Epigallocatechin Gallate/L-Ascorbic Acid-Loaded Poly-γ-Glutamate Microneedles with Antioxidant, Anti-inflammatory, and Immunomodulatory Effects for the Treatment of Atopic Dermatitis.

Epigallocatechin gallate (EGCG) is a potential therapeutic agent for treatment of atopic dermatitis (AD) due to its antioxidant and anti-inflammatory activities. However, inherent instability of EGCG greatly limits its bioavailability and clinical efficacy. In this study, we developed a poly-γ-glutamate (γ-PGA)-based microneedle (MN) formulation capable of maintaining EGCG's stability and efficiently delivering EGCG into the skin to ameliorate AD symptoms. The γ-PGA MN can not only protect EGCG from oxidation, but also serve as an immunomodulator to downregulate T helper type 2 (Th2)-type immune responses. Encapsulation of EGCG into the γ-PGA MN and utilization of L-ascorbic acid (AA) as a stabilizer preserved 95% of its structural stability and retained 93% of its initial antioxidant activity after 4 weeks of storage. Once-weekly administration of EGCG/AA-loaded MNs to an Nc/Nga mouse model of AD for 4 weeks significantly ameliorated skin lesions and epidermal hyperplasia by reducing serum IgE (from 12156 ± 1344 to 5555 ± 1362  ng/mL) and histamine levels (from 81 ± 18 to 40 ± 5 pg/mL) and inhibiting IFN-γ (from 0.10 ± 0.01 to 0.01 pg/mg total protein) and Th2-type cytokine production, when compared to the AD (no treatment) group (p < 0.05). Notably, once-weekly MN therapy was at least as effective as the daily topical application of an EGCG + AA solution but markedly reduced the administration frequency and required dose. These results show that EGCG/AA-loaded γ-PGA MNs may be a convenient and promising therapeutic option for AD treatment.