Publication Date

12-2021

Date of Final Oral Examination (Defense)

10-5-2021

Type of Culminating Activity

Dissertation

Degree Title

Doctor of Philosophy in Biomolecular Sciences

Department

Biology

Supervisory Committee Chair

Daniel Fologea, Ph.D.

Supervisory Committee Member

Julia Thom Oxford, Ph.D.

Supervisory Committee Member

Juliette Tinker, Ph.D.

Abstract

This dissertation recognizes the enormous potential presented by the ever-evolving development of liposomes as drug carriers and seeks to offer further investigation into their useful production and utilization. The first chapter presents the basic principles governing their formation by self-assembly in water solutions, briefly describes the most common production methods, and points out essential past advances that led to their use as drug carriers. Chapter two exemplifies 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. In the next chapter, a novel approach for liposome preparation that relies on removing a lipid-solubilizing detergent from lipid mixtures by electrodialysis is introduced and compared to traditional preparation techniques. This methodology allows accelerated preparation of loaded and purified liposomes, resembling characteristics of ones prepared by traditional methods, in only a few steps. The final experimental chapter is focused on achieving controlled release of liposomal cargo, which is a major roadblock for many current clinical applications. This is realized by irradiation of liposomes containing PhotoClick lipids, as well as pH sensitive liposomes activated by 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.

DOI

https://doi.org/10.18122/td/1888/boisestate

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