Development and optimization of the Glabridin-loaded dissolving microneedle for enhanced treatment of keloid

Abstract

Glabridin (Gla) has been reported to have significant effects in scar treatment, and however, the water insolubility of Gla leads to its poor transdermal absorption ability, which affects its bioactivities. Therefore, we attempted to prepare the Gla dissolving microneedles (Gla-MN) to improve the absorbtion of Gla. After investigation of the 3 factors including the needle tip matrix concentration, the prescription concentration of backing material, and the dissolution method of Gla, we finally determined the process parameters of 10% hyaluronic acid (HA) as the needle tip and 5% polyvinyl alcohol (PVA) as the backing, according to which the Gla-MN was prepared with the good characteristics of high hardness, complete appearance and good in vitro dissolution ability. We then loaded Gla onto the microneedles and measured that the average drug loading of Gla-MN was 2.26 ± 0.11 μg/mg and the cumulative transdermal release of Gla-MN was up to 76.9% after 24 h. In addition, Gla-MN had good skin penetration properties, with Gla-MN penetrating at least 4 to 5 layers of parafilm. And the skin basically could return to normal after 4 h of piercing. Importantly, our results showed that Gla-MN had higher transdermal delivery and therapeutic effects against keloid than that of Gla at the same dosage.

Keywords

• Dissolving microneedle
• Glabridin
• Keloid
• Transdermal absorption
• PI3K/Akt signaling
• TGF-β1/α-SMA