酸鹼高敏感性之兩性幾丁聚醣-聚丙烯酸混摻高分子:分子特性分析、酸鹼應答行為與藥物傳遞之應用

Abstract

由兩性幾丁聚醣與單體丙烯酸,以聚合反應結合並成功地合成出兩性幾丁聚醣-聚丙烯酸分子，且具有在水溶液中自組裝的功能，在溶液中也有良好的分散性。此幾丁聚醣-聚丙烯酸混摻分子藉由FTIR與H1核磁共振儀鑑定其化學結構；而在水溶液中自組裝行為藉由pyrene當偵測試劑並觀察其臨界微胞濃度(critical aggregation concentration )，發現其自組裝的行為與分子在水溶液中的濃度有關。其自組裝形成的奈米的奈米載體之外觀與形貌由穿透式電子顯微鏡(transmission electron microscopy ,TEM)來觀察，其奈米載體在不同酸鹼值下的粒徑大小則由DLS偵測，發現其奈米載體的粒徑大小會隨著環境中的酸鹼呈現變化，而表面電位則經由zeta potentia分析，在酸性環境下帶正電，反之，鹼性環境下則帶負電。此以疏水性藥物CPT為模型進行包覆，達到極佳的包覆率(>90%)。此混摻分子具有良好的生物相容性對於MCF-7。

In this study, amphiphilic chitosan (CHC)–poly(acrylic acid) (PAA) hybrid nanoparticles, which are well dispersed and stable in aqueous solution, have been prepared through polymerization of acrylic acid (AA) in the presence of amphiphilic chitosan (CHC). The chemical structure of the macromolecule was characterized by FT-IR and H1-NMR. The self-assembly behavior of the hybrid macromolecules was characterized through critical aggregation concentration (CAC) measurements which demonstrated a concentration-dependent assembly behavior. Structure morphology of the nanoparticles was investigated using transmission electron microscopy (TEM). Dynamic light scattering (DLS) showed that size of the polymeric micelles at different pH. The zeta potential measurement at different pH showed that the micelles were positively charged at pH 4.5 and negatively charged at pH 7.5.The CHC-PAA nanoparticles were pH responsive in which their mean diameter could change with the pH value of medium. The hybrid macromolecule showed excellent encapsulation efficiency greater than 90% for anti cancer, hydrophobic molecule, (S)-(＋)-Camptothecin. It’s outstanding cytocompatibility towards the MCF-7 cell line, associated with its structural stability under diluted condition, suggest a promising nanocarrier for drug delivery application.