Polyethylene Glycol Modification: Relevance of Improved Methodology to Tumour Targeting

Abstract

Of all the polymers applied to molecule altering structural chemistry, polyethylene glycol (PEG) modification has numerous benefits and relatively few drawbacks. PEG is now increasingly being applied to the problems of tumour targeting, both in the context of the passive targeting of PEG-liposomes and in active targeting strategies using PEGylated anti-tumour antibodies. PEG can also serve as a useful linker molecule between targeting moieties and other agents, including cytotoxic or imaging agents and targeted liposomes. Despite these demonstrated benefits and the level of attention which PEGylation has received, relatively little consideration has been given to two key areas: first, the extent to which the coupling method has an impact on both the functionality of the PEG-adduct and the acquisition of beneficial properties; second, that the impact of PEGylation on biodistribution is complex, thus any attempt to optimise a PEG-peptide or PEG-liposome for a particular task must involve an examination of all the individual facets of the effects of PEGylation. Studies investigating the underlying principles of tumour targeting suggest that current views concerning the optimisation of PEGylated vehicles for tumour localisation need to be re-examined.

EGFR-targeted stearoyl gemcitabine nanoparticles show enhanced anti-tumor activity

“…Conjugation of the EGF or the OVA to the terminal of the PEG chains on the GemC18-NPs was likely responsible for the shorter half-life observed. It is known that the ability of the PEG to extend the blood circulation time of a drug carrier is related to parameters such as the amount and the molecular weight of the PEG [32]. Therefore, further future research efforts are underway to examine the feasibility of extending the half-life of the EGF-GemC18-NPs by increasing the amount of PEG(2000) in the formulation or using longer PEG molecules.…”

Polyester Dendritic Systems for Drug Delivery Applications: In Vitro and In Vivo Evaluation

“…In this instance, the trifunctional PEO core contributes most of the mass of the system. The advantages of using a star-PEO also include its contribution to biocompatibility and water solubility (40), without jeopardizing the polydispersity of the system, since star-PEO molecules with low polydispersity indices (PDI < 1.1) are commercially available. On the other hand, the [G-2] polyester dendrons of III provide the multivalency necessary for drug attachment.…”

Synthesis of nanogels/microgels by conventional and controlled radical crosslinking copolymerization

“…It has for instance been demonstrated that poly(ethylene glycol) (PEG) coatings prolong considerably the circulation time of polymeric nanoparticles in the blood stream. 25 Finally, the presence of such long stabilizing polymer chains at their surface may impart nano-/microgels with high stability and prevent them from aggregation.…”