Investigation of the interaction between poly(ethylene glycol) and protein molecules using low field nuclear magnetic resonance.

A comprehensive insight into the interaction between proteins and poly(ethylene glycol) (PEG) is crucial to understand the behavior of PEG, which is widely used in pharmaceutical and medical applications. Although PEG is believed to be an excellent material to resist non-specific protein adsorption, there is a lack of quantitative information about the interactions between proteins and PEG. In this paper the interactions of bovine serum albumin (BSA) and lysozyme (LYZ) with different molecular weight (MW) PEGs were investigated through the T2 relaxation time of PEGs measured by low field nuclear magnetic resonance spectroscopy. The integrated signal intensity of PEGs was quantified under various conditions from the concentrations and MWs of PEG, and ionic strength of solutions, as well as the molar ratios of PEG to protein. The results show that a large number of PEG molecules could associate with protein molecules with association constants in the range ~10(4)-10(5) M(-1). The association constant is insensitive to the ionic strength change in the physiological range and the lowest associate constant occurs at the medium MW PEG with protein. This suggests that the interaction between PEG and protein molecules might not be negligible in investigations of the resistance to non-specific protein adsorption. Long chain PEG coatings might cause modest protein adsorption, which could interfere with any weak specific interaction between ligand and receptor. Thus, it is necessary to reconsider the popular accepted method of protecting nanoparticles (NP) in blood with long chain PEG coatings since these NPs might be surrounded by a layer of weakly adsorbed plasma protein in the circulatory system.