Despite its advantages, PEGylation may present some challenges. The "PEG dilemma" refers to the paradox where, although PEGylation reduces immunogenicity, repeated administration of PEGylated compounds can lead to the formation of anti-PEG antibodies. These antibodies can accelerate the clearance of PEGylated drugs from the body, reducing their efficacy. Therefore, ongoing research focuses on developing alternative polymers or modifying PEG structures to overcome these challenges.
