CoChat
Sign Up
Cited by 467Advanced Drug Delivery SystemsInflammatory Bowel DiseaseHydrogels: synthesis, properties, applications

An inflammation-targeting hydrogel for local drug delivery in inflammatory bowel disease

Open access
Zhang, Sufeng, Ermann, Joerg, Succi, Marc D., Zhou, Allen, Hamilton, Matthew J., Cao, Bonnie, Korzenik, Joshua R., Glickman, Jonathan N. +5 more·2015·Science Translational Medicine
DOI 10.1126/scitranslmed.aaa5657PMC PMC4825054
Open this paper in CoChat — free account

Abstract

A hydrogel binds to inflamed tissues, delivering therapeutics locally and reducing systemic drug exposure in mouse models of inflammatory bowel disease.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1126/scitranslmed.aaa5657

Cites

1 of 1 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • Treatment with ICMA noticeably reversed macrophage polarization from the M1 type to M2 type, an effect attributed to the anti-inflammatory properties of AP.

    “treatment with ICMA noticeably reversed the polarization of macrophages from the M1 type to M2 type. This effect may be attributed to the anti-inflammatory properties of AP (28, 42)”

    From Matrix mechanical remodeled carrier-free nanosystem for programmable closed-loop reversal of liver fibrosis via STING alkylation (2025) · cites this paper as [28]

    The Introduction identifies AP as the material used to make an inflammation-targeting drug-delivery hydrogel, not as an anti-inflammatory treatment. In Results (‘Drug delivery via IT-hydrogel enema improves therapeutic efficacy’), gel without drug did not significantly reduce colitis severity; the benefit was reported for dexamethasone-loaded gel. Our copy does not address ICMA-induced M1-to-M2 macrophage polarization or attribute such an effect to AP’s anti-inflammatory properties. (LLM, conf=0.77)

    Experimental — accuracy not yet measured

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

Flagged first, then by citations

Research works printed but not linked: 38

  1. [1]Loftus EV Jr Clinical epidemiology of inflammatory bowel disease: Incidence, prevalence, and environmental influences Gastroenterology 126 1504 1517 2004 15168363
  2. [2]Molodecky NA Soon IS Rabi DM Ghali WA Ferris M Chernoff G Benchimol EI Panaccione R Ghosh S Barkema HW Kaplan GG Increasing incidence and prevalence of the inflammatory bowel diseases with time, based on systematic review Gastroenterology 142 46 54.e42 2012 22001864
  3. [3]Hoivik ML Moum B Solberg IC Cvancarova M Hoie O Vatn MH Bernklev T IBSEN Study Group, Health-related quality of life in patients with ulcerative colitis after a 10-year disease course: Results from the IBSEN study Inflamm Bowel Dis 18 1540 1549 2012 21936030
  4. [4]Ghosh S Mitchell R Impact of inflammatory bowel disease on quality of life: Results of the European Federation of Crohn’s and Ulcerative Colitis Associations (EFCCA) patient survey J Crohns Colitis 1 10 20 2007 21172179
  5. [5]Kornbluth A Sachar DB Practice Parameters Committee of the American College of Gastroenterology, Ulcerative colitis practice guidelines in adults: American College of Gastroentero ogy, Practice Parameters Committee Am J Gastroenterol 105 501 523 2010 20068560
  6. [6]Ediger JP Walker JR Graff L Lix L Clara I Rawsthorne P Rogala L Miller N McPhail C Deering K Bernstein CN Predictors of medication adherence in inflammatory bowel disease Am J Gastroenterol 102 1417 1426 2007 17437505
  7. [7]Tirosh B Khatib N Barenholz Y Nissan A Rubinstein A Transferrin as a luminal target for negatively charged liposomes in the inflamed colonic mucosa Mol Pharm 6 1083 1091 2009 19603812
  8. [9]Monajemi H Meenan J Lamping R Obradov DO Radema SA Trown PW Tytgat GN Van Deventer SJ Inflammatory bowel disease is associated with increased mucosal levels of bactericidal/permeability-increasing protein Gastroenterology 110 733 739 1996 8608882
  9. [10]Ramasundara M Leach ST Lemberg DA Day AS Defensins and inflammation: The role of defensins in inflammatory bowel disease J Gastroenterol Hepatol 24 202 208 2009 19215333
  10. [11]Wehkamp J Fellermann K Herrlinger KR Baxmann S Schmidt K Schwind B Duchrow M Wohlschläger C Feller AC Stange EF Human β-defensin 2 but not β-defensin 1 is expressed preferentially in colonic mucosa of inflammatory bowel disease Eur J Gastroenterol Hepatol 14 745 752 2002 12169983
  11. [12]Jubeh TT Barenholz Y Rubinstein A Differential adhesion of normal and inflamed rat colonic mucosa by charged liposomes Pharm Res 21 447 453 2004 15070095
  12. [13]Jubeh TT Nadler-Milbauer M Barenholz Y Rubinstein A Local treatment of experimental colitis in the rat by negatively charged liposomes of catalase, TMN and SOD J Drug Target 14 155 163 2006 16753829
  13. [14]Wiener E Levanon D Macrophage cultures: An extracellular esterase Science 159 217 1968 5634918
  14. [15]Sorokin L The impact of the extracellular matrix on inflammation Nat Rev Immunol 10 712 723 2010 20865019
  15. [16]Lutolf MP Lauer-Fields JL Schmoekel HG Metters AT Weber FE Fields GB Hubbell JA Synthetic matrix metalloproteinase-sensitive hydrogels for the conduction of tissue regeneration: Engineering cell-invasion characteristics Proc Natl Acad Sci USA 100 5413 5418 2003 12686696 PMC154359
  16. [17]Patterson J Hubbell JA Enhanced proteolytic degradation of molecularly engineered PEG hydrogels in response to MMP-1 and MMP-2 Biomaterials 31 7836 7845 2010 20667588
  17. [18]Vemula PK Boilard E Syed A Campbell NR Muluneh M Weitz DA Lee DM Karp JM On-demand drug delivery from self-assembled nanofibrous gels: A new approach for treatment of proteolytic disease J Biomed Mater Res A 97 103 110 2011 21404422
  18. [19]Garrett WS Lord GM Punit S Lugo-Villarino G Mazmanian SK Ito S Glickman JN Glimcher LH Communicable ulcerative colitis induced by T-bet deficiency in the innate immune system Cell 131 33 45 2007 17923086 PMC2169385
  19. [20]van Meeteren ME Meijssen MA Zijlstra FJ The effect of dexamethasone treatment on murine colitis. Scand J Gastroenterol 35 517 521 2000 10868455
  20. [21]Kojouharoff G Hans W Obermeier F Männel DN Andus T Schölmerich J Gross V Falk W Neutralization of tumour necrosis factor (TNF) but not of IL-1 reduces inflammation in chronic dextran sulphate sodium-induced colitis in mice Clin Exp Immunol 107 353 358 1997 9030875 PMC1904573
  21. [22]Yuan H Ji WS Wu KX Jiao JX Sun LH Feng YT Anti-inflammatory effect of Diammonium Glycyrrhizinate in a rat model of ulcerative colitis World J Gastroenterol 12 4578 4581 2006 16874877 PMC4125652
  22. [23]Cannarile L Cuzzocrea S Santucci L Agostini M Mazzon E Esposito E Muià C Coppo M Di Paola R Riccardi C Glucocorticoid-induced leucine zipper is protective in Th1-mediated models of colitis Gastroenterology 136 530 541 2009 18996377
  23. [24]Ermann J Staton T Glickman JN de Waal Malefyt R Glimcher LH Nod/Ripk2 signaling in dendritic cells activates IL-17A–secreting innate lymphoid cells and drives colitis in T-bet−/−Rag2−/− (TRUC) mice Proc Natl Acad Sci USA 111 E2559 E2566 2014 24927559 PMC4078823
  24. [25]Dahan A Amidon GL Zimmermann EM Drug targeting strategies for the treatment of inflammatory bowel disease: A mechanistic update Expert Rev Clin Immunol 6 543 550 2010 20594127
  25. [26]Lamprecht A Ubrich N Yamamoto H Schäfer U Takeuchi H Maincent P Kawashima Y Lehr CM Biodegradable nanoparticles for targeted drug delivery in treatment of inflammatory bowel disease J Pharmacol Exp Ther 299 775 781 2001 11602694
  26. [27]Wilson DS Dalmasso G Wang L Sitaraman SV Merlin D Murthy N Orally delivered thioketal nanoparticles loaded with TNF-α–siRNA target inflammation and inhibit gene expression in the intestines Nat Mater 9 923 928 2010 20935658 PMC3142359
  27. [28]Sakhalkar HS Dalal MK Salem AK Ansari R Fu J Kiani MF Kurjiaka DT Hanes J Shakesheff KM Goetz DJ Leukocyte-inspired biodegradable particles that selectively and avidly adhere to inflamed endothelium in vitro and in vivo Proc Natl Acad Sci USA 100 15895 15900 2003 14668435 PMC307664
  28. [29]Sakhalkar HS Hanes J Fu J Benavides U Malgor R Borruso CL Kohn LD Kurjiaka DT Goetz DJ Enhanced adhesion of ligand-conjugated biodegradable particles to colitic venules FASEB J 19 792 794 2005 15764649
  29. [31]Gajanayake T Olariu R Leclère FM Dhayani A Yang Z Bongoni AK Banz Y Constantinescu MA Karp JM Vemula PK Rieben R Vögelin E A single localized dose of enzyme-responsive hydrogel improves long-term survival of a vascularized composite allograft Sci Transl Med 6 249ra110 2014 25122638
  30. [32]Stahn C Löwenberg M Hommes DW Buttgereit F Molecular mechanisms of glucocorticoid action and selective glucocorticoid receptor agonists Mol Cell Endocrinol 275 71 78 2007 17630118
  31. [33]Tsurufuji S Sugio K Takemasa F The role of glucocorticoid receptor and gene expression in the anti-inflammatory action of dexamethasone Nature 280 408 410 1979 460415
  32. [34]Harel E Rubinstein A Nissan A Khazanov E Milbauer MNadler Barenholz Y Tirosh B Enhanced transferrin receptor expression by proinflammatory cytokines in enterocytes as a means for local delivery of drugs to inflamed gut mucosa PLOS One 6 e24202 2011 21915296 PMC3167832
  33. [35]Li F Hui DY Modified low density lipoprotein enhances the secretion of bile salt-stimulated cholesterol esterase by human monocyte-macrophages. Species-specific difference in macrophage cholesteryl ester hydrolase J Biol Chem 272 28666 28671 1997 9353334
  34. [36]Lu X Howard MD Mazik M Eldridge J Rinehart JJ Jay M Leggas M Nanoparticles containing anti-inflammatory agents as chemotherapy adjuvants: Optimization and in vitro characterization AAPS J 10 133 140 2008 18446513 PMC2751458
  35. [37]Higai K Ichikawa A Matsumoto K Binding of sialyl Lewis X antigen to lectin-like receptors on NK cells induces cytotoxicity and tyrosine phosphorylation of a 17-kDa protein. Biochim Biophys Acta 1760 1355 1363 2006 16842926
  36. [38]Svensson O Thuresson K Arnebrant T Interactions between chitosan-modified particles and mucin-coated surfaces J Colloid Interface Sci 325 346 350 2008 18597767
  37. [40]Yan Y Kolachala V Dalmasso G Nguyen H Laroui H Sitaraman SV Merlin D Temporal and spatial analysis of clinical and molecular parameters in dextran sodium sulfate induced colitis PLOS One 4 e6073 2009 19562033 PMC2698136
  38. [41]Bradley PP Priebat DA Christensen RD Rothstein G Measurement of cutaneous inflammation: Estimation of neutrophil content with an enzyme marker J Invest Dermatol 78 206 209 1982 6276474

Cited by

Sorted by citations

Authors
Zhang, S., Ermann, J., Succi, M. D., Zhou, A., Hamilton, M. J., Cao, B., Korzenik, J. R., Glickman, J. N., Vemula, P. K., Glimcher, L. H., Traverso, G., Langer, R., & Karp, J. M.
Affiliations
  • Brigham and Women's Hospital (US)
  • Harvard University (US)
  • Institute for Stem Cell Biology and Regenerative Medicine (IN)
  • Weill Cornell Medicine (US)
  • The David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Corresponding author
  • Zhang, Sufeng
  • Ermann, Joerg
  • Traverso, Giovanni
  • Karp, Jeffrey M.
ORCID
Venue
Science Translational Medicine
Publisher
American Association for the Advancement of Science (AAAS)
Published
2015-08-12
Volume
7
Issue
300
Pages
300ra128-300ra128
ISSN
  • 1946-6234 (ISSN-L)
  • 1946-6242
DOI
10.1126/scitranslmed.aaa5657
PMC
PMC4825054
OpenAlex
W2257473733
Cited by
467
References
1
Citations by year
2026: 53 · 2025: 65 · 2024: 56 · 2023: 49 · 2022: 53 · 2021: 51 · 2020: 46 · 2019: 36 · 2018: 26 · 2017: 17 · 2016: 13 · 2015: 2
FWCI
10.71
Type
journal article
Language
en
Open access
Licence
www.sciencemag.org/about/science-licenses-journal-article-reuse (vor, 366 d)
Locations
  • Science Translational Medicine (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
  • Digital Access to Scholarship at Harvard (DASH) (Harvard University) (acceptedVersion)
  • DSpace@MIT (Massachusetts Institute of Technology) (submittedVersion, cc-by-nc)
  • PMC
Funders
  • NIH (CA112663, T32DK7191-38-S1, DE013023, EB000244, DE023432, AR063866)
  • Alexander von Humboldt Foundation
  • Harvard Institute of Translational Immunology/Helmsley Trust Pilot
Topics
  • Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmaceutical Science › Advanced Drug Delivery Systems
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Inflammatory Bowel Disease
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Medicine › Hydrogels: synthesis, properties, applications
Keywords
local drug delivery, inflammatory bowel disease, Crohn's disease, ulcerative colitis, ascorbyl palmitate, hydrogel microfibers, dexamethasone, colonic inflammation, mouse colitis model
MeSH terms
Animals, Biopsy, Colitis, Colon, Dexamethasone, Humans, Inflammation, Intestinal Mucosa, Macrophages, Mice, Inbred BALB C, Inflammatory Bowel Diseases, Drug Delivery Systems, Treatment Outcome, Hydrogel, Polyethylene Glycol Dimethacrylate

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review