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Development of an endocannabinoid microparticle formulation for the topical treatment of cutaneous manifestations of lupus erythematosus.

Award Information
Agency: Department of Health and Human Services
Branch: National Institutes of Health
Contract: 1R41AR082749-01
Agency Tracking Number: R41AR082749
Amount: $147,861.00
Phase: Phase I
Program: STTR
Solicitation Topic Code: NIAMS
Solicitation Number: PA22-178
Solicitation Year: 2022
Award Year: 2023
Award Start Date (Proposal Award Date): 2023-06-01
Award End Date (Contract End Date): 2025-05-31
Small Business Information
105A Ben Hamby Drive
Greenville, SC 29615
United States
DUNS: 080999429
HUBZone Owned: No
Woman Owned: No
Socially and Economically Disadvantaged: No
Principal Investigator
 (908) 420-4814
Business Contact
Phone: (858) 775-6710
Research Institution
United States

 Domestic Nonprofit Research Organization

Project Summary/Abstract
Approximately 500,000 people in the U.S. suffer from cutaneous lupus lesions (CLE), with a significant impact
on quality of life.4 Yet, there is no cure, the treatment options are limited, and no new drug has been FDA-
approved for over 50 years.84 As such, CLE represents a high unmet need for directed therapeutics.
Skin lesions are caused by a complex autoimmune response dependent on genetic and environmental factors.80
These lesions have common histological features such as interface dermatitis with interferon-regulated
chemokines expression.19 Anandamide (AEA) is a primary endocannabinoid involved in (i) modulation of the
innate and the adaptive immune system, (ii) processing of sensory input such as pruritus and pain, and (iii)
maintenance of skin barrier integrity.152,153 AEA’s primary pathway for decreasing inflammation is through binding
to CB2 receptors, which are predominantly expressed by macrophages and lymphocytes in peripheral organs
with immune function, including the skin.164 Preliminary data (i) demonstrate upregulation of CB2 receptors in
lesional human CLE tissue and (ii) show that AEA-treated peripheral blood mononuclear cells from CLE patients
produce lower levels of cytokines.
Given all this, AEA is a promising drug candidate for treatment of CLE. AEA faces a variety of delivery challenges,
however, including instability, limited penetration into the stratum corneum, and rapid metabolism by fatty acid
amide hydrolase (FAAH).134-135 To overcome these challenges, AEA was loaded into a novel topical silica-
derived particle delivery system that has been demonstrated to enhance bioavailability of several other APIs.
The resulting formulation (AEA-ZP) was shown to (i) enhance penetration of AEA into the stratum corneum, (ii)
provide extended release of AEA in the skin, and (iii) significantly reduce the size and severity of lupus lesions
in two murine lupus studies as compared to controls, including unencapsulated AEA.
During this Phase I proposal, the AEA-ZP prototype will be evaluated for efficacy in vivo in a new mouse model,
and preliminary toxicity data will be obtained. In vitro mechanism-of-action studies will be conducted using blood
and lesional tissue from human CLE patients; such data is expected to inform clinical development decisions
relating to target patient populations in which specific biomarker profiles might indicate patients that are more
likely to respond to treatment with AEA-ZP. In parallel, higher loaded AEA-ZP prototypes will be developed in
preparation for dose-ranging safety and efficacy studies to follow, and accelerated stability testing performed.

* Information listed above is at the time of submission. *

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