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標題: | 以幾丁聚醣/褐藻酸奈米粒子做為阿莫西林載體根除幽門螺旋桿菌 Chitosan alginate nanoparticles as amoxicillin delivery vehicle for eradication of Helicobacter pylori |
作者: | Yuan-Ting Chang 張媛婷 |
指導教授: | 謝銘鈞(Ming-Jium Shieh) |
關鍵字: | 幾丁聚醣,褐藻酸,阿莫西林,幽門桿菌, chitosan,alginate,amoxicillin,H. pylori,mucoadhesion, |
出版年 : | 2012 |
學位: | 碩士 |
摘要: | 於1982年,Warren和Marshall 證實了胃中確實存在一株革蘭氏陰性細菌-幽門桿菌,經過十幾年的研究發現這株細菌的存在會是導致消化性潰瘍的主要致病因素。目前使用的抗生素種類包括阿莫西林(amoxicillin)、甲硝唑(metronidazole)、四環素類(tetracycline),在體外細胞實驗中這些抗生素均能有效的毒殺幽門桿菌,但在臨床的治療上卻無法達到完全的根除效果。而造成的原因有因為抗生素在胃酸的環境下會快速地被降解、再者是因為抗生素本身滲透進入黏膜層的能力較差。因此結合以上種種的因素會使抗生素濃度無法在幽門桿菌感染區域達到最低有效抑菌濃度。部分研究指出奈米化載體因尺度小能提升藥物滲透黏膜的能力。而阿莫西林需在接近中性的pH環境下才可發揮最好的藥效,文獻指出在體外試驗中發現阿莫西林活性在pH從3.5增加到5.5時可增加10倍。
幾丁聚醣與褐藻酸均是具有生物相容性生物性降解能力的聚醣類高分子,而部分研究指出此兩種高分子材料均具有黏膜吸附特性尤其是幾丁聚醣。因此這兩類天然性高分子被廣泛運用於藥物載體的研發。 結合以上這些問題,我們希望利用幾丁聚醣與褐藻酸做為包覆阿莫西林之載體以達到在胃中黏附於黏膜層上同時有暫緩阿莫西林被胃酸的破壞並做藥物釋放直接抑制幽門桿菌生長。經由初步動物實驗結果證實以藥物濃度相關性條件實驗中,此奈米藥物在兩個禮拜的治療時間內藥物濃度降低為一般臨床用藥的十分之一仍然有約90%治療率。而在單純餵食載體的組別中其幽門桿菌的治療率仍有約90%以上。另外在時間相關性條件實驗中發現在經五天的治療實驗下濃度為一般臨床用藥仍有約80%治療率。此外餵食標記螢光分子的奈米藥物實驗中,在螢光系統觀察下發現單純的阿莫西林在胃中的訊號只維持到6小時,而相對奈米載體可在胃中滯留到12小時,並可發現此載體會隨時間而被細胞吞噬。而於Isotope實驗中發現標有123I的阿莫西林在位中的訊號能維持到6小時,而相較於奈米載體卻可在胃中滯留到24小時之久。因此從目前的實驗結果均顯示此奈米藥物確實有延長滯留於胃中之能力且同時具有毒殺幽門桿菌能力,勢必能成為毒殺幽門桿菌之新型藥物。 In 1982, Warren and Marshall proved that a Gram-negative microorganism, Helicobacter pylori (H. pylori), is the key etiological factor causing peptic ulcer. Many antibiotics, such as amoxicillin, metronidazole, and tetracycline, are effective in treating H. pylori in vitro but are ineffective in the in vivo treatment. The failure of these antibiotics used in vivo has been attributed to the rapid destruction of the antibiotics in the acidic gastric condition, poor permeation of across mucus layer and the associated difficulty of reaching the minimum inhibitory concentration of H. pylori. Some papers showed that nanoparticals have the ability to penetrate mucus and be a drug delivery vehicle for completing eradication of H. pylori which colonised deeply into the gastric mucosal lining. Chitosan and alginate are biocompatible and biodegradable polysaccharides, some literatures showed that they both have mucoadhesive property, especially chitosan. Therefore, these two polymers have been widely used for developing drug delivery systems. To overcome the problems mentioned above, the main goal of our study is to develop amoxicillin containing nanoaparticles that could protect encapsulated amoxicillin in the gastric acid environment and interact with the local site of H. pylori infections. The in vivo fluorescence-microscopic and isotope computed-tomographic results demonstrate that this nanoparticles can adhesion in gastric for long time. This work presented that in in vivo study the dosage decreasing to one tenth had achieved therapeutic efficacy. The group presented that treatment of chitosan/alginate nanoparticles without amoxicillin has also display therapeutic efficacy. By the way when decrease treatment time also have good therapeutic efficacy. Those results indicated that chitosan/alginate containing amoxicillin nanoparticles may provide a delivery system for the efficient eradication of H. pylor. |
URI: | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/15849 |
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