More and more therapeutic proteins are developed for an administration by inhalation to treat respiratory diseases. PEGylation is an interesting approach for sustaining the residence time of these biopharmaceuticals in the lungs and thereby decrease the frequency of administration and the daily burden of inhalation therapies. Several PEGylated proteins have been delivered to the lungs in rodents and shown to be retained in the respiratory tract for longer periods than unconjugated counterparts. Mechanisms involved in their pulmonary retention might include increased molecular size, mucoadhesion, enhanced proteolytic resistance and escape from the uptake by alveolar macrophages. Pulmonary delivery of PEGylated peptides and proteins is also interesting as a non-invasive route of administration of long-acting biopharmaceuticals to the bloodstream. However, PEGylation decreases the systemic absorption of the compounds, especially when the PEG size is large. This review presents the recent work carried out on the pulmonary delivery of PEGylated biopharmaceuticals, the factors affecting residence time in the lungs and systemic absorption as well as the safety of the approach in preclinical studies.

越来越多的治疗性蛋白质被开发用于通过吸入给药来治疗呼吸系统疾病。聚乙二醇化是维持这些生物药物在肺中的停留时间，从而减少给药频率和吸入疗法每日负担的有趣方法。几种聚乙二醇化蛋白已在啮齿动物中被递送到肺部，并显示出它们在呼吸道中的保留时间比未结合的对应物更长。参与其肺部保留的机制可能包括分子大小增加，粘膜粘附，增强的蛋白水解抗性和逃避肺泡巨噬细胞的摄取。聚乙二醇化肽和蛋白质的肺部递送作为将长效生物药物施用到血液中的非侵入性途径也是令人感兴趣的。但是，聚乙二醇化会降低化合物的全身吸收，特别是当聚乙二醇较大时。这篇综述介绍了关于在肺部输送聚乙二醇化生物药物的最新工作，影响在肺中停留时间和全身吸收的因素以及该方法在临床前研究中的安全性。