| 研究生: |
紀凌濤 Chi, Ling-Tao |
|---|---|
| 論文名稱: |
利用三酸甘油酯之共包覆以提升高分子微胞之包覆藥物能力 Enhancement of Drug-Loading Capability for the Polymeric Micelles via Co-Encapsulation with Triglyceride |
| 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: | 2017 |
| 畢業學年度: | 105 |
| 語文別: | 中文 |
| 論文頁數: | 72 |
| 中文關鍵詞: | 雙親性嵌段共聚高分子 、溫感性高分子 、酸鹼感性高分子 、三酸甘油脂 、藥物包覆 |
| 外文關鍵詞: | amphiphilic copolymers, thermo-sensitive polymers, pH-sensitive polymers, triglyceride, drug loading |
| 相關次數: | 點閱:102 下載:3 |
| 分享至: |
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本研究將修飾的雙親性嵌段共聚高分子與三酸甘油脂在水溶液中共組裝形成微胞,並對此微胞進行奈米結構、環境應答、穩定性、藥物包覆及釋放進行探討。
雙親性嵌段共聚高分子為Poly[ε-caprolactone-b-(triethylene glycol methyl ether methacrylate-co-6-(methacrylamido)hexanoic acid)] [PCL-b-P(TEGMA-co-AHA)] (PTAHA),其中PCL為Poly(ε-caprolactone),做為疏水性的高分子鏈段,TEGMA為Triethylene glycol methyl ether methacrylate,做為高分子親水端的材料,AHA全名為 6-Aminohexanoic acid,具有羧酸根的功能性化合物,利用此特性控制藥物釋放的時機。調整AHA於高分子鏈段中的比例可以使微胞在酸性的環境中達到理想低臨界溶解溫度(Lower critical solution temperature, LCST),在中性時可以穩定存在。選用的三酸甘油脂為Tricaprin,其鏈段屬於三酸甘油脂的中間部分,又稱為中鏈甘油三脂(Medium chain triglyceride, MCT),將MCT與高分子混合形成微胞後,探討對於Doxorubicin (DOX)的包覆量是否能夠改善,同時微胞的性質亦是本研究關注的焦點。
本實驗將合成的高分子PTAHA自組裝形成微胞,在pH 5.33緩衝溶液下的LCST為32.2oC,添加MCT形成的微胞,LCST提升至35.8oC,這是因為添加MCT使微胞粒徑增加,增加了親水鏈段的距離。CMC的測試選用螢光性的Nile red做為探針,空白微胞的臨界微胞濃度(Critical micelle concentration,CMC)為0.049 mg/mL,添加0-40% MCT後的CMC相當於空白微胞的42.85~55.1%,CMC值降低是因為MCT增加了微胞的疏水性,提升微胞穩定性。熱分析實驗裡,從PTAHA/MCT微胞的測試結果看不出MCT對於PCL的影響,然而在模擬疏水環境的PCL及MCT混合物有明顯的差異,添加MCT能夠降低PCL的結晶度。在藥物包覆的實驗中,PTAHA/10%-20%MCT微胞能夠提升對Nile red的包藥量及效率,這是因為疏水體積擴大及PCL結晶度降低的關係,然而PTAHA/30-40%MCT微胞對Nile red的包覆能力下降,這是因為MCT與Nile red在共包覆時互為競爭關係,一旦MCT佔據疏水區域的空間增加,將會降低Nile red的包覆量;在Doxorubicin(DOX)的包覆實驗中,空白微胞包覆DOX的Loading content(LC)及Entrapment efficiency(EE)分別為5.27±0.33%、42.71±0.89%,隨著MCT的含量增加,微胞包覆DOX的能力越強,PTAHA/40% MCT微胞包覆DOX的LC及EE達到最高的8.11±0.3%、62.43±0.59%,除了添加MCT使微胞粒徑變大之外,PCL的低結晶度及MCT與DOX之間的氫鍵作用力都是能夠提高微胞包覆能力的重要因素。在穩定性的實驗中,PTAHA/40% MCT/DOX微胞的粒徑分布沒有明顯的變化,而PTAHA/DOX微胞的粒徑分布廣,顯示出藥物與高分子之間的作用力強弱是維持微胞穩定的重要因素。在藥物釋放的實驗中,PTAHA/MCT/DOX微胞及PTAHA/DOX微胞在酸性的環境下能夠有效地在1小時內將大量的藥物釋放出來,並且在中性的環境下沒有發生嚴重的突釋效應。從實驗結果說明PTAHA/MCT微胞適合作為包覆藥物的載體。
In this study, we developed a novel, dual-sensitive drug carrier based on polymeric micelles co-assembled from amphiphilic block copolymers, [PCL-b-P(TEGMA-co-AHA)] (PTAHA), with tricaprin, a kind of medium-chain triglyceride (MCT). PTEGMA possessed thermo-sensitive and AHA performed pH-sensitive in aqueous solution. The micelles, PTAHA/MCT, were designed to improve capability of Doxorubicin (DOX) loading and compared to blank micelles, PTAHA, as control. Among micelles, PCL and MCT formed a mixed hydrophobic domain known as micellar emulsion to encapsulate DOX. In physical properties, PTAHA/MCT micelles had bigger size and higher LCST at pH 5.33 buffer. In drug loading experiments, PTAHA/40% MCT had the highest loading content (LC) and entrapment efficiency (EE) to DOX. Moreover, PTAHA/MCT/DOX micelles performed superior stabilities at 37oC in aqueous solution. DOX in PTAHA/MCT micelles could release fast at acidic aqueous media within one hour while maintained in core at neutral. This was supposed that PTAHA/MCT micelles were adequate to be a drug carrier to encapsulate DOX.
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