Achievements and Bottlenecks of PEGylation in Nano-delivery Systems

Abstract

Poly(ethylene glycol) (PEG) has been widely applied in biomedical field as a gold standard. The conjugation of PEG to proteins, peptides, oligonucleotides (DNA, small interfering RNA (siRNA), microRNA (miRNA)) and nanoparticles, also known as PEGylation, is a common method to improve the efficiency of drug delivery and pharmacokinetics in vivo. The effect of PEGylation on the in vivo fate of various formulations has been and continues to be extensively studied based on the successful PEGylation of proteins to improve in vivo circulation time and reduce immunogenicity. The PEG shell protects the particles from aggregation, immune recognition, and phagocytosis, thereby prolonging the in vivo circulation time. This article mainly describes the development background, advantages and applications of PEGylation in the field of drug delivery, its defects or development bottlenecks, and possible alternatives.

Evasion of opsonization of macromolecules using novel surface‐modification and biological‐camouflage‐mediated techniques for next‐generation drug delivery

“…55 In water, the PEG-chains undergo spontaneous motion leading to volume displacement and subsequent generation of steric forces in turn preventing opsonization of nanoparticles. 56 In addition, the PEG-chains also block hydrophobic and electrostatic interactions restricting the ability of micromolecular-opsonins to form hard corona with the nanoparticles like polystyrene, and so forth. 57 T A B L E 1 Various surface-modification methods to prevent opsonization.…”

“…PEG imparts stealth properties to nanoparticles by formation of an intermittent barrier layer between nanoparticulate surface and the external environment 55 . In water, the PEG‐chains undergo spontaneous motion leading to volume displacement and subsequent generation of steric forces in turn preventing opsonization of nanoparticles 56 . In addition, the PEG‐chains also block hydrophobic and electrostatic interactions restricting the ability of micromolecular‐opsonins to form hard corona with the nanoparticles like polystyrene, and so forth 57 .…”

Study of uricase-polynorbornene conjugates derived from grafting-from ring-opening metathesis polymerization

“…10 However, growing instances show clinical evidence of adverse effects attributed mainly to pre-existing anti-PEG antibodies recognizing either the polymer backbone or the methoxy end group of the polymer. 11,12 Studies indicate that up to 72% of humans who have not been treated with PEGylated therapies still have pre-existing anti-PEG antibodies. [13][14][15][16][17][18][19][20][21][22][23][24] These elevated occurrences are believed to result from extensive exposure to PEG and PEG derived substances through common everyday products.…”