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

Authors

Erika T. McCormick, George Washington University Department of Dermatology, George Washington University School of Medicine and Health Sciences, Washington, DC, USA.
Andrew Draganski, Zylö Therapeutics, Greenville, South Carolina, USA.
Samantha Chalmers, Division of Rheumatology, Department of Microbiology and Immunology, Albert Einstein College of Medicine, New York, Bronx, USA.
Joseph Zahn, George Washington University Department of Dermatology, George Washington University School of Medicine and Health Sciences, Washington, DC, USA.
Sayra Garcia, Division of Rheumatology, Department of Microbiology and Immunology, Albert Einstein College of Medicine, New York, Bronx, USA.
Dillon Nussbaum, George Washington University Department of Dermatology, George Washington University School of Medicine and Health Sciences, Washington, DC, USA.
Adam Friedman, George Washington University Department of Dermatology, George Washington University School of Medicine and Health Sciences, Washington, DC, USA.
Chaim Putterman, Division of Rheumatology, Department of Microbiology and Immunology, Albert Einstein College of Medicine, New York, Bronx, USA.
Joel Friedman, Division of Rheumatology, Department of Microbiology and Immunology, Albert Einstein College of Medicine, New York, Bronx, USA.

Document Type

Journal Article

Publication Date

9-19-2023

Journal

Experimental dermatology

DOI

10.1111/exd.14935

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

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.

APA Citation

McCormick, Erika T.; Draganski, Andrew; Chalmers, Samantha; Zahn, Joseph; Garcia, Sayra; Nussbaum, Dillon; Friedman, Adam; Putterman, Chaim; and Friedman, Joel, "Nano-encapsulated anandamide reduces inflammatory cytokines in vitro and lesion severity in a murine model of cutaneous lupus erythematosus" (2023). GW Authored Works. Paper 3378.
https://hsrc.himmelfarb.gwu.edu/gwhpubs/3378

Department

Dermatology