Polyethylene glycol-related histopathological changes and evaluation considerations in nonclinical studies of polyethylene glycol-modified drugs
Polyethylene glycol(PEG)is a biocompatible,non-sterically hindered polymer with amphiphilic properties that is widely used to modify various types of drugs.PEGylation of drugs can decrease their clearance rate and/or alter their distribution characteristics in vivo,thereby promoting stability,prolonging their duration of action in the body,reducing the dosing frequency to maintain the treatment levels,and reducing antigenicity,and so on.Therefore,PEGylation is widely used in various drug formulations.In nonclinical histopathological studies of such drugs,PEG-associated vacuolation is frequently observed.However,the understanding of the mechanism and long-term safety of PEGylated drugs causing vacuolation is currently insufficient.Therefore,this article summarized the mechanism and influencing factors of common histopathological changes associated with PEGylated drugs,compiled existing diagnostic criteria and considerations for evaluating such histopathological changes in practice,and raised concerns from the perspective of PEGylated drugs evaluation.The goal of this article is to provide a reference for nonclinical and clinical safety assessments of PEGylated drugs.
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