This dissertation explores the potential of using perfluorocarbon emulsion droplets to add an ultrasound-sensitive element to drug delivery systems. These emulsion droplets may be induced to vaporize with ultrasound; during the rarefactional phase of an ultrasound wave, the pressure around the droplets may fall below the vapor pressure of the liquid forming the emulsion, providing a thermodynamic potential for vaporization. This ultrasound-induced phase change of the emulsion droplet could release therapeutics attached to the droplet surface or aid in drug delivery due to mechanical effects associated with vaporization and expansion, similar to the ability of cavitating bubbles to aid in drug delivery. In contrast to bubbles, stable emulsions can be formed at nano-scale sizes, allowing them to extravasate into tissues and potentially be endocytosed into cells. Perfluorohexane and perfluoropentane were selected to form the emulsions due to their relatively high vapor pressure, low water solubility, and biocompatibility. Acoustic droplet vaporization was explored for its potential to increase ultrasound-induced drug release from liposomes. Liposomes have proven to be versatile and effective drug carriers, but are not inherently responsive to ultrasound. eLiposomes, defined as a liposome with encapsulated emulsion droplets, were developed due to the potential of the expanding vapor phase to disrupt bilayer membranes. The resulting vesicle retains the advantages of liposomes for drug delivery, while adding an ultrasound-sensitive element. eLiposomes were loaded with calcein, a fluorescent molecule, as a model drug in order to quantify ultrasound-mediated drug release compared to release from conventional liposomes. Upon exposure to ultrasound, eLiposomes typically released 3 to 5 times as much of the encapsulated load compared to conventional liposomes, with some eLiposome samples approaching 100% release. Emulsion droplets were also added to the outside of conventional liposomes, but resulted in little to no increase compared to control samples without emulsions. Lastly, in vitro experiments were performed with HeLa cells to explore the ability of emulsion droplets and eLiposomes to deliver calcein inside of cells. Calcein delivery to the cytosol was accomplished, and the emulsion-containing samples demonstrated the ability to aid in endosomal escape.
| Identifer | oai:union.ndltd.org:BGMYU2/oai:scholarsarchive.byu.edu:etd-4376 |
| Date | 13 November 2012 |
| Creators | Lattin, James R. |
| Publisher | BYU ScholarsArchive |
| Source Sets | Brigham Young University |
| Detected Language | English |
| Type | text |
| Format | application/pdf |
| Source | Theses and Dissertations |
| Rights | http://lib.byu.edu/about/copyright/ |
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