生物資源暨農學院: 食品科技研究所指導教授: 蔣丙煌徐鴻文Hsu, Hong-WenHong-WenHsu2017-03-032018-06-292017-03-032018-06-292016http://ntur.lib.ntu.edu.tw//handle/246246/273919EGCG是茶葉中含量最豐富的兒茶素，具有改善肥胖和代謝症候群的能力，而最近的研究顯示EGCG還具有抑制大腸直腸癌增生以及調降免疫抑制酵素indoleamine 2, 3-dioxygenase(IDO)表現的能力，因此被認為具有應用在癌症免疫療法上的潛力。然而EGCG在腸道的環境中會被快速的氧化成巨分子或是被微生物代謝成小分子，所以難以抵達大腸並被直腸癌細胞吸收。為了改善其消化穩定性，本研究選用微脂體包埋的方式來減少周圍環境對EGCG影響，另外本研究希望作為藥物載體的微脂體能提升癌細胞對EGCG的吸收能力，所以將利用細胞癌化過程中會改變表面電位以及增加胞吞作用的兩個特性，探討帶有不同表面電位以及流動性的微脂體對癌細胞的影響。然而使用微脂體作為載體時，需要注意腸道中的酯解酶會使藥物過早釋出，而本研究將使用溶解度會隨酸鹼值變化的聚合物來包埋微脂體，以避免藥物載體與酵素的接觸。在EGCG吸收率的實驗結果顯示，微脂體能提高癌細胞對EGCG的吸收能力，流動相的微脂體其藥物吸收率顯著高於膠體相，當微脂體帶有正表面電位時，其藥物吸收率高於帶負電以及中性表面電位，且當表面電位越高時其藥物吸收率越好。在物理性質上，流動相微脂體具有較高的包覆效率以及較小的平均粒徑，而在濕式的儲存條件中，各式微脂體均無法防止EGCG擴散出去，但大致能維持住表面電位的穩定性，而幾丁聚醣包覆的微脂體是例外。在包材模擬消化的過程中，發現同時有溶解度隨酸鹼值變化以及緩慢釋放特性的包材較能在模擬大腸消化的後期完全溶解，具有將藥物控制釋放在大腸部位的潛力。EGCG is a polyphenol which has been well known for its potential to affect human health and disease such as obesity and matabolic syndrome. Recently, some researches suggest that EGCG can inhibit the proliferation of colorectal cancer cells and the expression of indoleamine 2, 3-dioxygenase(IDO) which is an immunosuppresive enzyme. Thus, EGCG can be considered as a potential agent for antitumor immunotherapy. However, ECGC would be rapidly oxidized and broken down into small compounds in intestinal tract. Thus, it is different to reach colon and be absorbed by colorectal cancer cells. To improve its digestion stability, we will encapsulate EGCG into liposome to prevent it from oxidation and hydrolysis catalyzed by enzymes. In addition, we plan to make our drug carriers selectively deliver EGCG to colon cancer cells. Because the surface charge of cancer cells will become more negative due to aberrant sialylation in the progress of cancerization, we can use cationic liposomes as drug carriers to increase its selectivity. There are some factors which will affect this selectivity such as the level of surface charge, the charge mobility and the membrane fluidity of drug carriers. So, we will go deep to investigate their effects on the selectivity of drug delivery. However liposomes cannot protect EGCG in intestinal tract because of lipases, we need to further encapsulate liposomes into pH responsive materials to avoid premature drug release. In our cellular drug uptake experiments, we find liposome can enhance drug delivery efficiency. Fluid phase liposomes have more drug deliver efficiency than gel phase and positive surface potential liposomes can deliver more drug than neutral & negative surface potential liposomes during the same period. But, if liposomes have high positive surface potential, gel phase liposome can deliver more drug than fluid phase liposome. We also evaluate the physicochemical characterizations of different liposomes and find fluid phase liposomes have better encapsulation efficiency and small average size. However, liposomes can not keep inside of EGCG in wet preservation but some of them can still keep their surface potential. In coating material dissolution experiments, we find that coating material need to have pH-responsive solubility and sustained release properties to help them to deliver drug to large intestine.4619946 bytesapplication/pdf論文公開時間: 2016/8/24論文使用權限: 同意有償授權(權利金給回饋學校)EGCG大腸直腸癌消化穩定性微脂體表面電位colonrectal cancerdigestion stabilityliposomesurface potential[SDGs]SDG3thesis10.6342/NTU201602053http://ntur.lib.ntu.edu.tw/bitstream/246246/273919/1/ntu-105-R03641016-1.pdf