Lin F H, Lee Y H, Jian C H, Wong Jau-Min, Shieh Ming-Jium, Wang Cheng-Yi
College of Medicine, Institute of Biomedical Engineering, National Taiwan University, Taipei.
Biomaterials. 2002 May;23(9):1981-7. doi: 10.1016/s0142-9612(01)00325-8.
Since its introduction over 40 years ago, 5-fluorouracil (5-FU) has remained the only effective chemotherapy option available for the treatment of colorectal cancer (CRC). However, this cytotoxic anticancer drug often causes severe side effects because it does not act selectively on the tumor. It has been reported that the 5-FU showed considerable toxicity when administered by intravenous injections or via alimentary tract. Although, many materials have been developed for carrying 5-FU, there has been no clinically acceptable carrier for 5-FU till now. Montmorillonite, one of the clay minerals, consists of hydrated aluminum silicates with fine grains and large spaces between the layers. Isomorphous substitution of cations is common. In the study, we attempt to intercalate 5-FU into interlayers of montmorillonite through ion exchange. Montmorillonite was purified from crude clays of bentonite in Tai-dong, Taiwan by filtration and sedimentation. Solutions of 5-FU with different concentrations were prepared by dissolving various amounts of 5-FU into 10 ml NaOH solution. Purified montmorillonite powder was soaked in 5-FU solution for a period of time with different pH values and temperatures. In this study, we try to intercalate 5-FU into interlayers of montmorillonite to find out optimum conditions, such as soaking time, temperature, pH value, initial 5-FU concentration, etc., to prepare composites of 5-FU and montmorillonite (5-FU/mont). UV, SDT, FTIR, XRD are used to characterize the 5-FU/mont composite. From the results. 5-FU was successfully intercalated into the interlayer of montmorillonite both by free surface absorption and OH replacement. The optimum condition for 5-FU/mont preparations is 1.185 wt% of 5-FU as initial concentration under a pH value of 11.6 at a temperature of 80 degrees C and a soaking time of 2 h. The total amount of 5-FU in montmorillonite is about 87.5 mg for each gram of montmorillonite, which can be proved by thermal gravimetric analysis. The composite of 5-FU/mont is expected to achieve in situ release for colorectal cancer therapy in future applications.
自40多年前问世以来，5-氟尿嘧啶（5-FU）一直是治疗结直肠癌（CRC）唯一有效的化疗药物。然而，这种细胞毒性抗癌药物常引发严重副作用，因为它并非选择性地作用于肿瘤。据报道，静脉注射或经消化道给药时，5-氟尿嘧啶显示出相当大的毒性。尽管已经研发出多种用于负载5-氟尿嘧啶的材料，但迄今为止，尚无临床上可接受的5-氟尿嘧啶载体。蒙脱石是一种粘土矿物，由具有细颗粒和层间大空隙的水合铝硅酸盐组成。阳离子的同晶取代很常见。在本研究中，我们试图通过离子交换将5-氟尿嘧啶插入蒙脱石的层间。通过过滤和沉淀从台湾台东膨润土的粗粘土中提纯蒙脱石。将不同量的5-氟尿嘧啶溶解在10毫升氢氧化钠溶液中，制备不同浓度的5-氟尿嘧啶溶液。将提纯的蒙脱石粉末在不同pH值和温度下浸泡在5-氟尿嘧啶溶液中一段时间。在本研究中，我们试图将5-氟尿嘧啶插入蒙脱石层间，以找出制备5-氟尿嘧啶与蒙脱石复合材料（5-FU/mont）的最佳条件，如浸泡时间、温度、pH值、初始5-氟尿嘧啶浓度等。使用紫外光谱（UV）、同步热分析（SDT）、傅里叶变换红外光谱（FTIR）、X射线衍射（XRD）对5-FU/mont复合材料进行表征。结果表明，5-氟尿嘧啶通过自由表面吸附和羟基置换成功插入蒙脱石层间。制备5-FU/mont的最佳条件是：初始浓度为1.185 wt%的5-氟尿嘧啶，pH值为11.6，温度为80℃，浸泡时间为2小时。热重分析表明，每克蒙脱石中5-氟尿嘧啶的总量约为87.5毫克。5-FU/mont复合材料有望在未来应用中实现结直肠癌治疗的原位释放。
