藉由可調控氫鍵作用力控制具環境刺激響應高分子於藥物釋放之應用

Abstract

本篇論文是在研究藉由多點式互補氫鍵的分子識別方式，建立出具刺激響應能力的超分子系統，並探討其在藥物釋放之應用。首先，我們以開環聚合和點擊化學的方式合成出poly(εCL-g-Uracil)並將poly(propylene glycol)的雙邊末端改質成adenine，透過adenine和uracil間的多點式互補型氫鍵作用力架構出我們的雙親性超分子共聚物。 由U-PCL:A-PPG-A系統自組裝而成的微胞在水中具有良好的穩定性，利用非共價鍵作用力的超分子系統對環境敏感的特性，我們可在弱酸的環境下使得微胞的結構瓦解。藉由此特性我們利用pyrene作為疏水性藥物，對於微胞在pH=5時的弱酸環境條件下觀察了我們的微胞系統對於藥物釋放的行為。另外，透過酵母細胞的培養實驗可以發現我們的材料並不具有明顯的生物毒性，代表在生醫材料相關領域的研究或應用上是具有高度的發展潛力。因此，由實驗觀察的結果顯示，我們透過互補型氫鍵作用力所形成的超分子系統於藥物釋放之領域是一良好的研究題材。

Novel supramolecular copolymer micelles with stimuli-responsive abilities were successfully prepared through the complementary multiple hydrogen bonds of nucleobases and then applied for rapid release of drugs. First, a series of biomimetic copolymers, poly(εCL-g-Uracil)were synthesized through combination of sequential ring-opening and click chemistry, then we synthesized adenine-terminated poly(propylene glycol) (A-PPG-A). The supramolecular amphiphilic copolymers (U-PCL:A-PPG-A) were formed based on multiple hydrogen bonding interactions between U-PCL and A-PPG-A. The micelles selfassembled from U-PCL:A-PPG-A were sufficiently stable in water but tend to fast aggregation in acidic condition due to the sensitive nature of noncovalent interactions. The low cytotoxicity of supramolecular copolymer micelles was confirmed by incubation of living yeast cell. As a hydrophobic anticancer model drug, pyrene was encapsulated into the supramolecular copolymer micelles. In vitro release studies demonstrated that the release of pyrene from micelles was fast at mildly acid pH of 5.0. Therefore, this supramolecular system based on the complementary multiple hydrogen bonds of nucleobases is very promising candidate for rapid controlled release of drugs.