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Enzyme- and pH-Responsive Microencapsulated Nanogels for Oral Delivery of siRNA to Induce TNF-α Knockdown in the Intestine

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Department of Chemical Engineering, C0400, The University of Texas at Austin, Austin, Texas 78712, United States
Department of Biomedical Engineering, C0800, The University of Texas at Austin, Austin, Texas 78712, United States
# Department of Surgery and Perioperative Care, Dell Medical School, The University of Texas at Austin, Austin, Texas 78712, United States
§ College of Pharmacy, A1900, The University of Texas at Austin, Austin, Texas 78712, United States
Institute for Biomaterials, Drug Delivery, and Regenerative Medicine, The University of Texas at Austin, Austin, Texas 78712, United States
*E-mail: [email protected]. Phone: (512) 471-6644.
Cite this: Biomacromolecules 2016, 17, 3, 788-797
Publication Date (Web):January 26, 2016
https://doi.org/10.1021/acs.biomac.5b01518
Copyright © 2016 American Chemical Society
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Abstract

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Inflammatory bowel diseases (IBD) manifest from excessive intestinal inflammation. Local delivery of siRNA that targets these inflammatory cytokines would provide a novel treatment approach. Microencapsulated nanogels are designed and validated as platforms for oral delivery of siRNA targeting TNF-α, a common clinical target of IBD treatments. The preferred platform was designed to (i) protect siRNA-loaded nanogels from the harsh acidic environment of the upper GI tract and (ii) enzymatically degrade and release the nanogels once the carrier has reached the intestinal region. This platform consists of microgels composed of poly(methacrylic acid-co-N-vinyl-2-pyrrolidone) (P[MAA-co-NVP]) cross-linked with a trypsin-degradable peptide linker. The P(MAA-co-NVP) backbone is designed to collapse around and protect encapsulated nanogel from degradation at the low pH levels seen in the stomach (pH 2–4). At pH levels of 6–7.5, as typically observed in the intestine, the P(MAA-co-NVP) matrix swells, potentially facilitating diffusion of intestinal fluid and degradation of the matrix by intestinal enzymes such as trypsin, thus “freeing” the therapeutic nanogels for delivery and cellular uptake within the intestine. TNF-α siRNA-loaded nanogels released from this platform were capable of inducing potent knockdown of secreted TNF-α levels in murine macrophages, further validating the potential for this approach to be used for the treatment of IBD.

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This material is available free of charge via the Internet at http://pubs.acs.org/ The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acs.biomac.5b01518.

  • Further discussion of nanogel encapsulation, microgel degradation, and secreted TNF-α levels (PDF)

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  10. Owen R. Griffiths, John Landon, Ruth E. Coxon, Keith Morris, Philip James, Rachel Adams. Inflammatory bowel disease and targeted oral anti-TNF α  therapy. 2020,,, 157-198. DOI: 10.1016/bs.apcsb.2019.08.009.
  11. Serena Bertoni, Ariella Machness, Mattia Tiboni, Raquel Bártolo, Hélder A. Santos. Reactive oxygen species responsive nanoplatforms as smart drug delivery systems for gastrointestinal tract targeting. Biopolymers 2020, 111 (1) DOI: 10.1002/bip.23336.
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  15. David Ulkoski, Annette Bak, John T. Wilson, Venkata R. Krishnamurthy. Recent advances in polymeric materials for the delivery of RNA therapeutics. Expert Opinion on Drug Delivery 2019, 16 (11) , 1149-1167. DOI: 10.1080/17425247.2019.1663822.
  16. Rachel Chevalier. si RNA Targeting and Treatment of Gastrointestinal Diseases. Clinical and Translational Science 2019, 12 (6) , 573-585. DOI: 10.1111/cts.12668.
  17. Matilde Durán‐Lobato, Zhigao Niu, María José Alonso. Oral Delivery of Biologics for Precision Medicine. Advanced Materials 2019, 30, 1901935. DOI: 10.1002/adma.201901935.
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  36. Lies A. L. Fliervoet, Johan F. J. Engbersen, Raymond M. Schiffelers, Wim E. Hennink, Tina Vermonden. Polymers and hydrogels for local nucleic acid delivery. Journal of Materials Chemistry B 2018, 6 (36) , 5651-5670. DOI: 10.1039/C8TB01795F.
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  38. Ying Zhang, Zhiping Zhou, Xinyuan Zhu, Mingsheng Chen. A smart gene delivery platform: Cationic oligomer. European Journal of Pharmaceutical Sciences 2017, 105, 33-40. DOI: 10.1016/j.ejps.2017.05.002.
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  42. David Julian McClements. Designing biopolymer microgels to encapsulate, protect and deliver bioactive components: Physicochemical aspects. Advances in Colloid and Interface Science 2017, 240, 31-59. DOI: 10.1016/j.cis.2016.12.005.
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  49. Yi Li, Feihu Wang, Honggang Cui. Peptide-based supramolecular hydrogels for delivery of biologics. Bioengineering & Translational Medicine 2016, 1 (3) , 306-322. DOI: 10.1002/btm2.10041.
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