Toxicity and immunogenicity concerns related to PEGylated-micelle carrier systems: a review

ABSTRACT Polymeric-micelle carrier systems have emerged as a novel drug-carrier system and have been actively studied for anticancer drug targeting. In contrast, toxicological and immunological concerns related to not only polymeric-micelle carrier systems, but also other nanocarrier systems, have received little attention owing to researchers’ focus on therapeutic effects. However, in recent clinical contexts, biopharmaceuticals’ effects on immune responses have come to light, requiring that researchers substantively explore the potential negative side effects of nanocarrier systems and of therapeutic proteins in order to develop nanocarrier systems suitable for clinical use. The present review describes current insights into both toxicological and immunological issues regarding polymeric-micelle carrier systems. The review focuses on immunogenicity issues of polymeric-micelle carrier systems possessing poly(ethylene glycol) (PEG). We conclude that PEG-related immunogenicity is deeply related to characteristics of a counterpart block of PEG-conjugates, and we propose future directions for addressing this unresolved issue. Graphical abstrac