PEGylation of Nanocarrier Drug Delivery Systems: State of the Art

"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.