Analysis of the properties of phospholipid bilayers for drug delivery using solid-state NMR

Abstract

Phospholipid bilayers have many uses throughout science and engineering, and spherical forms of lipid bilayers called liposomes have led the field of nano drug delivery for many years. Their exact nature can be complex and dependent on a variety of different conditions, and therefore they can face more difficulties entering the clinic. For this reason, understanding how these membranes behave is of crucial importance and of great interest to researchers in academia and industry. In this thesis the aim is to demonstrate methods in which solid-state NMR can be used as a technique in conjunction with others to be able to gain further knowledge of their properties. As part of this an aptamer liposome was developed, and the impact of PEGylated lipids on the formulation were examined. This formulation was then further investigated using X-Ray scattering and solid-state NMR, to demonstrate how the PEG chains and surface aptamer interacted. This section of the thesis shows how important an understanding of how surface moieties are interacting is in drug delivery. Following this, two more general methods to understand structures are shown. 17O-NMR spectroscopy is used to understand the hydrogen bonding of cholesterol in lipid bilayers, and the potential of lanthanide NMR as a tool to investigate lipid bilayers was demonstrated on pharmaceutically relevant lipid structures. This thesis demonstrates the applicability of solid-state NMR to drug delivery liposomes using commonly used techniques and some that are less well known to enable better understanding of lipid bilayers.