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Topical Delivery of Atraric Acid Derived from Stereocaulon japonicum with Enhanced Skin Permeation and Hair Regrowth Activity for Androgenic Alopecia.

ABSTRACT: Atraric acid (AA) is a phenolic compound isolated from Stereocaulon japonicum that has demonstrated anti-androgen properties and was used to design an alternative formulation for the treatment of alopecia. This new topical formulation was designed using a solvent mixture system composed of ethanol as a volatile vehicle, oleic acid as a permeation enhancer, and water for skin hydration. The ideal topical AA formulation (AA-TF#15) exhibited an 8.77-fold higher human skin flux and a 570% increase in dermal drug deposition, compared to 1% (w/w) AA in ethanol. In addition, compared to other formulations, AA-TF#15 (1% [w/w] AA) activated keratinocytes and human dermal papilla cell proliferation at a concentration of 50 µM AA, which is equivalent to 50 µM minoxidil. Moreover, AA-TF#15 treatment produced a significant increase in hair regrowth by 58.0% and 41.9% compared to the 1% (w/w) minoxidil and oral finasteride (1 mg/kg)-treated mice. In addition, AA-TF#15 showed a higher expression level of aldehyde dehydrogenase 1, β-catenin, cyclin D1, and pyruvate kinase M2 proteins in the skin of AA-TF#15-treated mice compared to that of those treated with minoxidil and oral finasteride. These findings suggest AA-TF#15 is an effective formulation for the treatment of scalp androgenic alopecia.

SUBMITTER: Pulat S

PROVIDER: S-EPMC9960134 | biostudies-literature | 2023 Jan

REPOSITORIES: biostudies-literature

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Topical Delivery of Atraric Acid Derived from <i>Stereocaulon japonicum</i> with Enhanced Skin Permeation and Hair Regrowth Activity for Androgenic Alopecia.

Pulat Sultan S Subedi Laxman L Pandey Prashant P Bhosle Suresh R SR Hur Jae-Seoun JS Shim Jung-Hyun JH Cho Seung-Sik SS Kim Ki-Taek KT Ha Hyung-Ho HH Kim Hangun H Park Jin Woo JW

Pharmaceutics 20230119 2

Atraric acid (AA) is a phenolic compound isolated from <i>Stereocaulon japonicum</i> that has demonstrated anti-androgen properties and was used to design an alternative formulation for the treatment of alopecia. This new topical formulation was designed using a solvent mixture system composed of ethanol as a volatile vehicle, oleic acid as a permeation enhancer, and water for skin hydration. The ideal topical AA formulation (AA-TF#15) exhibited an 8.77-fold higher human skin flux and a 570% inc ...[more]

PMID: 36839662

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Project description:BackgroundAlopecia areata (AA) is one of the most common autoimmune diseases and targets the hair follicles, with high impact on the quality of life and self-esteem of patients due to hair loss. Clinical management and outcomes are challenged by current limited immunosuppressive and immunomodulating regimens.MethodsWe have developed a Stem Cell Educator therapy in which a patient's blood is circulated through a closed-loop system that separates mononuclear cells from the whole blood, allows the cells to briefly interact with adherent human cord blood-derived multipotent stem cells (CB-SC), and returns the "educated" autologous cells to the patient's circulation. In an open-label, phase 1/phase 2 study, patients (N = 9) with severe AA received one treatment with the Stem Cell Educator therapy. The median age was 20 years (median alopecic duration, 5 years).ResultsClinical data demonstrated that patients with severe AA achieved improved hair regrowth and quality of life after receiving Stem Cell Educator therapy. Flow cytometry revealed the up-regulation of Th2 cytokines and restoration of balancing Th1/Th2/Th3 cytokine production in the peripheral blood of AA subjects. Immunohistochemistry indicated the formation of a "ring of transforming growth factor beta 1 (TGF-β1)" around the hair follicles, leading to the restoration of immune privilege of hair follicles and the protection of newly generated hair follicles against autoimmune destruction. Mechanistic studies revealed that co-culture with CB-SC may up-regulate the expression of coinhibitory molecules B and T lymphocyte attenuator (BTLA) and programmed death-1 receptor (PD-1) on CD8β(+)NKG2D(+) effector T cells and suppress their proliferation via herpesvirus entry mediator (HVEM) ligands and programmed death-1 ligand (PD-L1) on CB-SCs.ConclusionsCurrent clinical data demonstrated the safety and efficacy of the Stem Cell Educator therapy for the treatment of AA. This innovative approach produced lasting improvement in hair regrowth in subjects with moderate or severe AA.Trial registrationClinicalTrials.gov, NCT01673789, 21 August 2012.

Project description:ImportanceContact immunotherapy with diphenylcyclopropenone or squaric acid dibutyl ester is a preferred treatment for severe alopecia areata; however, the defined criteria for therapeutic hair regrowth and regrowth rate have been highly heterogeneous across studies.ObjectiveTo summarize the clinical outcomes of contact immunotherapy for alopecia areata according to standardized criteria for therapeutic hair regrowth and several prognostic factors.Data sourceA database search of MEDLINE, Embase, and Cochrane Library was performed for articles published before November 20, 2017, using the search terms areata, totalis, universalis, sensitizer, sensitization, immunotherapy, DPCP, diphenylcyclopropenone, diphencyprone, SADBE, and squaric.Study selectionClinical trials or observational studies that investigated contact immunotherapy for alopecia areata and subgrouped the disease into patchy alopecia or alopecia totalis/universalis and reported their hair regrowth rates were included, whereas studies that investigated combination therapy or nonconventional protocol and case series or reviews were excluded.Data extraction and synthesisThe following data were extracted from each of the studies included in this meta-analysis: study year and setting, sensitizer type, study population, study population composition by disease subtype, defined criteria for therapeutic hair regrowth, and regrowth rate of contact immunotherapy. The incidence of adverse effects and recurrence rate were also recorded. A random effects model was used for data synthesis because of the expected high heterogeneity of the included studies.Main outcomes and measuresThe main outcome was therapeutic hair regrowth rate according to the 4-grade criteria for therapeutic regrowth. Secondary outcomes included incidence of treatment-related adverse effects and recurrence rate.ResultsForty-five studies comprising 2227 patients were analyzed. The overall rate of any hair regrowth was 65.5% among patients with alopecia areata (74.6% in the patchy alopecia and 54.5% in the alopecia totalis/universalis subgroups). However, the complete regrowth rate was 32.3% (24.9% in the patchy alopecia and 32.3% in the alopecia totalis/universalis subgroups). Disease extent of 50% or greater (odds ratio [OR], 3.05; 95% CI, 2.26-4.12), atopic history (OR, 1.61; 95% CI, 1.03-2.50), and nail involvement (OR, 2.06; 95% CI. 1.26-3.36) were associated with poorer therapeutic outcome. Recurrence rates were 38.3% among patients receiving maintenance treatment and 49.0% among those not receiving maintenance treatment.Conclusions and relevanceVarious factors were associated with the clinical outcomes of contact immunotherapy for alopecia areata, with significant differences in hair regrowth rates according to the level of expected therapeutic regrowth. Quantitative summarization may improve patient education and lead to better therapeutic adherence and outcomes.

Dataset Information

Topical Delivery of Atraric Acid Derived from Stereocaulon japonicum with Enhanced Skin Permeation and Hair Regrowth Activity for Androgenic Alopecia.

Publications

Topical Delivery of Atraric Acid Derived from <i>Stereocaulon japonicum</i> with Enhanced Skin Permeation and Hair Regrowth Activity for Androgenic Alopecia.

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