PEGylation as a strategy for improving nanoparticle-based drug and gene delivery

Abstract

Coating the surface of nanoparticles with polyethylene glycol (PEG), or “PEGylation”, is a commonly used approach for improving the efficiency of drug and gene delivery to target cells and tissues. Building from the success of PEGylating proteins to improve systemic circulation time and decrease immunogenicity, the impact of PEG coatings on the fate of systemically administered nanoparticle formulations has, and continues to be, widely studied. PEG coatings on nanoparticles shield the surface from aggregation, opsonization, and phagocytosis, prolonging systemic circulation time. Here, we briefly describe the history of the development of PEGylated nanoparticle formulations for systemic administration, including how factors such as PEG molecular weight, PEG surface density, nanoparticle core properties, and repeated administration impact circulation time. A less frequently discussed topic, we then describe how PEG coatings on nanoparticles have also been utilized for overcoming various biological barriers to efficient drug and gene delivery associated with other modes of administration, ranging from gastrointestinal to ocular. Finally, we describe both methods for PEGylating nanoparticles and methods for characterizing PEG surface density, a key factor in the effectiveness of the PEG surface coating for improving drug and gene delivery.

A Model for the Transient Subdiffusive Behavior of Particles in Mucus

“…To overcome this biological barrier caused by some novel inhalation pharmaceuticals, functionalized and nontoxic nanocarriers can be used. Inspired from viruses, nanosized particles with neutrally charged coatings such as polyethylene glycol (PEG) can efficiently penetrate the mucus layer in contrast to charged particles (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12).…”

Functionalizing PLGA and PLGA Derivatives for Drug Delivery and Tissue Regeneration Applications

“…On the other hand, it has also been reported that PLGA/PEG nanoparticles can penetrate and diffuse through mucus-based layers due to the PEG properties, improving the drug delivery in the gastrointestinal or cervicovaginal tract, among others. [123] Cu and co-workers demonstrated an improvement in drug diffusion when PLGA/PEG nanoparticles penetrated the human cervical mucus into the vaginal tissue. [124] Indeed, Justin Hanes' research group proved that high densities of PEG in the surface of PLGA nanoparticles imply less interactions between mucins and nanoparticles, hence leading to a mucopenetrating profile of the nanosystem and facilitating its transport in human cervicovaginal mucus.…”

Bridging the Knowledge of Different Worlds to Understand the Big Picture of Cancer Nanomedicines

“…PEGylation has been widely used for the surface coating of the nanoparticles in order to introduce a stealth property to the nanoparticles, because PEG chains hinder the non-specific interaction of the nanoparticle's surface with the blood components due to tight hydrated layer and reduce MPS recognition, resulting in reduced uptake and clearance from the bloodstream. [39] PEGylation of liposomes have shown to extended the blood circulation time from less than 30 min to 5 h after systemically administration, conferring the 'stealth effect' of PEGylation. [40] Similarly, PEGylated poly(lacticco-glycolic acid) (PLGA) nanoparticles have shown to significantly increased the blood circulation half-life together with reduced liver uptake, compared to non-PEGylated PLGA nanoparticles.…”