Date of Award

8-2009

Level of Access Assigned by Author

Campus-Only Dissertation

Degree Name

Doctor of Philosophy (Medical Science)

Department

Chemistry

Advisor

Carl P. Tripp

Second Committee Member

Raymond C. Fort, Jr.

Third Committee Member

Touradj Solouki

Abstract

Liposomes are self-assembled structures that contain an inner aqueous compartment surrounded by a lipid bilayer typically composed of phospholipids and sterols. Liposomes are widely used as model systems for cell membrane and as drug carriers in drug delivery systems. While there are numerous studies that focus on the functionality aspects of liposomes membrane, there are comparatively few studies that provide experimental data on the molecular interactions giving rise to the functionality. Thus, obtaining molecular details of a liposome membrane and its relationship to properties and functions of liposomes such as membrane permeability, and stability to surfactants, temperature, pH and ionic strength is lacking and much needed. The objective of the work in this thesis is to obtain molecular information on liposome membranes and is directed by the development of infrared (IR) based methods. Specifically, these IR based methods are used to probe molecular details of liposome structure and the interactions with surfactants and sterols. The approach uses attenuated total reflection - Fourier transform infrared spectroscopy (ATR-FTIR) in which ZnSe internal reflection elements (IRE) are coated with a high surface area TiO2. A TiO2 coating is used because the liposomes readily adsorb and remain intact on TiO2. Moreover, the liposomes remain anchored to the TiO2 for days while flowing water at rates of 1 ml/min. By using ATR-FTIR, it is possible to record spectra in situ and to extract molecular detail on composition of liposomes. Furthermore, the use of ATR-FTIR allows for recording spectra as a function of time and as a result enables the use of IR spectra to detect dynamic processes occurring during the initial adsorption of the liposomes and during subsequent interactions with other molecules. As is demonstrated in this thesis, it is possible to establish the fundamental relationship between changes in the IR spectrum with the conformational changes of the liposomes.

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