Lau YongKhee, Lim Vuanghao
Integrative Medicine Cluster, Advanced Medical and Dental Institute, Universiti Sains Malaysia, Bertam, 13200 Kepala Batas, Penang Malaysia.
Chem Cent J. 2016 Nov 29;10:77. doi: 10.1186/s13065-016-0226-4. eCollection 2016.
Drug delivery directly to the colon is a very useful approach for treating localised colonic diseases such as inflammatory bowel disease, ulcerative colitis, and Crohn's disease. The use of disulphide cross-linked polymers in colon targeted drug delivery systems has received much attention because these polymers are redox sensitive, and the disulphide bonds are only cleaved by the low redox potential environment in the colon. The goal of this study was to synthesise tricarballylic acid-based trithiol monomers for polymerisation into branch-chained disulphide polymers. The monomer was synthesised via the amide coupling reaction between tricarballylic acid and (triphenylmethyl) thioethylamine using two synthesis steps. The disulphide cross-linked polymers which were synthesised using the air oxidation method were completely reduced after 1 h of reduction with different thiol concentrations detected for the different disulphide polymers. In simulated gastric and intestinal conditions, all polymers had low thiol concentrations compared to the thiol concentrations in the simulated colon condition with present. Degradation was more pronounced in polymers with loose polymeric networks, as biodegradability relies on the swelling ability of polymers in an aqueous environment. Polymer P15 which has the loosest polymeric networks showed highest degradation.
将药物直接递送至结肠是治疗局部结肠疾病（如炎症性肠病、溃疡性结肠炎和克罗恩病）的一种非常有用的方法。在结肠靶向给药系统中使用二硫键交联聚合物受到了广泛关注，因为这些聚合物对氧化还原敏感，并且二硫键仅在结肠的低氧化还原电位环境中被裂解。本研究的目的是合成基于柠檬酸的三硫醇单体，以聚合成支链二硫键聚合物。该单体通过柠檬酸与（三苯甲基）硫代乙胺之间的酰胺偶联反应，分两步合成。使用空气氧化法合成的二硫键交联聚合物，在用不同硫醇浓度还原1小时后完全还原，不同的二硫键聚合物检测到不同的硫醇浓度。在模拟胃和肠道条件下，与存在模拟结肠条件下的硫醇浓度相比，所有聚合物的硫醇浓度都较低。在聚合物网络疏松的聚合物中降解更为明显，因为生物降解性依赖于聚合物在水性环境中的溶胀能力。聚合物网络最疏松的聚合物P15表现出最高的降解率。
