Nano-encapsulated anandamide reduces inflammatory cytokines in vitro and lesion severity in a murine model of cutaneous lupus erythematosus

Erika T. McCormick, Andrew Draganski, Samantha Chalmers, Joseph Zahn, Sayra Garcia, Dillon Nussbaum, Adam Friedman, Chaim Putterman, Joel Friedman

Research output: Contribution to journalArticlepeer-review

Abstract

Cutaneous lupus erythematosus (CLE) is a heterogeneous autoimmune skin disease which occurs independently and in conjunction with systemic lupus erythematosus. Drug development for CLE is severely lacking. Anandamide (AEA) is a primary endocannabinoid which exhibits immunomodulatory effects through mixed cannabinoid receptor agonism. We evaluated AEA as topical treatment for CLE and assessed benefits of nanoparticle encapsulation (AEA-NP) on cutaneous drug penetration, delivery and biological activity. Compared to untreated controls, AEA-NP decreased IL-6 and MCP-1 in UVB-stimulated keratinocytes (p < 0.05) in vitro. In BALB/c mice, AEA-NP displayed improved cutaneous penetration, extended release and persistence of AEA in the follicular unit extending to the base after 24 h. Utilizing the MRL-lpr lupus murine model, twice weekly treatment of lesions with topical AEA-NP for 10 weeks led to decreased clinical and histologic lesion scores compared to unencapsulated AEA and untreated controls (p < 0.05). Prophylactic application of AEA-NP to commonly involved areas on MRL-lpr mice similarly resulted in decreased clinical and histologic scores when compared to controls (p < 0.05), and reduced C3 and IBA-1 in lesional tissue (p < 0.05). The demonstrated clinical and immunomodulatory effects of treatment with AEA support its potential as therapy for CLE. This work also suggests that encapsulation of AEA improves penetration and treatment efficacy. Future studies will be conducted to assess full therapeutic potential.

Original languageEnglish
Pages (from-to)2072-2083
Number of pages12
JournalExperimental Dermatology
Volume32
Issue number12
DOIs
StatePublished - Dec 2023

Bibliographical note

Publisher Copyright:
© 2023 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Keywords

  • AEA
  • CLE
  • IBA-1
  • IL-27
  • IL-6
  • MCP-1
  • MRL/lpr mice
  • MRL/lpr model
  • PAM212
  • anandamide
  • cannabinoids
  • complement C3 protein
  • cutaneous lupus erythematosus
  • mixed cannabinoid agonism
  • murine CLE
  • murine lupus
  • nano-encapsulated
  • nano-encapsulated anandamide
  • nano-encapsulated cannabinoids
  • nano-encapsulation
  • nanoparticle encapsulation
  • nanoparticle-encapsulated AEA
  • nanoparticles
  • topical AEA
  • topical anandamide
  • topical cannabinoid

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