Assessment of PEG on polymeric particles surface, a key step in drug carrier translation.
Injectable drug nanocarriers have greatly benefited in their clinical development from the addition of a superficial hydrophilic corona to improve their cargo pharmacokinetics. The most studied and used polymer for this purpose is poly(ethylene glycol), PEG. However, in spite of its wide use for over two decades now, there is no general consensus on the optimum PEG chain coverage-density and size required to escape from the mononuclear phagocyte system and to extend the circulation time. Moreover, cellular uptake and active targeting may have conflicting requirements in terms of surface properties of the nanocarriers which complicate even more the optimization process. These persistent issues can be largely attributed to the lack of straightforward characterization techniques to assess the coverage-density, the conformation or the thickness of a PEG layer grafted or adsorbed on a particulate drug carrier and is certainly one of the main reasons why so few clinical applications involving PEG coated particle-based drug delivery systems are under clinical trial so far. The objective of this review is to provide the reader with a brief description of the most relevant techniques used to assess qualitatively or quantitatively PEG chain coverage-density, conformation and layer thickness on polymeric nanoparticles. Emphasis has been made on polymeric particle (solid core) either made of copolymers containing PEG chains or modified after particle formation. Advantages and limitations of each technique are presented as well as methods to calculate PEG coverage-density and to investigate PEG chains conformation on the NP surface.
Laboratoire de Nanotechnologie Pharmaceutique, Faculté de Pharmacie, Université de Montréal, C.P. 6128, Succursale Centre-ville, Montréal, Québec H3C 3J7, Canada; Canada Research Chair in Bio-Inspired Materials, Faculté de Pharmacie, Université de Montréal, C.P. 6128, Succursale Centre-ville, Montréal, Québec H3C 3J7, Canada.
Jean-Michel
JM
Rabanel
Laboratoire de Nanotechnologie Pharmaceutique, Faculté de Pharmacie, Université de Montréal, C.P. 6128, Succursale Centre-ville, Montréal, Québec H3C 3J7, Canada.
Patrice
P
Hildgen
Canada Research Chair in Bio-Inspired Materials, Faculté de Pharmacie, Université de Montréal, C.P. 6128, Succursale Centre-ville, Montréal, Québec H3C 3J7, Canada. Electronic address: xavier.banquy@umontreal.ca.
Xavier
X
Banquy
D004337:Drug Carriers / Q000737:chemistry*; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D053758:Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D056951:Photoelectron Spectroscopy; D011092:Polyethylene Glycols / Q000737:chemistry*; D013499:Surface Properties
D004337:Drug Carriers; D011092:Polyethylene Glycols
Coverage-density; NMR; Nanoparticle; Poly(ethylene glycol); Surface analysis; XPS