of inflammation, thereby reducing systemic adverse effects. Nevertheless, a key limitation lies in enemas' inability to sustain medication in the colon due to rapid peristaltic movement, diarrhea, and poor local adherence. Therefore, in this work, we have developed site-specific thiolated mucoadhesive anionic nanoliposomes to overcome the limitations of conventional enema therapy. The thiolated delivery system allows prolonged residence of the delivery system at the inflamed site in the colon, confirmed by the adhesion potential of thiolated nanoliposomes using in-vitro and in-vivo models. To further provide therapeutic efficacy thiolated nanoliposomes were loaded with gallic acid (GA), a natural compound known for its antibacterial, antioxidant, and potent anti-inflammatory properties. Consequently, Gallic Acid-loaded Thiolated 2,6 DALP DMPG (GATh@APDL) demonstrates the potential for targeted adhesion to the inflamed colon, facilitated by their small size 100 nm and anionic nature. Therapeutic studies indicate that this formulation offers protective effects by mitigating colonic inflammation, downregulating the expression of NF-κB, HIF-1α, and MMP-9, and demonstrating superior efficacy compared to the free GA enema. The encapsulated GA inhibits the NF-κB expression, leading to enhanced expression of MUC2 protein, thereby promoting mucosal healing in the colon. Furthermore, GATh@APDL effectively reduces neutrophil infiltration and regulates immune cell quantification in colonic lamina propria. Our findings suggest that GATh@APDL holds promise for alleviating UC and addressing the limitations of conventional enema therapy.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 Elsevier Ltd. All rights reserved.)
Databáze: MEDLINE
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