Ng Yoke Mooi, Mat Yusuf Siti Nur Aishah, Chiu Hock Ing, Lim Vuanghao
Integrative Medicine Cluster, Advanced Medical and Dental Institute, Universiti Sains Malaysia, Bertam, Kepala Batas 13200, Penang, Malaysia.
Department of Chemical Engineering Technology, Faculty of Engineering Technology, Universiti Malaysia Perlis, UniCITI Alam Campus, Padang Besar 02100, Perlis, Malaysia.
Pharmaceutics. 2020 May 18;12(5):461. doi: 10.3390/pharmaceutics12050461.
Cystamine-based polymers may help to achieve controlled and targeted drug delivery to the colon due to their susceptibility to breakage of the disulfide linkage in the low redox potential environment of the colon. In this study, two linear cystamine-based polymers with similar repeating units (LP1 and LP2) and a cross-linked cystamine-based polymer (BP) were synthesised and their kinetics and the various physical conditions underlying cystamine-based polymerisation were evaluated. In brief, , -bis(2-(tritylthio)ethyl)adipamide () was synthesised from the reaction of triphenylmethanol and cysteamine. Next, the trityl group of was removed with trifluoroacetic acid and triethylsilane before proceeding to oxidative polymerisation of the end product, , -bis(2-mercaptoethyl)adipamide () to LP1. The Schotten-Bauman reaction was applied to synthesise LP2 and BP from the reaction of cystamine with adipoyl chloride or trimesoyl chloride. Scanning electron microscopy, energy-dispersive X-ray spectroscopy, and mapping showed that oxygen, nitrogen, sulfur, and carbon were homogenously distributed in the polymers, with LP2 and BP having less porous morphologies compared to LP1. Results of zinc-acetic acid reduction showed that all polymers began to reduce after 15 min. Moreover, all synthesised polymers resisted stomach and small intestine conditions and only degraded in the presence of bacteria in the colon environment. Thus, these polymers have great potential for drug delivery applications. LP2 and BP, which were synthesised using the Schotten-Bauman reaction, were more promising than LP1 for colon-targeted drug delivery.
基于胱胺的聚合物可能有助于实现对结肠的可控靶向药物递送，因为它们在结肠的低氧化还原电位环境中易受二硫键断裂的影响。在本研究中，合成了两种具有相似重复单元的线性基于胱胺的聚合物（LP1和LP2）以及一种交联的基于胱胺的聚合物（BP），并评估了它们的动力学以及基于胱胺聚合的各种物理条件。简而言之，通过三苯甲醇与半胱胺的反应合成了双（2 - （三苯甲基硫代）乙基）己二酰胺（ ）。接下来，在用三氟乙酸和三乙基硅烷除去 的三苯甲基基团后，再将最终产物双（2 - 巯基乙基）己二酰胺（ ）氧化聚合成LP1。应用肖滕 - 鲍曼反应，通过胱胺与己二酰氯或均苯三甲酰氯的反应合成LP2和BP。扫描电子显微镜、能量色散X射线光谱和映射显示，氧、氮、硫和碳在聚合物中均匀分布，与LP1相比，LP2和BP具有较少的多孔形态。锌 - 乙酸还原结果表明，所有聚合物在15分钟后开始还原。此外，所有合成的聚合物都能抵抗胃和小肠环境，并且仅在结肠环境中的细菌存在下才会降解。因此，这些聚合物在药物递送应用中具有巨大潜力。使用肖滕 - 鲍曼反应合成的LP2和BP在结肠靶向药物递送方面比LP1更有前景。
