PEGylation of Nanocarrier Drug Delivery Systems: State of the Art

Abstract

"PEGylation" has become the most widely used method for imparting stealth properties to drug nanocarriers. PEGylation of nanoparticles provides a steric barrier to the adsorption of opsonin proteins due to the neutrality, hydrophilicity, flexibility, and capacity for hydration of the PEG moiety. PEGylation of particle surfaces can be achieved by simple adsorption or through the covalent attachment of PEG to activated functional groups on the surface of the particles. PEG molecules have also been modified to enhance their uptake by specific targets (e.g., tumors) and to achieve the controlled release of entrapped therapeutic agents. Accompanying the prevalence of PEGylation has been the development of a wide variety of characterization techniques and the increasing use of mathematical modeling to guide formulation development. This review summarizes the theories behind PEGylation, PEGylation methodology, the characterization of PEGylated particles, and related mathematical modeling as well as how it can be utilized in the optimization of nanocarrier drug delivery systems. The current successes and failures of PEGylation are evaluated in order to provide a vision for the future of nanocarrier PEGylation and nanomedicine in general.

PEGylated Inorganic Nanoparticles

“…[35] In addition several polymers such as polysaccharides, polyacrylamide, poly(vinyl alcohol), poly(N-vinyl-2-pyrrolidone), poly(ethylene glycol) (PEG), and PEG-containing copolymers, have been used to coat the surface of NPs for additional stability, water solubility, and modification of surface charges. [34,36,37] Among all the polymers tested for improving the solubility and biocompatibility of NPs, PEG and PEG-copolymers [38,39] are currently most popular and found to be most effective in shielding the surface charge of NPs. The term PEGylation is used specifically for the attaching or coating of the NP surface with PEG molecules through surface adsorption, covalent linkages (by anchoring groups), and entrapment.…”

PEGylation of biodegradable dextran nanogels for siRNA delivery

“…Such groups can block the electrostatic and hydrophobic interactions through which opsonins bind to the surface of particles (Owens and Peppas, 2006). PEGylation, which refers to the decoration of a particle surface by the covalently grafting, entrapping, or adsorbing of polyethylene glycol (PEG) chains, is such a technique (Howard et al, 2008). Some authors claim that PEGylation does not really prevent the binding of opsonins but rather changes the opsonization pattern.…”

Block copolymer nanoassemblies

“…PEG is one of the widely used FDAapproved hydrophilic polymers to design amphiphilic block copolymers [10]. Polyesters, such as poly(lactic acid) (PLA), poly(glycolic acid) (PGA) and poly(caprolactone) (PCL) are also FDA-approved and frequently used for building up the hydrophobic segment of self-assembling block copolymers.…”