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

• Published in: Acta biomaterialia Vol. 114; pp. 183 - 192
• Main Authors: Chen, Mei-Chin, Chen, Chia-Sui, Wu, Yan-Wei, Yang, Yin-Yin
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 15.09.2020; Elsevier BV
• Subjects: Administration, Cutaneous; Allergy; Animals; Antibodies; Atopic dermatitis; Cytokines; Dendritic cells; Dermatitis; Dermatitis, Atopic - drug therapy; Dermis; Epidermis; Immunoglobulin G; Immunoglobulins; Immunologic Factors - therapeutic use; Immunomodulation; Immunomodulators; Immunomodulatory; Immunosuppressive agents; Inflammatory; Inflammatory diseases; Lesions; Lymphocytes T; Mice; Needles; Poly-γ-glutamate; Polyglutamic Acid - analogs & derivatives; Side effects; Skin; Skin diseases; Skin lesions; Transdermal delivery; Weight loss; Inflammatory; Transdermal delivery; Allergy; Immunomodulatory; Poly-γ-glutamate
• ISSN: 1742-7061; 1878-7568
• DOI: 10.1016/j.actbio.2020.07.029

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-γ-glutamate (γ-PGA) microneedles (MNs) with immunomodulatory effects for effectively relieving AD-like symptoms in Nc/Nga mice. γ-PGA MNs can easily penetrate the epidermis and release γ-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) γ-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, low-molecular-weight (200–400 kDa) γ-PGA MNs ameliorated AD-like skin lesions less effectively than HMW γ-PGA MNs, thus indicating that the MW of γ-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 γ-PGA MNs represent an innovative, safe, and reliable therapeutic strategy for AD management. This study is the first to explore the feasibility of using poly-γ-glutamate (γ-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 γ-PGA MNs enables the γ-PGA to localize in the skin for activation of dermal dendritic cells, thus modulating immune responses. We demonstrate that high-molecular-weight γ-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. [Display omitted]