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研究生： 丁一釗
Ding, I-Chao
論文名稱： 可調控待克芬那釋放之光應答型微針應用於病人自控式疼痛治療
On-off switchable release of diclofenac from light-responsive microneedles for patient-controlled pain therapy
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： 2016
畢業學年度： 104
語文別： 中文
論文頁數： 58
中文關鍵詞： 光應答型微針 、近紅外光 、控制釋放
外文關鍵詞： Light-responsive microneedle, Near-infrared light, On-demand controlled release
相關次數： 點閱：99  下載：3 
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    • 本研究利用離心製程製備出水溶性高分子針尖結合鐘狀微載體聚己內酯(polycaprolactone, PCL)之新一代光應答型微針。將微載體包覆止痛藥物待克芬那(diclofenac)及光敏劑靛青綠(indocyanine green, ICG)，光敏劑可在吸收近紅外光後將其轉換為熱能，加熱聚己內酯使其熔化進而釋放裝載藥物。由於純PCL微針有其較弱之機械強度，新一代微針構型藉由針尖高強度之水溶性高分子提升整體強度，於穿刺時將鐘狀微載體聚己內酯一併刺入，使PCL完整鑲嵌於皮膚中達到有效之藥物釋放。由材料測試機測試結果顯示，微針之機械強度比純聚己內酯微針有明顯上升，當微針形變量300 µm時，承受力量約為純聚己內酯微針之4倍。經由體外皮膚穿刺結果證實，穿刺深度可達700-750 m。在近紅外光照光實驗中，穿刺後之微針在接受不同照光模式，微針長度隨著照光時間增長而逐漸熔化變短。體外藥物釋放實驗證實，微針僅在照射近紅外光時才釋放藥物，於連續式照光實驗中，控制照光溫度為48 C，強度5.0 W/cm2之808-nm雷射，發現藥物釋放量隨照光時間增加而有等比例上升的趨勢。設定微針受近紅外光照射達48 C後維持恆溫3分鐘為一照光週期進行'間歇式照射'測試，結果顯示藥物釋放之劑量可隨週期增加呈階梯式上升(每個週期釋放21 ± 1 % (n = 5)之Diclofenac；23 ± 2 % (n = 5)之ICG)，且能重複驅動釋放4次。由動物實驗發現，此光應答型微針可成功的刺入鼠皮，穿刺深度達800-1200 m並將鐘狀PCL微載體鑲嵌於活體中，證實確實可成功刺穿角質層並鑲嵌於皮膚中。此外，此微針依照光與否有其釋放藥物之開關效應及準確經皮傳輸藥物之能力。

    In this study, we developed a patch-dissolvable microneedles which combine PVP/PVA tips with bell-shaped PCL structures by a new two-step molding process.We used biodegradable polycaprolactone (PCL), encapsulated analgesic agent – diclofenac and indocyanine green (ICG), to fabricate near-infrared (NIR) light-responsive polymer microneedle (MN). After absorbed NIR, ICG loaded in MN could convert the energy into heat to melt PCL and release drugs We focused on the feasibility of MN delivering analgesic agents transdermally and its mechanical strength. MN made by polycarprolatone have low mechanical strength. The material testing machine tests showed that we could improve the mechanical strength of MN by new fabrication. At the displacement of 0.3 mm, the force of PVP/PVA-PCL MNs is four times higher than PCL’s. The skin insertion tests proved that the microneedles could be fully inserted into the skin with penetration depth of 700-750 m in vitro test and 800–1200 µm in vivo test. The MNs with ICG can be melted and become smaller by NIR irradiation. In vitro drug test demonstrated that the amount of released drugs can be controlled accurately by adjusting the irradiation periods and exposure time.The continuous irradiation test demonstrated the amount of released drug increased with irradiation time. The amount of released drugs can be controlled by adjusting the irradiation periods, and the release of drugs exhibited in a stepwise function (21 ± 1 % of diclofenac, 23 ± 2 % of ICG) by intermittent irradiation.

    摘要.................................................I Abstract..........................................VIII 致謝................................................IX 表目錄.............................................XII 圖目錄............................................XIII 第一章 緒論..........................................1 1.1 藥物控制釋放.....................................1 1.1.1 控制釋放系統...................................1 1.1.2 驅動控制釋放系統...............................3 1.1.3 近紅外光(near-infrared light, NIR)驅動釋放.....4 1.2 光熱轉換效應(Photothermal effect)................5 1.2.1 光熱轉換效應...................................5 1.2.2 靛青綠(indocyanine green, ICG).................5 1.3 疼痛治療.........................................7 1.3.1 疼痛簡介.......................................7 1.3.2 癌症止痛.......................................8 1.3.3 止痛藥分類.....................................9 1.3.4 Diclofenac（雙氯芬酸；Valtaren, 待克芬那）....11 1.4 高分子微針系統..................................12 1.5生物可降解性高分子...............................13 1.5.1 生物可降解性高分子之分類......................13 1.5.2 聚己內酯(polycaprolactone, PCL)...............13 1.6 研究目的........................................16 第二章 材料與方法...................................19 2.1 實驗藥品與儀器設備..............................19 2.1.1 實驗藥品、耗材與動物..........................19 2.1.2 儀器設備......................................20 2.2 光應答型微針之製備..............................22 2.2.1 微針之製備....................................22 2.2.2 微針機械強度測試..............................25 2.2.3 體外豬皮穿刺測試..............................26 2.3 近紅外光驅動藥物釋放............................27 2.3.1 光應答型微針藥物包覆與定量....................27 2.3.2 光驅動熔化效應測試及熱影像分析................29 2.3.3 體外藥物釋放定量實驗..........................30 2.4 體內近紅外光驅動釋放及熱傷害評估................31 2.4.1 活體大鼠穿刺測試..............................31 第三章 結果與討論...................................33 3.1 光應答型微針之製備..............................33 3.1.1 微針之製備....................................33 3.1.2 微針機械強度測試..............................34 3.1.3 體外豬皮穿刺測試..............................36 3.2 近紅外光驅動藥物釋放............................37 3.2.1 光應答型微針藥物包覆與定量....................37 3.2.2 光驅動熔化效應測試及熱影像分析................40 3.2.3 體外藥物釋放定量實驗..........................47 3.3 活體大鼠穿刺測試................................50 第四章 結論.........................................51 參考文獻............................................52

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