異位性皮膚炎(atopic dermatitis, AD)是一種反覆發作的皮膚過敏性疾病，主要由第二型輔助T細胞過度免疫造成。典型症狀包括皮膚發癢、腫脹、紅疹與血中E型免疫球蛋白升高(IgE)。臨床上治療的方式除口服用藥，較常見的是塗抹他克莫司(tacrolimus, TAC)藥膏於患部，其可抑制T細胞生長與分化，緩解發炎反應。患者需每天塗抹皮膚兩次，且塗抹後會有灼熱感等症狀，常導致病患擅自停藥。本研究以生物可降解之聚乳酸甘醇酸[poly(lactic-co-glycolic acid)，PLGA]包覆他克莫司以緩釋藥物，並結合具免疫調節、保濕及傷口修復作用之聚麩胺酸鹽(poly-γ-glutamic acid, γ-PGA)，製成雙層式PLGA/γ-PGA微針，探討其對改善異位性皮膚炎老鼠病症之功效。當微針刺入皮膚三分鐘後，γ-PGA層可快速被皮膚組織液溶解，進入真皮層中進行免疫調節，並發揮保濕與傷口修復的功效；TAC-loaded PLGA (LA:GA = 50:50) 針尖則可鑲嵌於皮膚內約629 ± 56 μm (n = 5)，包藥量為123.2 ± 9.3 μg (n = 5)，可於體外緩慢釋放TAC長達四週，達到長效治療皮膚炎之目的。PLGA/γ-PGA微針穿刺皮膚後傷口可於兩天內修復，而PLGA/PVP-PVA微針產生之傷口則於第5天才癒合，推測γ-PGA有幫助傷口修復的作用。將微針施打於異位性皮膚炎Nc/Nga小鼠上，治療35天後發現，微針組(PLGA 50:50)之皮膚炎分數由5分降至2分，相較於每週塗抹5次TAC藥膏組(約3分)，更能改善發炎指數，並明顯減緩皮膚炎所導致之表皮增厚(由174.9 ± 23.1降至32.8 ± 4.9 μm)與肥大細胞浸潤(數量由68.5 ± 20.2/0.35 mm2降至29.2 ± 5.8/0.35 mm2)等現象。檢測小鼠體內過敏反應相關之抗體，發現微針治療能有效抑制IgE及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之產生。以上結果證實，具保濕、促進傷口修復與可緩釋TAC藥物之雙層式PLGA/γ-PGA微針，每個月僅須施打一次，可大幅降低每日塗抹藥膏的不便性，有潛力取代臨床上的劑型，成為一方便且有效的AD療法。

Atopic dermatitis (AD) is a chronic inflammatory skin disease that is induced by T helper type 2–polarized immune responses and has the characteristics of itch, swelling, eczema, and elevated serum IgE levels. This study presents a double-layered [poly(lactic-co-glycolic acid), PLGA]/poly-γ-glutamic acid (γ-PGA) microneedle (MN) and investigate its efficacy for alleviating AD symptoms. An immunosuppressant drug, tacrolimus (TAC), was encapsulated in the PLGA tip and then combined with an immunomodulatory active compound, γ-PGA layer with wound healing and moisturizing effect. When inserted into the skin, the γ-PGA layer can be quickly dissolved by skin interstitial fluid within 3 min and into the dermis to activate the dendritic cells; the TAC-loaded PLGA tip can be embedded in the skin at a depth of for sustained release of TAC to reduce skin inflammation. The TAC loading amount in the PLGA tip was, which provided an extended release for up to 4 weeks. The MN-created microchannels quickly resealed within two days; however, the skin punctured by the MNs without γ-PGA required five days to recover its barrier function. After applying the MNs to the Nc/Nga mice with AD-like symptoms, the serum levels of IgE, IgG1, and IgG2a were also reduced in the MN group, indicating that the MNs suppress not only the Th2-type (IgG1 and IgE) but also the Th1-driven antibodies (IgG2a). Additionally, the MN treatment can significantly inhibit inflammation-induced epidermal thickening and mast cell infiltrations. These results show that the double-layered MN not only has the wound healing activity, but also provides sustained release of TAC for long-term management of skin inflammatory. Compared to daily topical administration, once-a-month MN treatment greatly reduces dosing frequency and has the potential as an attractive alternative in the treatment of AD.

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