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研究生:王冠雯
研究生(外文):Kuan-WenWang
論文名稱:可依需求控制藥物釋放之近紅外光敏感型高分子微針貼片
論文名稱(外文):Near-Infrared Sensitive Microneedles for On-demand Controlled Release
指導教授:陳美瑾陳美瑾引用關係
指導教授(外文):Mei-Chin Chen
學位類別:碩士
校院名稱:國立成功大學
系所名稱:化學工程學系碩博士班
學門:工程學門
學類:化學工程學類
論文種類:學術論文
論文出版年:2012
畢業學年度:100
語文別:中文
論文頁數:75
中文關鍵詞:高分子微針近紅外光控制釋放經皮傳輸
外文關鍵詞:Polymeric microneedlenear-infraredcontrolled releasetransdermal
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  微針貼片是一種結合針劑注射與傳統經皮貼片優點之無痛式微侵入型醫療裝置,其微米級針狀結構可在不刺激末梢神經的情況下刺穿皮膚角質層,有效地將藥物傳送至皮膚深層。然而目前發展之高分子微針系統多由材料之物性(如親疏水性與生物可降解性)決定藥物釋放的速度,尚無可依需求控制藥物釋放(on-demand control release)之劑型。本研究將生物相容性高分子聚己內酯(poly--caprolactone, PCL)與具光熱轉換效應之LaB6@SiO2奈米粒子(silica-coated lanthanum hexaboride nanoparticles, LaB6@SiO2 NPs)結合,開發出一可藉由近紅外光控制藥物釋放之新型高分子微針貼片。研究中利用25%(w/v)之聚己內酯溶液成功製備出金字塔型高分子微針,並由體外豬皮穿刺測試證實此微針貼片具有足夠之機械強度可刺穿皮膚達150200 m。於高分子微針中摻混0.31 wt%之奈米粒子,製備近紅外光靈敏型微針貼片,經近紅外光照射測試,證實此微針確實能在吸收近紅外光後加熱微針使其熔化,約在照光90秒後全熔。將微針刺入豬皮進行體外近紅外光驅動藥物釋放實驗,由“連續式照射”模式證明,包藥之微針確實可在照光熔化後釋放出所包覆之藥物,且藥物釋放之劑量隨照光時間增加而上升;設定微針受近紅外光照射達50度後維持恆溫3分鐘為一照光週期進行“間歇式照射”測試,結果顯示微針僅在照光時(LASER ON)才釋放藥物,且藥物釋放之劑量可隨照光次數(週期)增加而呈比例上升,顯示微針之藥物釋放確實可依照光與否及照光頻率所控制。將微針刺入大鼠背部皮膚並以間歇式照射進行體內藥物釋放實驗,由3D全光譜活體分子影像系統及共軛焦顯微影像系統分析結果均證實,此光敏性微針確實可於活體中達到以近紅外光驅動並控制其藥物釋放之效果,未來將可應用於耐熱型藥物(如DNA疫苗與抗癌藥)之經皮傳輸上,深具臨床應用潛力。
Microneedle (MN) patches, combining the advantages of hypodermic needles and transdermal patches, have been proposed as a new tool for transdermal drug delivery, because of their efficient delivery and lack of pain. Drug release from current available polymeric microneedles mostly depends on the physical properties of polymer; however, little work involves microneedles which can provide “on demand” drug delivery. In this study, a polymeric microneedle patch, which is consisted of biodegradable polymer and photothermal nanoparticles, silica-coated lanthanum hexaboride nanoparticles (LaB6@SiO2 NPs), using near-infrared (NIR) light as a trigger for drug release was reported as a novel transdermal drug delivery device. The skin insertion tests showed that the developed polymeric microneedles were strong enough to insert into the epidermis layer (~150 m) of porcine cadaver skin. After encapsulating LaB6@SiO2 NPs within MNs, the resulting microneedles were shown to have NIR-sensitive property and melt by stimulation with NIR light due to the local heating of the NPs. In vitro triggered release study showed that the drug release from the microneedles can be easily and non-invasively controlled by the adjustment of the irradiation time and frequency of NIR light. The continuous irradiation test demonstrated the encapsulated drugs can be released from the melted microneedles, and the amount of released drug was increased with increasing the irradiation time. The intermittent irradiation test demonstrated the melting of NIR-sensitive MNs exhibit reversible and repeatable heating when exposed to NIR light, and the drug release occurred in a stepwise fashion, where LASER ON induced a steep increase in drug release, and LASER OFF permitted only very little drug from being released over a long period. The animal study demonstrated the feasibility of the NIR-sensitive MNs for in vivo applications. It is expected that the NIR-sensitive microneedles may provide a simple and convenient technology for transdermal delivery of heat-stable drugs (such as DNA vaccine, or anti-cancer drugs etc.) and facilitate the development of drug delivery system.
目錄
摘要 I
Abstract II
致謝 III
目錄 IV
圖目錄 VII
表目錄 X
第一章 緒論 1
1.1 經皮藥物傳輸與皮膚構造 1
1.1.1 經皮藥物傳輸 1
1.1.2 皮膚構造 1
1.1.3 藥物經皮吸收的途徑及其作用機制 3
1.2 經皮給藥系統 5
1.2.1 經皮給藥之特性 5
1.2.2 經皮給藥系統之發展 6
1.3 微針貼片系統 8
1.3.1 微針之發展 8
1.3.2 藥物包覆及其應用方式 9
1.3.3 高分子微針系統發展現況 11
1.4 藥物控制釋放 13
1.4.1 藥物控制釋放之重要性 13
1.4.2 遠端遙控藥物釋放(remotely controlled drug delivery) 14
1.4.3 近紅外光(near infrared, NIR)驅動釋放 15
1.4.4 奈米粒子與光熱轉換效應 17
1.4.5披覆二氧化矽之六硼化鑭奈米粒子之材料特性分析 18
1.5 聚己內酯(polycaprolactone, PCL) 21
1.6 研究目的 22
第二章 實驗方法 24
2.1 實驗藥品與儀器設備 24
2.1.1 實驗藥品、耗材與動物 24
2.1.2 儀器設備 26
2.2 近紅外光靈敏型微針貼片 28
2.2.1 聚己內酯微針貼片之製備 28
2.2.2 微針機械強度測試 30
2.2.3 體外豬皮穿刺測試 30
2.2.4 光敏型微針之製備及其光驅動熔化效應測試 31
2.2.5 LaB6@SiO2奈米粒子細胞毒性測試(cell viability) 32
2.3 近紅外光控制釋放之光敏型微針貼片 35
2.3.1 藥物包覆與定量 35
2.3.2 不同照光模式下微針升溫熔化之熱像分析 37
2.3.3 近紅外光遙控藥物釋放-體外實驗 38
2.3.4 近紅外光遙控藥物釋放-體內實驗 39
第三章 結果與討論 41
3.1 近紅外光靈敏型微針貼片 41
3.1.1聚己內酯高分子微針貼片 41
3.1.2 微針機械強度分析 42
3.1.3 豬皮體外穿刺結果 43
3.1.4 光敏型微針之製備及其光驅動熔化效應測試 45
3.1.5 LaB6@SiO2奈米粒子細胞毒性評估 46
3.2藥物釋放型光敏性微針貼片 48
3.2.1 包覆藥物之光敏型微針及其定量分析 48
3.2.2不同照光模式下微針升溫熔化之熱像分析 50
3.2.3 近紅外光遙控藥物釋放-體外實驗 55
3.2.4 近紅外光遙控藥物釋放-體內實驗 60
3.2.5 討論 66
第四章 結論 67
參考文獻 68

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