CATANIONIC SURFACTANT VESICLES: TECHNOLOGY FOR VACCINE DEVELOPMENT AND TARGETED DRUG DELIVERY APPLICATIONS

Abstract

Catanionic surfactant vesicles have gained attention due to their structural similarities to liposomes and their robust properties in biological media. Catanionic vesicles are formed from oppositely charged surfactants and can be exploited for applications in vaccine production and drug delivery. The focus of my research has been on the preparation, characterization, and application of functionalized catanionic surfactant vesicles. Chapter 2 describes the preparation and characterization of catanionic vesicles containing sodium dodecylbenzenesulfonate (SDBS) and cetyltrimethylammonium tosylate (CTAT). Vesicle solutions were determined to be stable for greater than 6 months, formed vesicles with two populations of 80 and 160 nm, and had a membrane surface charge similar to human cells, -56 mV. Furthermore, vesicles were stable between a pH of 2 and 12, in saline solutions up to 0.6 M NaCl, and after autoclaving. Next, I report the loading of various molecules into the vesicle leaflet and the characterization of the resulting functionalized systems. Hydrophobic molecules were readily incorporated into the hydrophobic region of the leaflet. Lipid conjugates of hydrophilic molecules were anchored in the vesicle bilayer. Chapters 3 and 4 report the loading of biological materials (i.e. liposaccharides and proteins) into catanionic vesicles for the development of bacterial vaccines. Initial studies, discussed in Chapter 3, pertain to the loading of the pure components lipooligosaccharide (LOS) and C12 -Pan DR helper T cell epitope (PADRE) conjugate into catanionic vesicles. A single dose of these vesicles generated a large IgG antibody titer in mice. Next, in Chapter 4, we focus on the extraction of cellular membrane components from cells for their direct incorporation into catanionic vesicles. Vesicles were prepared by adding surfactants in the presence of Neisseria gonorrhoeae cells. Vesicle extracts contained pathogen-derived LOS F62ΔlgtD and a subset of proteins from the outer membrane of the bacterium, including porin and OPA. Lastly, Chapter 5 describes catanionic vesicles in drug delivery. Vesicles were loaded with 88 μg/mL of doxorubicin and shown to retain the drug over 15 days. Doxorubicin loaded into catanionic vesicles were shown to be less toxic as compared to the free drug, IC 50 = 51 μg/mL and 0.16 μg/mL, respectively.