異位性皮膚炎(atopic dermatitis)是一種反覆發作的過敏性皮膚疾病，與免疫失調有關，並經常伴隨皮膚乾癢、脫皮、紅腫等症狀。本研究結合聚麩胺酸鹽(poly-γ-glutamate, γ-PGA)微針及聚己內酯(polycaprolactone, PCL)支撐軸陣列，開發兩種分子量(200-400 kDa、1100 kDa)之聚麩胺酸鹽快溶型微針貼片，應用於改善自發性異位性皮膚炎動物模型(Nc/Nga小鼠)之皮膚病症，與評估其免疫調節的潛力。兩款微針皆可於施打於皮膚約兩分鐘內完全溶解，並可快速移除聚己內酯支撐軸貼片，將聚麩胺酸鹽釋放於皮膚約400-500 µm之深度，相當於表皮層與真皮層中，為富含抗原呈現細胞的位置。每片可傳入約750 µg聚麩胺酸鹽；微針施打對皮膚所造成的微傷口，可於3-4小時內完全癒合，可降低感染風險；由活體螢光分佈結果可知，200-400 kDa以及1100 kDa分子量聚麩胺酸鹽於施打後第0天至第1天內，大部分會迅速於皮膚中擴散與被吸收，並可分別存在於皮膚至少2天與6天；將聚麩胺酸鹽微針施打於Nc/Nga小鼠，並檢測體內與過敏反應相關之IgE抗體，發現分子量1100 kDa之聚麩胺酸鹽可有效抑制IgE濃度的上升，且兩種分子量之聚麩胺酸鹽微針均能有效地抑制代表體液型免疫反應(Th2)與細胞型免疫反應(Th1)之抗體：IgG1及IgG2a，亦均能改善皮膚炎病症，包含皮膚角化過度、棘狀層肥厚、組織腫脹以及肥大細胞浸潤之情形。以上結果證實，本研究所開發之聚麩胺酸鹽微針，可快速且穩定地經皮釋放，並調節免疫反應，改善皮膚炎之病症，有潛力應用於異位性皮膚炎患者之治療，提升病人的生活品質。

Atopic dermatitis (AD) is a complex inflammatory skin disease that is closely related to dysregulation of the immune system and with the characteristic of itch and eczema. This study presents a dissolving microneedle system, which comprises poly-γ-glutamate (γ-PGA) microneedles (MNs) with a polycaprolactone supporting array, for investigating the effect of γ-PGA MNs and their molecular weights (MW) including low MW (200-400 kDa) and high MW (1100 kDa), on spontaneous AD-like skin disease in Nc/Nga mice. After applying MNs for two minutes, MNs can be quickly dissolved within the mouse skin with the amounts of 750 µg γ-PGA per patch. A histological examination shows that MNs are strong enough to pierce into mouse skin at a depth of approximately 400-500 µm, where corresponds to insertion through the epidermis and into the dermis, which is rich in the antigen-presenting cells. The microchannels created by the MN insertion can completely heal within 3-4 h, thus reducing the risk of infection. After insertion, we found that a notable decrease in the fluorescent signals of both MWs of MNs on Day 1, and their signals of low and high MW γ-PGA could be detectable up to 2 and 6 days, respectively. After applying the MNs to the Nc/Nga mice, the serum levels of IgE, IgG1, and IgG2a were negatively regulated, indicating that γ-PGA MNs suppress not only the Th2-type (IgG1 and IgE) but also the Th1-driven antibodies (IgG2a). Moreover, the AD symptoms, such as hyperkeratosis, acanthosis, tissue swelling and massive infiltrations of mast cells into the skin lesions, of the MN-treated group was also alleviated compared to the non-treated group. This study demonstrates that the developed γ-PGA MNs have potential to serve as a new therapeutic tool for AD treatment.

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