合成雙性聚二甲基矽氧烷之共聚高分子衍生物：分子特性與生物醫學應用

Abstract

本實驗將甲基丙烯酸分子分散於水中，以自由基光聚合法合成可溶性聚甲基丙烯酸高分子，並與雙末段3-丙基胺之聚矽氧烷形成化學鍵結，合成雙性共聚高分子，PMAA-PDMS。此共聚高分子之化學結構藉由傅立葉轉換紅外線光譜儀、1H-高解析核磁共振光譜儀與質譜儀分析。此雙性共聚高分子具有自組裝特性、可溶性與優異的細胞相容性。此雙性共聚高分子同時具有親水性和疏水性結構，由於在不同溶劑中之親水及疏水作用力不同，在水：酒精體積比為1：1的溶液中，可自組裝形成奈米載體。奈米載體之粒徑大小約為50-100奈米，可由動態光散射粒徑分析儀測得；其形貌可藉由掃描式電子顯微鏡觀察。本實驗採用角膜內皮細胞進行細胞毒性測試，結果顯示此共聚高分子PMAA-PDMS具有十分良好的細胞相容性。 我們進一步將此共聚高分子形成之奈米載體應用於聚2-羥基乙基丙烯酸甲酯水膠系統中，合成一混成載體型複合水膠，探討加入奈米載體對水膠系統之物理性質、細胞相容性及藥物釋放行為的影響。此奈米載體複合水膠的光學性質以紫外光/可見光光譜儀分析。在澎潤度和保水能力方面，因為奈米載體能夠成為水分子擴散的第二層屏障，因而減緩水分擴散，提升複合水膠系統的澎潤度及保水能力。同時，此複合水膠系統也展現出優異的細胞相容性。在藥物釋放行為的探討上，本實驗以多佐胺進行模擬，將藥物包覆進奈米載體並加載於水膠系統。此複合型水膠系統的藥物釋放過程有兩個階段：起初的快速釋放源自於分布在水膠結構間的藥物分子，第二階段則是包覆於奈米載體內部的藥物分子緩慢釋放，因此能有效的減緩藥物釋放速率。簡而言之，此奈米載體具有良好的物理性質及生物相容性，同時具備藥物緩釋能力，在生物醫學方面可應用於載藥型隱形眼鏡或是傷口敷料等。

In this study, an amphiphilic copolymer, polyMAA-PDMS, based on methacrylic acid (MAA) and poly(dimethylsiloxane), bis(3-aminopropyl) terminated, was successfully synthesized. The amphiphilic copolymer, polyMAA-PDMS, has demonstrated capability of self assembly, dissolubility and excellent cytocompatibility. The chemical structure of this amphiphilic copolymer was characterized by Mass Spectrometer, Fourier Transform Infrared Spectroscopy and 1H- Nuclear Magnetic Resonance. Furthermore, when dissolved in a mix solution of ethanol: distilled water =1:1, the amphiphilic copolymer self assembled into nanoparticles because of the differences in solubility between hydrophilic and hydrophobic regimes distributed along the co-polymer chain. The size of spherical nanoparticles is about 50~100nm. The morphology of nanoparticles was examined by Field-Emission Scanning Electron Microscopy (SEM) and Dynamic Light Scattering (DLS). Also, the amphiphilic copolymer shows excellent cytocompatibility toward the BCE cell line, which bring the potentiality for biomedical uses. The co-polymer nanoparticles were loaded into polyHEMA-based hydrogels (termed as NP gel). The optical property of the NP gel was measured by UV-spectrometer. In addition, the NP gel possesses excellent biocompatibility. For the behavior of water retention and swelling ability, the NP gel showed much better water retention capability than pure hydrogel, which is due to the reduction of water diffusion as a result of the presence of the co-polymer nanoparticles. The drug release behavior was tested by loading dorzolamide hydrochloride into the nanoparticles followed by mixing with polyHEMA-based hydrogels. The drug release behavior was measured in-vitro showing a two-stage profile. The first stage of burst release is the release of drugs distributed along with the hydrogels structure while the second one of sustained profile is the release of drugs from within the nanoparticles. In short, this nanoparticle-carrying polyHEMA-based hydrogels showed properties that can be further applied for biomedical uses such as drug-carrying contact lens or advanced wound dressing, over conventional alternatives.