Title : Valproic acid encapsulated biodegradable microneedles for treatment of androgenetic alopecia
Abstract:
There are numerous genetic and environmental factors responsible for occurrence of male pattern hair loss known as androgenetic alopecia. Despite considerable medical advancements, the current treating agents, are limited by unsatisfactory cure rate and potential side effects. Valproic Acid, a well-kwon FDA approved anticonvulsant drug, was recently shown to induce hair follicle regrowth with a higher efficiency compared with current therapeutics including Minoxidil. Valproic acid activates several pathways including Wnt/β-catenin which is essential for hair growth. Although the exact action mechanism of valproic acid is not fully understood, previous studies suggested that application of valproic acid inhibits expression of glycogen synthase kinase 3β (GSK-3β), which upregulates β-catenin levels, leading to enhanced hair follicle transition from telogen (rest) to anagen (active) phase. Currently, topical application is the only available administration route of valproic acid to induce hair regrowth. Skin, as a protective barrier of body, however, limits the permeation efficiency of topically applied valproic acid. Thus, to improve its delivery efficiency, we encapsulated valproic acid within dissolving microneedles and applied them onto the skin by utilizing a micro-pillar based applicator. Dissolving microneedles are polymeric biodegradable micro dimensioned needles that encapsulate drugs and release them beneath the skin upon application in a minimally invasive manner. Carboxymethyl cellulose was used as backbone material of dissolving microneedles encapsulated with 50 μl of valproic acid. We found that by encapsulation of valproic acid within dissolving microneedles, the expression level of β-catenin, alkaline phosphatase, proliferating cell nuclear antigen, loricrin and hair follicle stem cell markers, including keratin 15, and CD34 that are responsible for hair growth were remarkably increased compared with the topical application.
Audience take away:
• An introduction to a novel drug delivery system, known as microneedle.
• Potential of dissolving microneedles in improving delivery efficiency of various sort of drugs, proteins, and vaccines.
• A new insight into androgenetic alopecia treatment technologies.
