結冷膠/阿黴素/胺化石墨烯多功能性肝癌動脈栓塞微粒製備及效能評估

在台灣肝癌死亡率佔據第二名，導管動脈化學栓塞療法是目前肝癌無法切除時的第一線治療，但目前市面上還沒有理想的肝動脈栓塞劑。本實驗以結冷膠為基材，加上胺化石墨烯和阿黴素製備導管動脈化學栓塞試劑，透過乳化法製備微粒。這個系統中結冷膠具備生物相容性且適合做成栓塞劑；胺化石墨烯可以吸附阿黴素和利用物理特性穿透細胞膜。奈米等級的胺化石墨烯是由氧化石墨烯改質而成，氧化石墨烯是透過Hummer’s製備而成。使用雷射粒徑分析儀偵測胺化石墨烯和結冷膠-胺化石墨烯微粒大小分別是1564奈米和200-400範圍之間。掃描電子顯微鏡觀察發現微粒加入胺化石墨烯上表面從光滑變成網狀。在界面電位分析裡可知胺化石墨烯的電位比氧化石墨烯來的正電且胺化石墨烯和阿黴素的結合呈現一個穩定帶正電的狀態，傅立葉紅外線光譜中可知氧化石墨烯確實接上胺基而胺化石墨烯上的胺基和阿黴素產生反應。HepG2細胞可以吸收胺化石墨烯且隨著時間增長吸收量也隨之增長。從藥物釋放數據中得到微粒的藥物釋放符合Higuchi模式。根據上述結果，本研究認為結冷膠-胺化石墨烯-阿黴素是有潛力開發為化學藥物合併栓塞試劑。

Transarterial chemoembolization (TACE) is the first-line treatment at present when liver cancer can’t be cut, but no have the ideal embolic agent currently. In this study we prepared the chemoembolization microsphere (GG/Gra/DOX) composed of gellan gum (GG), graphene (Gra) and anticancer drugs (doxorubicin, DOX) by the emulsification process. In this system, gellan gum with good biocompatibility and suitable as the embolic agent for TACE, grapheme with the function to combinate with DOX and physically penetrate the cell membrane. The nano amine-modifited grapheme is formed by the grapheme-oxide which is made by the Hummer’s method, mixing the ferric chloride, glycol, sodium acetate and ethylenediamine with the high temperature and pressure. The size of nano Gra was 1564nm by the Laser Diffraction Particle Size Analyzer. The size of the microspheres (GG/Gra) were ranged from 200-400 μm by the Laser Diffraction Particle Size Analyzer. The size of microspheres were affected by various gellan gum concentration.The scanning electron microscopefound the surface of microsphere changed from smooth to reticular after adding the Gra. The delta-potential of Gra was positive electricity than GO and Gra mixed DOX was stable in the positive state.The cellular uptake test, found that nano Gra could be uptake into HepG2 cells by endocytosis after co-incubation for 1hr, 3hr , 6hr and 9hr. From these datas, the GG/Gra/DOX microsphere have the potential as the chemoembolization agent in the future.