Polydisperse PEGs are ubiquitously used in pharmaceutical industry and biomedical research. However, the monodispersity in PEGs may play a role in the development of safe and effective PEGylated small molecular drugs. Here, to avoid the polydispersity in polidocanol, the active ingredient in a clinically used drug, a macrocyclic sulfate-based strategy for the efficient and scalable synthesis of monodisperse polidocanols, their sulfates, and their methylated derivatives, was developed. TLC and HPLC analysis indicated a complex mixture in regular polidocanol and high purities in monodisperse polidocanols and their derivatives. Assay on HUVEC, L929, and HePG2 cells showed that monodisperse polidocanols have much higher cytotoxicity and safety than that of regular polidocanol. It was found that the monodispersity of PEGs in polidocanols is crucial for achieving the optimal therapeutic results. Therefore, based on this case study, it would be beneficial to optimize PEGylated small molecular drugs with monodisperse PEGs in pharmaceutical research and development.

中文翻译：

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单分散聚乙二醇在药物中的应用：单分散聚二十二烷醇

多分散的PEG普遍用于制药工业和生物医学研究。但是，PEG中的单分散性可能在安全有效的PEG化小分子药物的开发中发挥作用。在这里，为了避免在多士多醇中的多分散性，开发了一种临床上使用的药物中的活性成分，开发了一种基于大环硫酸盐的策略，可以有效，可扩展地合成单分散的多士多醇，它们的硫酸盐和它们的甲基化衍生物。TLC和HPLC分析表明，在常规的多士多醇中有复杂的混合物，在单分散的多士多醇及其衍生物中具有高纯度。对HUVEC，L929和HePG2细胞的分析表明，单分散的多士多醇比常规的多士多醇具有更高的细胞毒性和安全性。发现聚乙二醇在多多酚中的单分散性对于获得最佳治疗效果至关重要。因此，基于此案例研究，在药物研究和开发中优化具有单分散PEG的PEG化小分子药物将是有益的。