雄性禿為一種漸進式的多因性掉髮疾病，其發病受到年齡、性別、遺傳、激素與氧化壓力等因素所影響，由於超過50 %的年長男性與15 %更年期後女性罹患雄性禿，因此尋求有效的抗掉髮策略具有高度需求性，為了改良目前雄性禿外用塗抹米諾地爾與口服非那雄胺劑型須每日使用治療之不便，同時提高藥物傳遞效率並提升治療效益，本研究開發包覆米諾地爾(Minoxidil, MXD)/薑黃素(Curcumin, CUR)之聚乳酸甘醇酸[poly(lactic-co-glycolic acid)，PLGA]植入式微針，希望透過微針劑型以降低給藥頻率與提升藥物傳遞效率，同時米諾地爾可刺激血管增生擴張，以改善雄性禿毛囊之血氧供給，而薑黃素可抑制自由基積累，藉此消除雄性禿發生區域之氧化壓力，最終聯合藥效與劑型之優勢以達到持續性改善、治療雄性禿之目的。為了瞭解微針應用於雄性禿治療之潛力，本研究針對包覆米諾地爾/薑黃素之PLGA微針(MXD/CUR MN)進行定性、定量分析，實驗結果顯示微針穿刺深度可達474 ± 146 μm (n = 8)，穿刺傷口可於三天內完全癒合。每片微針含有51 ± 4 μg (n = 6)米諾地爾與32 ± 2 μg (n = 6)薑黃素;於模擬生理環境之條件下，微針內米諾地爾與薑黃素分別可達到9天與14天之持續釋放，並且微針置放一個月後仍保有原始抗氧化活性。藉由施打兩片MXD/CUR MN於雄性禿小鼠背部皮膚，經過四週治療後可有效改善雄性禿症狀、促進毛髮生長，其再生毛髮覆蓋率可達95.9 ± 4.8 % (n = 4)，且高於外用塗抹米諾地爾之83.0 ± 8.8 % (n = 4)，與健康組小鼠相比無明顯統計學差異;除了毛髮外觀、直徑與健康組相當之外，皮膚厚度與生長期毛囊密度與雄性禿誘導組相比具有明顯提升，並可觀察到新生毛囊細胞、血管分佈於毛囊微環境之現象;同時有效降低組織內氧化壓力積累，根據以上結果可證明MXD/CUR MN可持續且有效改善雄性禿症狀，有潛力成為未來雄性禿治療之新選擇。

In this study, a [poly (lactic-co-glycolic acid, PLGA)] implantable microneedles loaded with minoxidil (MXD)/curcumin (CUR), abbreviated MXD/CUR MN, was developed. After being applied to the mouse skin for 6 minutes, the microneedle backing layer quickly dissolves. allowing the PLGA tips to embed at the border between the dermis and subcutis. These tips then release the drugs for up to two weeks. The microchannels formed by the microneedle puncture fully recover within 72 hours. The MXD/CUR MN still retains its original antioxidant activity after one month of storage. Two microneedle patches were administered to C57BL/6 male mice with androgenetic alopecia. alopecia. Significant hair regeneration was observed after 4 weeks of treatment, and the regenerated hair coverage rate was higher than that of topical minoxidil. No significant statistical differences were found when compared to healthy mice. Analysis of hair diameter, skin thickness, and hair follicle density during the anagen phase indicated that the MXD/CUR microneedles effectively improved the symptoms of androgenetic alopecia. There was also evidence of hair follicle cell proliferation and increased blood vessel distribution in the hair follicle microenvironment. Based on these results, MXD/CUR microneedles can sustainably and effectively improve the symptoms of androgenetic alopecia and has the potential to become a new option for the treatment of androgenetic alopecia in the future.

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