| 研究生: |
劉至翰 Liu, Chih-Han |
|---|---|
| 論文名稱: |
局部緩釋雙效藥物之雙邊型微針系統應用於雄性禿之治療 Local Sustained Release of Dual-Acting Therapeutics from Bilateral Microneedle Systems for Androgenetic Alopecia Treatment |
| 指導教授: |
陳美瑾
Chen, Mei-Chin |
| 學位類別: |
碩士 Master |
| 系所名稱: |
工學院 - 化學工程學系 Department of Chemical Engineering |
| 論文出版年: | 2024 |
| 畢業學年度: | 112 |
| 語文別: | 中文 |
| 論文頁數: | 136 |
| 中文關鍵詞: | 雄性禿 、微針貼片 、非那雄胺 、薑黃素 、表沒食子兒茶素沒食子酸酯 |
| 外文關鍵詞: | Androgenetic alopecia, Microneedles, Finasteride, Curcumin, Epigallocatechin gallate |
| 相關次數: | 點閱:29 下載:0 |
| 分享至: |
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全球有70%男性與40%女性一生中會受到雄性禿影響而掉髮,嚴重影響患者的生活品質,主要成因為賀爾蒙失調與活性氧分子(ROS)過量所致。本研究選用可減少雄性激素-受體複合物形成之藥物非那雄胺與可調節平衡ROS的天然抗氧化劑作為活性成分以改善落髮。為了降低給藥頻率與避免全身性副作用,以微針作為給藥系統。本研究設計雙邊緩釋型及緩釋加快溶型共兩款微針,前者為兩邊針尖皆使用聚乳酸-羥基乙酸共聚物(PLGA)分別包覆非那雄胺或薑黃素,後者為一邊針尖使用PLGA包覆非那雄胺另一邊針尖使用玻尿酸(HA)包覆表沒食子兒茶素沒食子酸脂(EGCG)。微針總長為795 ± 3 µm (n = 6),PLGA針尖長385 ± 10 µm (n = 6),分別包覆非那雄胺37.3 ± 3.6 µg/片 (n = 6)、薑黃素26.2 ± 3.7 µg/片 (n = 6);HA針尖長567 ± 18 µm (n = 6),包覆EGCG 20.3 ± 1.8 µg/片 (n = 6)。微針穿刺後PLGA針尖可鑲嵌於皮內達到96至98 %之藥物傳遞效率,而HA針尖則於皮內迅速溶解,傳遞效率落在85到90%之間,穿刺後之微傷口均可於72小時內癒合。非那雄胺與薑黃素可分別由PLGA針尖長效釋放達77與63天,且分別在第21天到63天與第10天到49天呈現長時間等速釋放,每日釋放量分別約為0.44 µg非那雄胺與0.22 µg薑黃素,水溶性EGCG則能在HA溶解後在皮膚中滯留10天。薑黃素與EGCG包覆於微針中保存一個月之抗氧化能力仍分別有同藥量溶液之95.7 ± 4.8 % (n = 6)與95.7 ± 2.4 % (n = 6),說明製程不影響抗氧化劑的活性,且能穩定存放一個月。目前已成功以塗抹睪固酮誘導小鼠雄性禿模型,在28天後小鼠背部毛髮仍未長出,休止期毛囊比例也明顯提高,同時組織內ROS含量為健康組的2倍以上。未來將進一步以動物實驗評估是否能透過非那雄胺與抗氧化劑協同治療,加上微針施打引起傷口修復來刺激血管新生促進生髮,成為雄性禿治療的新方法。
Androgenetic alopecia (AGA) is the most common hair loss disorder with progressive hair follicle miniaturization affecting both men and women. hormonal imbalance and excessive reactive oxygen species (ROS) are the main causes of AGA. This study designed two types of Bilateral microneedles (MNs) : bilateral sustained-release MNs, both needle tips are coated with poly(lactic-co-glycolic acid) (PLGA) encapsulating finasteride or curcumin ; sustained plus rapid-release MNs, one side needle tips use PLGA to encapsulate finasteride and the other side use hyaluronic acid (HA) to encapsulate epigallocatechin gallate (EGCG). After MNs puncture the skin, the PLGA needle tips embed in the dermis, achieving a delivery efficiency of 96 to 98%, whereas the HA needle tips rapidly dissolve with a delivery efficiency ranging from 85 to 90%. The wounds heal within 72 hours. Experiments show that finasteride and curcumin can be released from the PLGA needle tips for 77 and 49 days, respectively, while EGCG remains in the skin for 10 days after HA dissolution. The antioxidant capabilities of curcumin and EGCG in the microneedles remain at 95%, indicating that the fabrication process does not affect the efficacy of the antioxidants and allows stable storage for up to one month. Currently, AGA has been successfully induced in mice through topical application of testosterone. After 28 days, hair on the back of the mice did not regrow, the thickness of the dermis decreased, and the proportion of telogen phase hair follicles increased, and the ROS content in the tissue is more than twice that of the healthy group. Future studies will continue the efficacy test, combined treatment of finasteride and antioxidants, along with the wound healing induced by microneedle application, to stimulate angiogenesis and promote hair growth, potentially becoming a new method for treating AGA.
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校內:2029-08-06公開