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Isosorbide Di-(Linoleate/Oleate) Stimulates Prodifferentiation Gene Expression to Restore the Epidermal Barrier and Improve Skin Hydration.

Authors
  • Bojanowski, Krzysztof1
  • Swindell, William R2
  • Cantor, Shyla3
  • Chaudhuri, Ratan K4
  • 1 Sunny BioDiscovery, Santa Paula, California, USA; Symbionyx Pharmaceuticals, Boonton, New Jersey, USA. , (Jersey)
  • 2 Department of Internal Medicine, The Jewish Hospital, Cincinnati, Ohio, USA. Electronic address: [email protected]
  • 3 Cantor Research Laboratories, Blauvelt, New York, USA.
  • 4 Symbionyx Pharmaceuticals, Boonton, New Jersey, USA; Sytheon, Boonton, New Jersey, USA. , (Jersey)
Type
Published Article
Journal
Journal of Investigative Dermatology
Publisher
Elsevier
Publication Date
Jun 01, 2021
Volume
141
Issue
6
Identifiers
DOI: 10.1016/j.jid.2020.09.029
PMID: 33181142
Source
Medline
Language
English
License
Unknown

Abstract

The breakdown of the epidermal barrier and consequent loss of skin hydration is a feature of skin aging and eczematous dermatitis. Few treatments, however, resolve these underlying processes to provide full symptomatic relief. In this study, we evaluated isosorbide di-(linoleate/oleate) (IDL), which was generated by esterifying isosorbide with sunflower fatty acids. Topical effects of IDL in skin were compared with those of ethyl linoleate/oleate, which has previously been shown to improve skin barrier function. Both IDL and ethyl linoleate/oleate downregulated inflammatory gene expression, but IDL more effectively upregulated the expression of genes associated with keratinocyte differentiation (e.g., KRT1, GRHL2, SPRR4). Consistent with this, IDL increased the abundance of epidermal barrier proteins (FLG and involucrin) and prevented cytokine-mediated stratum corneum degradation. IDL also downregulated the expression of unhealthy skin signature genes linked to the loss of epidermal homeostasis and uniquely repressed an IFN-inducible coexpression module activated in multiple skin diseases, including psoriasis. In a double-blind, placebo-controlled trial enrolling females with dry skin, 2% IDL lotion applied over 2 weeks significantly improved skin hydration and decreased transepidermal water loss (NCT04253704). These results demonstrate mechanisms by which IDL improves skin hydration and epidermal barrier function, supporting IDL as an effective intervention for the treatment of xerotic pruritic skin. Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.

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