結冷膠/透明質酸薄膜包覆Clioquinol及5-fluorouracil作為口腔癌治療貼片之研究

口腔癌為發生在口腔的惡性腫瘤之總稱，一般多以手術、放射線及化學藥物進行治療。為了達到術後傷口癒合及防止口腔癌復發，我們將治療藥物包覆在基材中作為口腔癌治療貼片，以一種非侵入性的治療方式覆蓋於病灶處。本研究利用結冷膠 (Gellan gum ; GG)結合透明質酸(Hyaluronic acid ; HA) (GH)研製出具有降解性的薄膜，基於文獻指出Clioquinol (CQ)及5-Fluorouracil (5-FU)的抗癌機轉可應用於口腔癌治療，因此我們分別將這兩種不同性質的藥物包覆於薄膜，並進一步探討薄膜機械性質、藥物釋放動力學、半致死劑量(IC50)及體內外研究。研究結果顯示，經交聯作用後的結冷膠薄膜 (GG)及結冷膠透明質酸混合薄膜(GH)之含膠量分別為87.35%及84.5%；而含水量分別為82.78%及88.54%。FTIR結果顯示薄膜交聯前後的訊號有差，但藥物不影響交聯作用。拉伸試驗結果為GH薄膜機械強度較GG薄膜來得強，分別為3.1±0.1kgf及2.8±0.07kgf。GG/CQ及GH/CQ薄膜釋放率皆為40%；GG/5FU及GH/5FU薄膜釋放率分別是17%及12%。最後以動物模式進行評估。

Oral cancer is the general term that describes a malignant cancer of oral, the most of oral cancer are belong to squamous cell carcinoma, which can appear in any part of the oral cavity. The common seen treatment of oral cancer are surgery, radiation and chemical drugs. In order to achieve the postoperative wound healing and prevent the recurrence of oral cancer, we used anti-cancer drugs coating in our base material as a non-invasive oral cancer treatment patch. In this study, we used gellan gum (GG) and hyaluronic acid (HA) compound (GH) as a base material to prepare a degradability film, furthermore based on the anti-cancer mechanism of clioquinol (CQ) and 5-fluorouracil (5-FU) from literatures, which can applied on oral cancer treatment, then we will investigated the mechanical properties, drug release kinetic, inhibitory concentration (IC50), in vitro and in vivo studies. The gel content results of GG film and GH film are 87.35% and 84.5%, respectively; water content results are 82.78% and 88.54%, respectively. FTIR shown the signal have discrepancy between before and after cross-linking, but the drugs did not have an effect on cross-linking. The mechanical properties shown GH films more stronger than GG films，are 3.1±0.1kgf and 2.8±0.07kgf, respectively. The accumulative release of GG/CQ and GH/CQ film are 40%, whereas GG/5FU and GH/5FU films are 17% and 12%, respectively. Finally, we evaluate the film by set up animal model.