近年來口腔癌的發生率攀升到十大癌症之第六位，其死亡率已節節上升超過了鼻咽癌，成為國人頭頸部癌症的第一位。口腔癌術後出現明顯復發率，使得近年來研究多著重於尋找口腔癌的替代療法。薑黃素是由Curcuma longa L.之根莖中所分離出來的主要成分，具有抗腫瘤、抗發炎、免疫調節等藥理活性，可誘導癌細胞的凋亡。然而薑黃素之溶解度及生體可用率均不佳，近年來之研究大多利用各種不同遞藥系統以提高其生體可用率。
幾丁聚醣為天然的多醣類高分子，具有生物相容性、生物可分解性等特性。本研究合成之兩性乙二醇幾丁聚醣是由親水性的乙二醇幾丁聚醣架接不同碳鏈長度的脂肪酸(palmitic acid、lauric acid)，得到同時具有親水與親脂性的palmitoyl glycol chitosan(GCP)、 lauroyl glycol chitosan(GCL)，並利用酸水解的方式，得到低分子量的LMWGCP與LMWGCL。本研究之目的在探討以四種兩性乙二醇幾丁聚醣做為薑黃素口腔局部輸藥載體之可行性。
研究結果顯示四種兩性乙二醇幾丁聚醣(GCP、GCL、LMWGCP、LMWGCL)皆不影響薑黃素對於口腔癌細胞之細胞毒性，為安全性高的聚合物載體。四種兩性乙二醇幾丁聚醣之薑黃素處方中以低分子量且鍵結lauric acid的LMWGCL之釋出速率(1.83±0.05μg/h cm2)以及分佈於倉鼠頰膜上的組織濃度 (epithelium : 582.78±9.99μg．hr/g) 最高。當兩性乙二醇幾丁聚醣濃度增加時，薑黃素溶解度亦隨之增加，但釋出速率與頰膜組織濃度都隨之降低，可能與黏度增加以及滲透速率降低有關。與HPMC、CMC-Na相較，兩性乙二醇幾丁聚醣可減少薑黃素進入全身循環，而降低全身性副作用，體內試驗結果亦顯示LMWGCL具有高度的腫瘤親合性與穿透性。
綜合研究結果，四種兩性乙二醇幾丁聚醣中以低分子量且架接短鏈lauric acid 的LMWGCL 具有較佳的薑黃素釋出速率和頰膜組織穿透能力，對於頰膜之Epithelium和Lamina propria具選擇性，且可減少薑黃素進入全身循環，有較佳的局部作用特性及高腫瘤組織穿透性，對於口腔癌治療的應用值得進一步探討。

In recent years, the incidence of oral cancer is rising to the sixth of all the cancers, and its mortality has become the leading cause of head and neck cancers. Surgical treatment of oral cancer usually comes with high recurrent rate, and a number of studies have been focused on alternative therapy. Curcumin is the major compound derived from the rhizomes of Curcuma Longa L., which has anti-neoplastic, anti-inflammatory, and immuno-modulatory acitvities, and may induce apoptosis in tumor cells. Many studies have investigated various curcumin delivery systems to improve its solubility and bioavailability.
Chitosan is a natural polymer, with features of bio-compatibility and bio-degradability. Palmitoyl/Lauroyl glycol chitosans (GCP/GCL) are obtained by modifying hydrophilic glycol chitosan with fatty acids (palmitic acid or lauric acid). In addition, glycol chitosan of lower molecular weights was prepared by acidic degradation and further modified with palmitic and lauric acid to form low molecular weight GCP/GCL (LMWGCP/LMWGCL). The objective of the study was to evaluate the feasibility of the four amphiphilic glycol chitosans as topical delivery carrier of curcumin to oral mucosa.
In vitro experiments demonstrated that the four amphiphilic glycol chitosans did not affect the cytotoxicity of curcumin on oral cancer cells. The release and tissue distribution of curcumin in Syrian Hamster cheek pouch were the highest from LMWGCL, namely, 1.83 ± 0.05 μg/h cm2 and 582.78±9.99 μg．hr/g (epithelium), respectively. When LMWGCL/GCP concentrations were increased, curcumin solubility was elevated, while release rate and tissue distribution were decreased, presumably due to the increase in viscosity and permeation rate. In comparison with commercially available HPMC and CMC-Na, amphiphilic glycol chitosans showed lower absorption of curcumin. It was also observed in vivo that curcumin permeability into tumor cheek pouch was higher from LMWGCL.
In summary, LMWGCL demonstrated optimal curcumin release and pouch distribution, reduced absorption, and tumor permeability. The results warrant further investigation on its application to topical delivery of curcumin for the treatment of oral cancer.

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黃彥凌 兩性幾丁聚醣凝膠作為維他命C磷酸鎂鹽經皮傳輸載體之評估。
國立成功大學臨床藥學研究所，碩士論文，2008