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Kesserwan S, Mao L, Sharafieh R, et al. A pharmacological approach assessing the role of mast cells in insulin infusion site inflammation. Drug Deliv Transl Res. 2021;doi: 10.1007/s13346-021-01070-w.
Kesserwan, S., Mao, L., Sharafieh, R., Kreutzer, D. L., & Klueh, U. (2021). A pharmacological approach assessing the role of mast cells in insulin infusion site inflammation. Drug delivery and translational research, . https://doi.org/10.1007/s13346-021-01070-w
Kesserwan, Shereen, et al. "A pharmacological approach assessing the role of mast cells in insulin infusion site inflammation." Drug delivery and translational research vol. (2021). doi: https://doi.org/10.1007/s13346-021-01070-w
Kesserwan S, Mao L, Sharafieh R, Kreutzer DL, Klueh U. A pharmacological approach assessing the role of mast cells in insulin infusion site inflammation. Drug Deliv Transl Res. 2021 Sep 24; doi: 10.1007/s13346-021-01070-w. Epub 2021 Sep 24. PMID: 34561836.
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Drug Deliv Transl Res. 2021 Sep 24; doi: 10.1007/s13346-021-01070-w. Epub 2021 Sep 24.

A pharmacological approach assessing the role of mast cells in insulin infusion site inflammation.

Drug delivery and translational research

Shereen Kesserwan, Li Mao, Roshanak Sharafieh, Donald L Kreutzer, Ulrike Klueh

Affiliations

  1. Department of Biomedical Engineering, Integrative Biosciences Center, Wayne State University, Detroit, MI, USA.
  2. Department of Surgery, School of Medicine, University of Connecticut, Farmington, CT, USA.
  3. Department of Biomedical Engineering, Integrative Biosciences Center, Wayne State University, Detroit, MI, USA. [email protected].

PMID: 34561836 DOI: 10.1007/s13346-021-01070-w

Abstract

Background Extending the lifespan of subcutaneous insulin administration sets and infusion pumps requires overcoming unreliable insulin delivery induced by dermal reactions. All commercially available insulin formulations contain insulin phenolic preservatives (IPP), which stabilize the insulin molecule but result in unwanted cell and tissue toxicity. Mast cells, which are the first line of defense once the epithelium is breached, are particularly abundant beneath the skin surface. Thus, we hypothesize a sequence of events initiated by device insertion that activates skin mast cells (MC) that subsequently trigger neutrophil and monocyte/macrophage recruitment. The ensuing inflammatory response compromises effective insulin infusion therapy. Methods We employed a non-genetic, pharmacological approach to MC membrane stabilization using Cromolyn sodium (CS), which inhibits MC degranulation. These studies were conducted in our modified air pouch mouse model using non-diabetic and streptozotocin induced diabetic mice. We evaluated the impact of systemic CS through intraperitoneal injections, as well as the impact of local CS through co-infusion, on infusion catheter insertion and IPP-induced inflammation. Results CS at a concentration of 50 mg/kg minimized inflammation triggered in response to insulin phenolic preservatives present in standard insulin formulations. The resultant degree of tissue inflammation was comparable to that observed with saline injections. Conclusion Targeting MC has the potential to extend the longevity of insulin infusion sets by mitigating the inflammatory response. Future studies should be directed at employing other MC models, such as newer Cre/loxP mouse strains, to confirm the sentinel role of MC in insulin infusion therapy.

© 2021. Controlled Release Society.

Keywords: Continuous subcutaneous insulin infusion; Cromolyn sodium; Inflammation; Insulin infusion sets; Mast cells

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