Please use this identifier to cite or link to this item: http://hdl.handle.net/11455/3851
標題: 溫度/酸鹼應答型接枝高分子與Doxorubicin形成複合微胞之製備與性質探討
Preparation and Characterization of Complex Micelles from Thermo/pH-Responsive Graft Copolymers with Doxorubicin
作者: 黃信憲
Huang, Hsin-Hsien
關鍵字: Complex Micelles
應答型高分子
Doxorubicin
微胞
出版社: 化學工程學系所
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摘要: 在本研究中,以自由基聚合法製備poly(NAS-co-MEA)做為高分子的主鏈,poly(N-isopropylacrylamide) (PNIPAAm)與monomethoxypoly(ethylene glycol) (mPEG)做為接枝側鏈,得到具備溫度/酸鹼應答型的雙性接枝高分子poly(NAS-co-MEA)-g-PNIPAAm/mPEG。此溫度/酸鹼應答型之雙性接枝高分子的主鏈上帶有羧酸官能基(-COOH),當pH值大於pKa時,多數會成為游離型態的-COO-,將吸引帶相反電荷的Dox藥物分子,藉由靜電作用力形成疏水微胞核心,而接枝高分子的親水側鏈PNIPAAm和mPEG則在核心週圍形成親水層,成為微胞型態,隨後給予加熱以及交聯,穩定此複合微胞(complex micelles)的結構。當升溫到60℃時,PNIPAAm轉為疏水性鏈段,向微胞內疏水核心聚集,藉此作用力使得微胞核心結構更為紮實,Dox堆疊的更為緊密穩定,在低溫4℃下可以保存近一個月而無變化。而由DLS、1H-NMR與TEM的結果顯示,由接枝高分子與Dox形成的複合微胞是穩定紮實的奈米粒子,並不會隨溫度的變化而產生明顯的變化。在藥物釋放實驗中,此複合微胞釋放Dox的行為與pH值有關,在pH 4.7的環境下,由於主鏈上的AAc單元開始質子化,帶負電荷基團逐漸消失,與Dox間的靜電作用力破壞,而無法再維持核心的結構,使得Dox釋放出來;在pH 7.4或6.3的環境下,由於AAc單元解離的程度不會有明顯變化,而能維持構成核心的靜電作用力,由藥物釋放實驗的結果呈現,在一開始的burst release後,complex micelles的Dox釋放量維持在一定的水平。
In this study, temperature and pH-responsive graft copolymer which comprising acrylic acid (AAc) units and 2-methacryloylethyl acrylate (MEA) units as the polymeric backbones and poly(N-isopropylacrylamide) (PNIPAAm) and monomethoxypoly(ethylene glycol) (mPEG) as grafts were synthesized. The formation mechanism and characterization of micelles from complexes between the negatively charged carboxyl groups of the graft copolymers poly(AAc-co-MEA)-g-PNIPAAm/mPEG, and the cationic drug, doxorubicin (Dox), were investigated. The positive charge of Dox molecules at pH 7.4 provided the driving force for binding with negatively charged carboxyl groups on backbones by electrostatic interaction. The Dox/AAc complex cores surrounded with hydrophilic nonionic PNIPAAm and mPEG shell which illustrated the morphological structure of micelles. The complex micelles were subsequently stabilized by heating and cross-linked. The results of dynamic light scattering (DLS), 1H-NMR and transmission electron microscopy (TEM) experiments illustrate that the complex micelles are stable and compact nanoparticles. The structure of the complex micelles can be maintained at 4℃ up to one month. In the drug release experiments, Dox release from the complex micelles that was a pH-dependent process. The protonation of carboxyl groups at a mildly acidic condition resulted in an accelerated release of Dox at pH 4.7 compared to pH 7.4.
URI: http://hdl.handle.net/11455/3851
其他識別: U0005-2907201015510100
文章連結: http://www.airitilibrary.com/Publication/alDetailedMesh1?DocID=U0005-2907201015510100
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