The viscoelastic mucus secretions coating exposed organs such as the lung airways and the female reproductive tract can trap and quickly eliminate not only foreign pathogens and ultrafine particles but also particle-based drug delivery systems, thus limiting sustained and targeted drug delivery at mucosal surfaces. To improve particle distribution across the mucosa and enhance delivery to the underlying epithelium, many investigators have sought to develop nanoparticles capable of readily traversing mucus. The first synthetic nanoparticles shown capable of rapidly penetrating physiological mucus secretions utilized a dense coating of polyethylene glycol (PEG) covalently grafted onto the surface of preformed polymeric nanoparticles. In the decade since, PEG has become the gold standard in engineering mucus-penetrating drug carriers for sustained and targeted drug delivery to the lungs, gastrointestinal tract, eyes, and female reproductive tract. This review summarizes the history of the development of various PEG-based mucus-penetrating particles, and highlights the key physicochemical properties of PEG coatings and PEGylation strategies to achieve muco-inert PEG coatings on nanoparticle drug carriers for improved drug and gene delivery at mucosal surfaces.

粘弹性粘液分泌物覆盖暴露的器官，例如肺气道和女性生殖道，不仅可以捕获并快速消除外来病原体和超细颗粒，而且可以捕获并快速消除基于颗粒的药物输送系统，从而限制了在粘膜表面持续和有针对性的药物输送。为了改善整个粘膜上的颗粒分布并增强向下层上皮的递送，许多研究者已经寻求开发能够容易地穿过粘液的纳米颗粒。显示出能够快速穿透生理粘液分泌的第一批合成纳米颗粒利用了共价接枝到预成型的聚合物纳米颗粒表面的聚乙二醇（PEG）的致密涂层。从那以后的十年中 PEG已成为工程性渗透粘液的药物载体的金标准，用于将药物持续，有针对性地输送到肺部，胃肠道，眼睛和女性生殖道。这篇综述总结了各种基于PEG的粘液穿透颗粒的发展历史，并重点介绍了PEG涂层的关键物理化学性质和PEG化策略，以在纳米颗粒药物载体上实现对粘液惰性的PEG涂层，从而改善了在粘膜表面的药物和基因的递送。 。