| 研究生: |
陳雲耑 Chen, Yun-Duan |
|---|---|
| 論文名稱: |
製備嵌段共聚胺酸與雙醣修飾聚胺酸及礦化之自組裝高分子載體應用於藥物傳輸 Preparation of block copolypeptides and glycopeptides and mineralization of self-assembled glycopeptides carriers for drug delivery |
| 指導教授: |
詹正雄
Jan, Jeng-Shiung |
| 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: | 105 |
| 中文關鍵詞: | 聚胺基酸 、分子自組裝 、醣類 、藥物傳輸 、點擊化學 |
| 外文關鍵詞: | Polypeptides, self-assembly, saccharides, drug delivery, click chemistry |
| 相關次數: | 點閱:134 下載:1 |
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於本研究中,經由胺基酸N-carboxyanhydrides (NCAs)的開環聚合反應(Ring-opening polymerization)我們製備得到嵌段共聚胺基酸, poly(γ-benzyl-L -glutamate)-block-poly(L-phenylalanine) (PBLG-b-PPhe)與poly(γ-benzyl-L -glutamate)-block-polyglycine (PBLG-b-PGly)。在移除PBLG嵌段上的benzyl保護基後,我們得到水溶性的雙親性嵌段共聚胺基酸, poly(L-glutamic acid)-block-poly(L-phenylalanine) (PLGA-b-PPhe)與poly(L-glutamic acid)-block -polyglycine (PLGA-b-PGly),接著經由點擊化學的銅催化炔-疊氮環化加成反應(Click chemistry:Copper-catalyzed Azide-Alkyne Cycloaddition),我們成功地製備得到具有雙醣修飾的雙親性胺基酸嵌段共聚物自組裝結構,Lactobionic acid-block-poly(L-glutamic acid)-block-poly(L-phenylalanine) (Lac-b-PLGA-b-PPhe)與Lactobionic acid-block-poly(L-glutamicacid)-block -polyglycine (Lac-b-PLGA-b-PGly)。本雙親性胺基酸嵌段共聚物於水溶液中會自組裝形成微胞(Micelles)結構,在經由乳醣酸的修飾並且經由Calcium Phosphate (CaP)的礦化沉積後,此具有半乳醣基之雙親性胺基酸嵌段共聚物形成的微胞可以成為具有標定肝癌細胞功能的藥物載體。
在嵌段共聚胺基酸,PBLG-b-PPhe與PBLG-PGly,的組成以及結構性質分析上,我們使用了凝膠滲透層析儀(GPC)、紅外線光譜儀(FT-IR)、熱分析儀(DSC)、廣角度X光散射(WAXS)以及核磁共振光譜儀(13C NMR 與1H NMR)等儀器鑑定。接下來,藉由動態光散射粒徑分析儀(DLS)、穿透式電子顯微鏡(TEM)、螢光光譜儀(PL)以及原二色光譜儀(CD)的測定,分析探討本雙親性胺基酸嵌段共聚物在水溶液中自組裝的結構及性質。隨後我們利用雙醣修飾的雙親性胺基酸嵌段共聚物微胞包覆癌症藥物Doxorubicin (DOX)以及進行表面改質礦化,使成為良好的標靶藥物載體,並且透過紫外光-可見光光譜儀(UV)偵測載體內藥物的釋放速率。在未來,我們會進一步研究本實驗製備得到的具有半乳醣基之雙親性胺基酸嵌段共聚物的細胞毒性及細胞吞噬機制。
In the present study, poly(γ-benzyl-L-glutamate)-block-poly(L-phenylalanine) (PBLG-b-PPhe) and poly(γ-benzyl-L-glutamate)-block-polyglycine (PBLG-b -PGly) were synthesized through the ring-opening polymerization (ROP) of N-carboxyanhydrides (NCAs) of the corresponding α-amino acids. The protecting γ-benzyl groups on PBLG block were then removed to give poly(L-glutamic acid) -block-poly(L-phenylalanine) (PLGA-b-PPhe) and poly(L-glutamic acid)-block -polyglycine (PLGA-b-PGly) amphiphilic block copolypeptides. Afterwards, the sugar-containing amphiphilic block copolypeptides self-assembled structures, Lactobionic acid-block-poly(L-glutamic acid)-block-poly(L-phenylalanine) (Lac -b-PLGA-b-PPhe) and Lactobionic acid-block-poly(L-glutamic acid)-block -polyglycine (Lac-b-PLGA-b-PGly), were obtained via Click chemistry:Copper -catalyzed Azide-Alkyne Cycloaddition (CuAAC). The as-prepared amphiphilic block copolypeptides, PLGA-b-PPhe and PLGA-b-PGly can self-assemble to form micelles. With the incorporation of sugar moiety, the micelles can be the targeted drug carriers toward liver cancer cells.
The conformation and structure of the obtained block copolypeptides were characterized by gel permeation chromatography (GPC), Fourier transform -infrared spectroscopy (FT-IR), Differential Scanning Calorimetry (DSC), wide-angle X-ray scattering (WAXS), carbon nuclear magnetic resonance (13C NMR) spectroscopy and proton nuclear magnetic resonance (1H NMR) spectroscopy. The particle size, morphology, and chain conformation of the aggregates in aqueous solutions were determined by transmission electron microscopy (TEM), dynamic light scattering (DLS), and circular dichroism (CD), respectively. Then, we encapsulated doxorubicin (DOX), the drug used in cancer therapy, and mineralized with calcium phosphate to improve the efficacy of the carriers. The drug release from the carriers was evaluated by UV-vis spectroscopy. In the future, the cell cytotoxicity and cellular uptake of the assembled structures used as tumor-targeted carriers for drug delivery will be investigated.
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