Magnetically Powered Chitosan Milliwheels for Rapid Translation, Barrier Function Rescue, and Delivery of Therapeutic Proteins to the Inflamed Gut Epithelium.

Autor:	Osmond MJ; Department of Bioengineering, University of Colorado Denver, Anschutz Medical Campus, Aurora, Colorado 80045, United States.; Department of Chemical and Biological Engineering, Colorado School of Mines, Golden, Colorado 80401, United States., Korthals E; Department of Bioengineering, University of Colorado Denver, Anschutz Medical Campus, Aurora, Colorado 80045, United States., Zimmermann CJ; Department of Chemical and Biological Engineering, Colorado School of Mines, Golden, Colorado 80401, United States., Roth EJ; Department of Bioengineering, University of Colorado Denver, Anschutz Medical Campus, Aurora, Colorado 80045, United States., Marr DWM; Department of Chemical and Biological Engineering, Colorado School of Mines, Golden, Colorado 80401, United States., Neeves KB; Department of Bioengineering, University of Colorado Denver, Anschutz Medical Campus, Aurora, Colorado 80045, United States.; Department of Pediatrics, Section of Hematology, Oncology, and Bone Marrow Transplant, University of Colorado Denver, Anschutz Medical Campus, Aurora, Colorado 80045, United States.
Jazyk:	angličtina
Zdroj:	ACS omega [ACS Omega] 2023 Mar 16; Vol. 8 (12), pp. 11614-11622. Date of Electronic Publication: 2023 Mar 16 (Print Publication: 2023).
DOI:	10.1021/acsomega.3c00886
Abstrakt:	Inflammatory bowel disease (IBD) is mediated by an overexpression of tumor necrosis factor-α (TNF) by mononuclear cells in the intestinal mucosa. Intravenous delivery of neutralizing anti-TNF antibodies can cause systemic immunosuppression, and up to one-third of people are non-responsive to treatment. Oral delivery of anti-TNF could reduce adverse effects; however, it is hampered by antibody degradation in the harsh gut environment during transit and poor bioavailability. To overcome these shortcomings, we demonstrate magnetically powered hydrogel particles that roll along mucosal surfaces, provide protection from degradation, and sustain the local release of anti-TNF. Iron oxide particles are embedded into a cross-linked chitosan hydrogel and sieved to produce 100-200 μm particles called milliwheels (m-wheels). Once loaded with anti-TNF, these m-wheels release 10 to 80% of their payload over 1 week at a rate that depends on the cross-linking density and pH. A rotating magnetic field induces a torque on the m-wheels that results in rolling velocities greater than 500 μm/s on glass and mucus-secreting cells. The permeability of the TNF-challenged gut epithelial cell monolayers was rescued in the presence of anti-TNF carrying m-wheels, which both neutralized the TNF and created an impermeable patch over leaky cell junctions. With the ability to translate over mucosal surfaces at high speed, provide sustained release directly to the inflamed epithelium, and provide barrier rescue, m-wheels demonstrate a potential strategy to deliver therapeutic proteins for the treatment of IBD. Competing Interests: The authors declare no competing financial interest. (© 2023 The Authors. Published by American Chemical Society.)
Databáze:	MEDLINE
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