Poly-γ-Glutamate microneedles as transdermal immunomodulators for ameliorating atopic dermatitis-like skin lesions in Nc/Nga mice

Atopic dermatitis (AD), a common, relapsing, inflammatory disorder of the skin, is associated with T helper type 2 (Th2)-biased immune responses. Despite the efficacy of existing drugs for AD treatment, their safety and side effects cause concern. The present study describes the use of dissolvable poly-gamma glutamate (gamma-PGA) microneedles (MNs) with immunomodulatory effects for effectively relieving AD-like symptoms in Nc/Nga mice. gamma-PGA MNs can easily penetrate the epidermis and release gamma-PGA into the dendritic cell-rich dermis to interact with dendritic cells for modulating immune responses. Transdermal administration of high-molecular-weight (HMW, 1100 kDa) gamma-PGA MNs significantly reduced clinical dermatitis scores, epidermal thickness, and mast cell infiltration in mice by downregulating immunoglobulin (Ig)E and IgG1 levels (Th2-associated antibodies) compared with the AD control group. However, lowmolecular-weight (20 0-40 0 kDa) gamma-PGA MNs ameliorated AD-like skin lesions less effectively than HMW gamma-PGA MNs, thus indicating that the MW of gamma-PGA may affect its immunomodulatory properties. Notably, the mouse skin quickly recovered its barrier function within 4 h after MN application. No weight loss or abnormality was observed in the MN-treated mice during the 8-week treatment period. These results suggest that the gamma-PGA MNs represent an innovative, safe, and reliable therapeutic strategy for AD management. Statement of Significance This study is the first to explore the feasibility of using poly-gamma-glutamate (gamma-PGA) microneedles (MNs) as transdermal immunomodulators for improving atopic dermatitis (AD) symptoms and to evaluate their immunomodulatory effect in mice with spontaneously developed AD. Transdermal administration of gamma-PGA MNs enables the gamma-PGA to localize in the skin for activation of dermal dendritic cells, thus modulating immune responses. We demonstrate that high-molecular-weight gamma-PGA MNs can be retained in the skin for at least 6 days and effectively suppress AD-like skin lesions in mice by reducing infiltration of mast cells and downregulating Th2-associated antibody production (IgE and IgG1). The developed MN device has the potential to replace conventional therapy and to become an innovative treatment strategy for AD. (C) 2020 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.