- 學位論文
結腸直腸癌治療藥物之奈米載體應用研究
Development of Therapeutic Nano-carrier and potential Application for Colorectal Cancer therapy
摘要
結腸直腸癌在全世界佔有相當的罹患率和死亡率。其病因開始都是由許多微小非癌性的adenomatous polyps，隨著時間有些polyps逐漸轉變為癌細胞。本研究目標為排除這樣早期的非癌性polyps，去停止細胞癌化的發展。 Curcumin (薑黃素)主要是一種黃色原料，存在於薑黃(Curcuma longa)的植物之中，近來的研究證實，curcumin具有效的抗癌及抗發炎的活性。 本研究要將curcumin當作model藥物，設計一局部治療結腸直腸癌的nano-emulsion處方。Nano-emulsion可以改善水難溶性curcumin的溶解度，且能讓curcumin在治療結腸直腸癌方面，有效增加curcumin的作用。在發展製備nano-emulsion處方中，以Poloxamer 188選為我們適合的界面活性劑、ethanol當作油相及輔助界面活性劑。研究中探討的nano-emulsion處方，droplet size皆小於100 nm，polydispersity index都低於0.7。體外穿透黏膜的試驗中，隨著增加nano-emulsion處方中Poloxamer 188的量、也提升其黏膜穿透率。在體外黏膜內藥物含量的試驗中，於我們設計的處方發現，當Poloxamer 188含量較低時，於24小時後黏膜內藥物含量是比較高的。利用MTT assay去測試curcumin (O/W) nano-emulsion對於colon cancer cells的細胞毒殺效果，結果發現curcumin (O/W) nano-emulsion 抑制colon cancer cells具有concentration和time dependent的情形。
並列摘要
Colorectal cancer is responsible for substantial mortality and morbidity in the world. It has been known to begin mostly as small and non-cancerous adenomatous polyps. Over time, some of these polyps become tumorgensis. The objective of this MSc research seeks to develop means to eliminate the precancerous polyps, while stopping the propagation of tumorgensis. Curcumin is a major yellow pigment in turmeric (Curcuma longa) and is widely used as a popular spice around the world. Recent studies have demonstrated that curcumin exerts strong anti-carcinogenic and anti-inflammatory activities. This series of studies have been designed to develop a therapeutic nano-emulsion formulation to achieve a localized delivery of curcumin, as the model drug, to the colorectal mucosa. Nano-emulsion is expected to improve the solubilitzation of poorly water-soluble curcumin and thus expected to increase its effectiveness in the chemoprevention of colorectal cancer. In the formulation development of nano-emulsion, Poloxamer 188 was found to be an applicable surfactant while ethanol was added as a co-surfactant and also as the oil phase. The formulation had achieved a particle size of under 100 nm, polydispersity of lower than 0.7. In transmucosal permeation study, the permeation profiles demonstrated that the mucosa flux of Poloxamer 188 increased as amount increasing in vitro. In mucosa uptake kinetics test, the mucosa curcumin amount in 24 hours demonstrated that nano-emulsion of Poloxamer 188 decreased as amount of curcumin in mucosa increasing. We found a nano-emulsion formulation that was low permeability and high amount of drug in colon mucosa at 24 hours. The cytotoxicity of the curcumin (O/W) nano-emulsion on the human colon cancer cells was evaluated by the MTT assay. Curcumin (O/W) nano-emulsion inhibited the cell growth of colon cancer cells in a concentration- and time-dependent manner.
參考文獻
延伸閱讀
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