| 研究生: |
鄭仲豪 Cheng, Chung-Hao |
|---|---|
| 論文名稱: |
具光裂解與溫度響應特性之高分子微胞:合成、性質鑑定與在藥物包覆的應用 Photocleavable and Thermoresponsive Polymeric Micelles: Synthesis, Characterization, and Application in Drug Encapsulation |
| 指導教授: |
吳文中
Wu, Wen-Chung |
| 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: | 2012 |
| 畢業學年度: | 100 |
| 語文別: | 中文 |
| 論文頁數: | 70 |
| 中文關鍵詞: | 雙親性嵌段共聚高分子 、熱感性高分子 、光敏性高分子 、藥物載體 |
| 外文關鍵詞: | amphiphilic block copolymers, photo-responsive polymer, thermo-responsive polymer, drug carriers |
| 相關次數: | 點閱:89 下載:2 |
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此論文針對一系列新穎雙親性嵌段共聚高分子poly(triethylene glycol methacrylate)-b-poly(o-nitrobenzyl methacrylate) (PTEGMA-b-PNBMA)進行研究,此雙親性嵌段共聚高分子同時具有熱感性及光敏性的性質,我們對其在水溶液中所自組裝形成的奈米結構和熱感性及光敏性的性質進行探討。我們以光敏性高分子PNBMA做為疏水性鏈段,當PNBMA照射特定波長的UV光後,會裂解並轉變為親水性鏈段;而PTEGMA為熱感性高分子,當溫度低於其最低臨界溶解溫度(lower critical solution temperature, LCST)時為親水性鏈段,當溫度高於LCST時轉變為疏水性鏈段。因此我們合成一系列的PTEGMA-b-PNBMA在溫度低於LCST時在水溶液中會自組裝形成微胞,以其作為藥物載體來包覆藥物 Doxorubicin (Dox),並利用高分子環境響應的特性造成微胞的崩解,以達到控制藥物釋放的目的。
我們所合成一系列新穎雙親性嵌段共聚高分子PTEGMA-b-PNBMA形成的微胞,藉由動態光散射粒徑分析儀(Dynamic Light Scattering, DLS)測量其粒徑為29.0~38.4 nm,並藉由包覆Nile red時不同的螢光強度推算出critical micelle concentration (CMC)為2.05×10-3~3.16×10-3 mM,以及利用不同溫度下穿透度來測得其在水溶液中LCST為40~42℃,並以UV-vis光譜儀的量測來了解不同照光時間下微胞溶液變化的情形。此外,我們更進一步利用PTEGMA-b-PNBMA高分子微胞來包覆藥物Dox,在較高的溫度下或有照光的情況下有利於高分子微胞的藥物釋放。
未來希望能藉由PTEGMA-b-PNBMA鏈段長度的調整,使PTEGMA-b-PNBMA高分子微胞的LCST接近於人體體溫,更進一步進行in vitro的實驗,包括細胞毒性的檢測,以及測試其在細胞內的藥物釋放作用情形。最終目標以PTEGMA-b-PNBMA高分子微胞作為藥物載體,在in vivo實驗中進行藥物傳輸及控制藥物釋放。
In this study, a series of new photo- and thermo-sensitive amphiphilic block copolymers, poly(triethylene glycol methacrylate)-b-poly(o-nitrobenzyl methacrylate) (PTEGMA-b-PNBMA) was synthesized and the polymeric micelles of these copolymers self-assembled in aqueous solution were investigated. PNBMA was a photo-cleavable polymer and it was the hydrophobic block of the copolymers. After the irradiation of UV light, PNBMA was broken and transformed from hydrophobic to hydrophilic. PTEGMA was a thermo-responsive polymer. PTEGMA was hydrophilic below the lower critical solution temperature (LCST). Above the LCST, PTEGMA transformed from hydrophilic to hydrophobic. Thus, the self-assembled micelles of these copolymers in aqueous solution could be utilized as nanocarriers in encapsulation of a hydrophobic drug, Doxorubicin (Dox), and the potential controlled release of Dox triggered by irradiation and/or temperature was explored.
We synthesized a series of new photo- and thermo-sensitive amphiphilic block copolymers which can self-assemble into micelles. The size of micelles was ranged from 29.04 to 38.41 nm by the dynamic light scattering. The critical micelle concentration of micelles could be evaluated by the photoluminescence spectra of encapsulating Nile red, and the results showed the CMCs are around 2.05×10-3~3.16×10-3 mM. The lower critical solution temperature of micelles were 40~42℃ by measuring transmittance. The transformation of the self-assembled nanostructures from polymeric micelles to unimers triggered after the irradiation of UV light was investigated by ultraviolet-visible spectroscopy. In addition, PTEGMA-b-PNBMA micelles were applied to load drug (Dox). At the higher temperature or the UV irradiation, PTEGMA-b-PNBMA micelles can achieve a more efficient drug release.
In the future, through the dedicate adjustment of chemical structures, the thermal transition temperature would be optimized around body temperature. This indicates that this new series of amphiphilic block copolymers, PTEGMA-b-PNBMA, possesses the potential to be applied as nanocarriers for in-vivo treatment with the capabilities of both active and passive target delivery.
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