| First Author | Chen MC | Year | 2020 |
| Journal | Acta Biomater | Volume | 114 |
| Pages | 183-192 | PubMed ID | 32688089 |
| Mgi Jnum | J:303145 | Mgi Id | MGI:6511407 |
| Doi | 10.1016/j.actbio.2020.07.029 | Citation | Chen MC, et al. (2020) Poly-gamma-Glutamate microneedles as transdermal immunomodulators for ameliorating atopic dermatitis-like skin lesions in Nc/Nga mice. Acta Biomater 114:183-192 |
| abstractText | 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, low-molecular-weight (200-400 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. |
