The Effect of Lipid Chemistry and Structure on Liposome Formation
Lipids have been known to self-assemble into vesicles for over four decades; a process that has been exploited in fields ranging from drug delivery to the study of cellular mimics. The supramolecular properties of the liposome are primarily determined by the individual lipids which comprise it. Small changes to the architecture or chemistry of the lipid can result in significant alterations to both liposomal properties and the ease of liposome formation, and sometimes result in the formation of an entirely different aggregation phase (micelle, fiber, tube, etc...). Both experimental and theoretical methods have been employed to devise a framework for predicting how a given lipid will assemble in water and how the resulting liposomal will behave. To date, a number of basic principles exist that focus primarily on traditional phospholipids systems. My thesis work has added a number of new lipids that might be used to further test the properties of bilayer formation.
In the first chapter of this thesis, I discuss how lipid structure can affect liposomal properties relevant to drug delivery. In the second and third chapters, I report on novel lipids that explore how alterations to the charge-orientation and type of anion in the lipid headgroup affect the liposome's biophysical characteristics (i.e. transition temperature, permeability, surface potential, interaction with divalent cations) and in one case, even eliminates the lipid's ability to form vesicles under standard conditions. In the fourth and fifth chapters of this thesis, I describe a class of synthetic zwitterionic bolaamphiphiles that is capable of forming small diameter vesicles and discuss the possible configurations of the compounds within the vesicle wall as well as modifications to the bolaamphiphile that may enable them to be used in drug delivery. Each of these four classes of new lipids produced vesicles with unpredicted and interesting properties. They should provide biophysical chemists additional tools to study the physical and chemical properties of membranes and could contribute to the development of new liposome therapeutics.