Poly(ethylene glycol) or PEG has a long history of use in medicine. Many conventional formulations utilize PEG as either an active ingredient or an excipient. PEG found its use in biotechnology therapeutics as a tool to slow down drug clearance and shield protein therapeutics from undesirable immunogenicity. Nanotechnology field applies PEG to create stealth drug carriers with prolonged circulation time and decreased recognition and clearance by the mononuclear phagocytic cells (MPS). Most nanomedicines approved for clinical use and experimental nanotherapeutics contain PEG. Among the most recent successful examples are two mRNA-based COVID-19 vaccines that are delivered by PEGylated lipid nanoparticles. The breadth of PEG use in a wide variety of over the counter (OTC) medications as well as in drug products and vaccines stimulated research which uncovered that PEG is not as immunologically inert as it was initially expected. Herein, we review the current understanding of PEG’s immunological properties and discuss them in the context of synthesis, biodistribution, safety, efficacy, and characterization of PEGylated nanomedicines. We also review the current knowledge about immunological compatibility of other polymers that are being actively investigated as PEG alternatives.

聚乙二醇或 PEG 在医学上的应用有着悠久的历史。许多传统制剂利用 PEG 作为活性成分或赋形剂。 PEG 在生物技术治疗中被用作减缓药物清除和保护蛋白质治疗免受不良免疫原性影响的工具。纳米技术领域应用PEG来制造隐形药物载体，延长循环时间并减少单核吞噬细胞（MPS）的识别和清除。大多数批准用于临床的纳米药物和实验性纳米疗法都含有 PEG。最近的成功例子是两种基于 mRNA 的 COVID-19 疫苗，它们通过聚乙二醇化脂质纳米粒子传递。 PEG 在各种非处方 (OTC) 药物以及药品和疫苗中的广泛应用激发了研究，发现 PEG 并不像最初预期的那样具有免疫惰性。在此，我们回顾了目前对 PEG 免疫学特性的理解，并在聚乙二醇化纳米药物的合成、生物分布、安全性、功效和表征的背景下进行了讨论。我们还回顾了有关其他聚合物免疫相容性的最新知识，这些聚合物正在作为 PEG 替代品进行积极研究。