論文 - 詳細
| RRC ID | 60832 |
|---|---|
| 著者 | Chen MC, Chen CS, Wu YW, Yang YY. |
| タイトル | Poly-γ-Glutamate microneedles as transdermal immunomodulators for ameliorating atopic dermatitis-like skin lesions in Nc/Nga mice. |
| ジャーナル | Acta Biomater |
| Abstract |
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. STATEMENT OF SIGNIFICANCE: 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. |
| 巻・号 | 114 |
| ページ | 183-192 |
| 公開日 | 2020-9-15 |
| DOI | 10.1016/j.actbio.2020.07.029 |
| PII | S1742-7061(20)30415-3 |
| PMID | 32688089 |
| MeSH | Administration, Cutaneous Animals Cytokines Dermatitis, Atopic* / drug therapy Immunologic Factors / therapeutic use Mice Polyglutamic Acid / analogs & derivatives Skin |
| IF | 6.638 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 1 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| 実験動物マウス | RBRC01059 |