生物資源暨農學院: 食品科技研究所指導教授: 蔣丙煌張秀銀Udompornmongkol, PanisaPanisaUdompornmongkol2017-03-032018-06-292017-03-032018-06-292015http://ntur.lib.ntu.edu.tw//handle/246246/273937大腸癌是全球主要致死成因之一，近年來有研究指出萃取自薑黃（Curcuma longa）根莖部的薑黃素（curcumin）具有抗大癌的潛力。然而，雖然薑黃素在疾病治療上具有龐大潛力，但其功效在經口攝食後會因為受到其在消化系統中的腸胃道移動率（gastrointestinal motility）與酸鹼值而有所受限，而利用某些具生物降解性特質的材料發展釋控系統（controlled release system）可能可以克服上述問題。若這個系統具有可專一性地被存於大腸中特定菌相的酵素水解，則可將薑黃素送到大腸以發揮其抗大腸癌之功效。此外，奈米粒子（nanoparticles）在釋控系統中的應用性亦受到廣泛探討。因此，本研究的目的是製造一高分子奈米粒子作為藥物載體，而利用此載體裝載薑黃素，藉以提升其抗大腸癌活性。本研究首先使用幾丁聚醣（chitosan）、阿拉伯膠（gum arabic）與天然多糖作為載體材料，而後利用乳化溶液擴散法（emulsification solvent diffusion method）製備奈米粒子載體，接著使用傅立葉轉換紅外光譜（fourier transform infrared spectroscopy）與熱差掃描卡計（different scanning calorimeter）確立奈米粒子的形成情況。結果顯示薑黃素確實被包覆於載體中，其zeta電位為+48 mV、粒子大小為136 nm，並具有95%的高包覆率（encapsulation efficiency）。同時，體外釋放試驗（in vitro release study）的結果顯示，當經奈米載體包載的薑黃素浸潤於含有果膠酶（pectinase）的大腸液模擬溶液後，會有76%的薑黃素釋放出來。我們藉此推測此包載薑黃素的奈米粒子對於胃液或小腸酵素的水解具有耐受性，而可完整無缺地到達大腸。另外，在與人類大腸癌細胞株（包括HCT116、HT29與LOVO）相關的細胞實驗中，我們發現相較於未經包載的薑黃素，經本研究組合成之奈米載體包載的薑黃素會因為具有較高的細胞攝入效率，而有較佳的抗大腸癌特性。我們更進一步探討其相關的機制，結果發現未經包載的薑黃素主要可使大腸癌細胞產生細胞週期停滯現象（cell cycle arrest），而使細胞週期停留於S期或G2/M期；然而，經奈米載體包載的薑黃素則可誘發細胞凋亡（cell apoptosis）。因此，綜合上述可知，以幾丁聚醣和阿拉伯膠構成的奈米粒子包載薑黃素，確實有較佳的抗大腸癌效果。Colorectal cancer (CRC) is one of the top leading causes of death in the world. Recent studies have shown that curcumin, a yellow polyphenol extracted from the rhizome of turmeric (Curcuma longa) has potent anti-colorectal cancer effect. Despite great therapeutic potentials of this phytochemical in CRC, their performance, after oral intake, may be limited by gastrointestinal (GI) motility and pH variations in the digestive system. Hence, there is strong need to develop a controlled release system for protecting curcumin passing through the digestive system and reaching the colon site. Such system takes advantages of the fact that some specific microbial enzymes, which can hydrolyze the biodegradable materials, only exist in the colon. Since, nanoparticles have received a great deal of attention for their usefulness in the controlled release system, the purpose of this research was to fabricate polymeric nanoparticles as drug carriers for encapsulated curcumin with enhanced anti-colorectal cancer activities. Nanoparticles were formed using chitosan and gum arabic, natural polysaccharides, via an emulsification solvent diffusion method. The formation of curcumin nanoparticles was confirmed by fourier transform infrared (FTIR) spectroscopy and differential scanning calorimeter (DSC). The results showed that curcumin was entrapped in carriers with +48 mV, 136 nm size, and high encapsulation efficiency (95%). Based on an in vitro release study, 76% of curcumin was released from nanoparticles after immersing into simulated colonic fluid containing pectinase. We inferred that the curcumin nanoparticles could tolerate hydrolysis due to gastric juice or small intestinal enzymes, and therefore, it should reach the colon largely intact. The cell culture studies with human colorectal cancer cell lines; HCT116, HT29 and LOVO cells revealed that curcumin nanoparticles had higher anti-colorectal cancer properties than the free curcumin due to greater cellular uptake even at low concentration (1 µg/mL). In addition, curcumin nanoparticles could induce cell apoptosis while free curcumin showed cell cycle arrest at S and/or G2/M phase. Therefore, we concluded that curcumin was successful encapsulated in chitosan-gum arabic nanoparticles with superior anti-colorectal cancer properties.8078464 bytesapplication/pdf論文公開時間: 2015/8/25論文使用權限: 同意有償授權(權利金給回饋學校)大腸癌薑黃素釋控系統奈米粒子幾丁聚醣阿拉伯膠Colorectal cancerCurcuminControlled releaseNanoparticlesChitosanGum arabic[SDGs]SDG3thesishttp://ntur.lib.ntu.edu.tw/bitstream/246246/273937/1/ntu-104-D99641009-1.pdf