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用于口腔癌治疗贴片的结冷胶/葡萄糖胺/氯碘羟喹膜的制备与表征

Preparation and characterization of gellan gum/glucosamine/clioquinol film as oral cancer treatment patch.

作者信息

Tsai Wanchi, Tsai Huifang, Wong Yinuan, Hong Juiyen, Chang Shwujen, Lee Mingwei

机构信息

Department of Medical Laboratory Science and Biotechnology, Kaohsiung Medical University, Taiwan.

Department of Medical Laboratory and Biotechnology, Chung Shan Medical University, Taiwan.

出版信息

Mater Sci Eng C Mater Biol Appl. 2018 Jan 1;82:317-322. doi: 10.1016/j.msec.2017.05.040. Epub 2017 May 11.

DOI:10.1016/j.msec.2017.05.040
PMID:29025664
Abstract

To administer cancer drugs with improved convenience to patients and to enhance the bioavailability of cancer drugs for oral cancer therapy, this study prepared gellan gum/glucosamine/clioquinol (GG/GS/CQ) film as the oral cancer treatment patch. GG/GS/CQ film fabricated through the EDC-mediated coupling reactions (GG/GS/CQ/EDC film). The film of the physicochemical properties and drug release kinetics were studied. The effectiveness of GG/GS/CQ/EDC film as oral cancer treatment patch were evaluated with the animal model. The results confirmed that CQ can be incorporated via EDC-mediated covalent conjugation to gellan gum/glucosamine. Mechanical testing revealed that the maximum tensile strength and elongation percentage at break were 1.91kgf/mm and 5.01% for GG/GS/CQ/EDC film. After a drug release experiment lasting 45days, 86.8% of CQ was released from GG/GS/CQ/EDC film. The Huguchi model fit the GG/GS/CQ/EDC drug release data with high correlation coefficients (R=0.9994, respectively). The effect of the CQ dose on oral cancer cells (OC-2) was tested, and the IC of CQ alone and CQ with 10μM CuCl were 9.59 and 2.22μM, respectively. The animal testing indicated that GG/GS/CQ/EDC film was decreased epidermal growth factor receptor (EGFR) expression and suppress tumor progression. These findings provide insights into a possible use for GG/GS/CQ/EDC film for oral ca in clinical practice. The GG/GS/CQ/EDC film is suitable as the dressing for use in the treatment of early-stage cancer or as wound care after surgery in late-stage of oral cancer treatment.

摘要

为了给患者提供使用更便捷的癌症药物,并提高用于口腔癌治疗的癌症药物的生物利用度,本研究制备了结冷胶/葡萄糖胺/氯碘羟喹(GG/GS/CQ)薄膜作为口腔癌治疗贴片。通过EDC介导的偶联反应制备GG/GS/CQ薄膜(GG/GS/CQ/EDC薄膜)。研究了该薄膜的物理化学性质和药物释放动力学。用动物模型评估了GG/GS/CQ/EDC薄膜作为口腔癌治疗贴片的有效性。结果证实,CQ可通过EDC介导的共价偶联结合到结冷胶/葡萄糖胺上。力学测试表明,GG/GS/CQ/EDC薄膜的最大拉伸强度和断裂伸长率分别为1.91kgf/mm和5.01%。经过45天的药物释放实验后,86.8%的CQ从GG/GS/CQ/EDC薄膜中释放出来。Huguchi模型与GG/GS/CQ/EDC药物释放数据拟合度高,相关系数分别为R = 0.9994。测试了CQ剂量对口腔癌细胞(OC-2)的影响,单独使用CQ和与10μM CuCl联合使用时CQ的半数抑制浓度分别为9.59和2.22μM。动物试验表明,GG/GS/CQ/EDC薄膜可降低表皮生长因子受体(EGFR)表达并抑制肿瘤进展。这些发现为GG/GS/CQ/EDC薄膜在口腔癌临床实践中的可能应用提供了见解。GG/GS/CQ/EDC薄膜适合用作早期癌症治疗的敷料或口腔癌晚期手术后伤口护理的敷料。

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