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Dissertation Defense: Gamid Abatchev

October 5 @ 11:00 am - 12:00 pm MDT

Dissertation Information

Title: Liposomes: Production and Applications for Controlled Drug Delivery

Program: Doctor of Philosophy in Biomolecular Sciences

Advisor: Dr. Daniel Fologea (Department of Physics)

Committee Members: Dr. Denise Wingett (Department of Biological Sciences), Dr. Julie Oxford (Department of Biological Sciences), and Dr. Juliette Tinker (Department of Biological Sciences)

Abstract

Liposomes are the most advanced nano-carriers used for numerous investigations and applications, spanning from fundamental scientific research to consumer and agricultural products, to FDA approved drug delivery vehicles. Their increasing importance, prevalence, and capabilities served as a motivation for these studies. This dissertation recognizes the enormous potential presented by the ever-evolving capacities of liposomes as drug carriers and seeks to offer further investigation into their production and utilization. After briefly introducing the basic principles governing their formation by self-assembly in water solutions, the most common production methods are described, and key advances that led to their use as drug carriers are pointed out. Next, production of liposomes by the traditional methods of extrusion and sonication, detailing passive and active loading, as well as physical characterization by Dynamic Light Scattering, microscopy imaging, and fluorescence spectroscopy, are demonstrated. Furthermore, a novel approach developed by our lab for liposome preparation that relies on removal of lipid-solubilizing agents and charged dyes from solutions by electrodialysis, is described. This methodology allows accelerated preparation of loaded and purified liposomes, resembling characteristics of ones prepared by traditional methods, in only a few steps. Finally, concluding investigations illustrate achieving controlled release of liposomal cargo, which is a major roadblock for many current clinical applications. This is realized with liposomes designed to respond to either radiation or internal pH changes resulting from irradiation of organic halogen solutions. The pairing of X-ray irradiation as a stimulus for releasing chemotherapeutic loaded cargo from liposomes offers possibility for truly concomitant application of radio and chemotherapy, potentially resulting in supra-additive efficacy of treating tumors.