Investigating the Hydration Environments of PEGylated Liposomes Utilizing Overhauser Dynamic Nuclear Polarization

Mingwei Zhou, Gail Fanucci

University of Florida

Liposomes are biodegradable and biocompatible lipid bilayer vesicles that are widely used carriers for delivering therapeutic agents to treat various diseases. In serum, liposomes as a drug delivery system need protection for evasion of clearance of the reticulo-endothelial system. Therefore, polyethylene glycol (PEG) moieties are introduced, coating the liposomes for a longer blood circulation time and a better drug delivery efficiency. Two conformations (mushroom- or brush-like) are found with varying PEG sizes and grafting density applied in liposome synthesizing. However, there is still a lack of comprehensive understanding of the effect of PEGylation of liposomes physiochemically properties. In recent years, with the development of spectroscopies and MD simulations, investigations of hydration shells led to a new and detailed insight into the structures and functions of biomolecules. A novel technique for studying hydration shells is Overhauser dynamic nuclear polarization (ODNP) measurements, which could estimate the translational dynamics of water molecules within approximately 10 Å from one spin-label. In this study, by applying spin-labels (SL) to four different locations of liposomes, we will introduce ODNP techniques to investigate how hydration environments change with liposomes PEGylated with different mole fractions of PEG systemically. Further studies of the hydration environment changes of PEGylated pH-sensitive liposomes with pH varying will also be conducted.