藥物奈米載體於治療胃潰瘍之應用: 體外與體內實驗

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題名:	藥物奈米載體於治療胃潰瘍之應用: 體外與體內實驗
作者:	林宥欣(Yu-Hsin.Lin);賴志河(Chih-Ho Lai)
貢獻者:	生命科學院生物科技學系
日期:	2014-07-31
上傳時間:	2012-06-13 10:52:35 (UTC+8)
摘要:	胃潰瘍為一種普?消化系統疾病，研究得知，胃幽門?旋桿菌寄居黏膜上皮細胞引發胃潰瘍疾病。?床上常用抗生素?對抗胃幽門?旋桿菌，由於使用藥物常須持續一段長時間，?導致引起服用藥物的病人會有頭?、腹瀉、過敏等副作用和抗藥性胃幽門? 旋桿菌種種問題。同時，當胃幽門?旋桿菌感染胃壁細胞時，所分?毒素影響細胞間隙蛋白質結構，引起胃壁細胞嚴重發炎和胃癌危險。本研究室先前計畫補助下，採用酸鹼敏感性水膠和?米載體針對胃幽門?旋桿菌研究，研究成果成功發表?篇國際期刊 [2009? Biomaterials (IF 7.365) 和 2010? Biomacromolecule (IF 4.502) ]。本研究為?讓所製備?米載體達到?具有?床應用性，今?申請三?期計畫中，擬形成一可標靶胃幽門桿菌和具備包覆黃?素與抗生素能?的藥物?米載體，應用在胃潰瘍?鼠治?。第一 ?建?高標靶性和包覆藥物褐藻?-幾丁聚醣/肝素?米載體技術平台，探討物化性質和細胞標的情況。第二?延續包覆藥物結果?抑制胃幽門?旋桿菌，探討藥物?米載體對抑制胃幽門?旋桿菌感染細胞情況，分析?米載體與胃幽門?旋桿菌在細胞間相關蛋白影響。第三?動物實驗，?用胃潰瘍?鼠測試標靶性藥物?米載體在活體藥物傳遞和活體影像觀察，期待所形成標靶性藥物?米載體?具?床應用性。 Gastric ulcer disease represents a worldwide health problem because of its high morbidity and mortality. Helicobacter pylori is considered to be an important etiological factor in gastric ulcer disease and has been suggested as a cause of gastric carcinoma. Moreover, H. pylori colonizes the human gastric mucus layer and adheres to the surface epithelial cells by virtue of a variety of adhesin-like proteins. In order to effectively eradicate H. pylori infection, the therapeutic agent must be able to penetrate through the gastric mucus layer and maintain a concentration sufficient for antibacterial activity at the infected site for a suitable length of time. The most widely recommended regimen includes a triple therapy which combines various antibiotics (amoxicillin, clarithromycin, and metronidazole) and a proton pump inhibitor administered over a period of two weeks. However, the occurrence of unpleasant side effects, such as a metallic taste in the mouth, diarrhea and nausea, may cause the patient to interrupt the prescribed course of antibiotics, thus promoting the development of bacterial resistance. In our reported research (2009 Biomaterials; IF. 7.365 and 2010 Biomacromolecule; IF. 4.502), pH-responsive hydrogels and pH-sensitive nanoparticles were produced to allowing them to protect an incorporated drug from destructive gastric acids. We also demonstrated that the prepared nanoparticles can adhere to and infiltrate cell–cell junctions and cell nuclei. In the study, a platform technology in developing anti- H. pylori drug (amoxicillin and berberine) incorporated in nanoparticles composed of fucose-chitosan and heparin is proposed for eradication of targeting H. pylori. Each of the three sub-studies in this project will be designed as per the research experience and expertise obtained during this project. The targeting H. pylori nanoparticles composed of fucose-chitosan and heparin will be developed drug (amoxicillin and berberine) will be incorporated in nanoparticles, and its physicochemical characteristics, and cellular uptake nanoparticles will be analysis by confocal laser scanning microscopy (1st year). The fluorescent probe will conjugate at antibiotic and a loaded drugs nanoparticle carriers, which can suppresses the stomach H. pylori growth ability will be study. And the human gastric adenocarcinoma cell protein immunity fluorescence staining technique analysis will be established (2nd year). The study will be designed for targeting H. pylori nanoparticles studying for clinical reach. The animal living study fliorescence analysis, using IVIS 200 will be developed and the nanoparticles will be designed for targeting H. pylori studying in vivo gastric ulcer mice mode for clinical reach.
顯示於類別:	[生物科技學系暨碩士班] 研究計畫

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