Date on Master's Thesis/Doctoral Dissertation
University of Louisville
JB Speed School of Engineering
Targeted Double Emulsions; Ultrasound-Responsive; Molecular Therapeutics; Microfluidics
Cancer is the second leading cause of death in the United States, with 1.74 million new cancer cases diagnosed and 610,000 cancer deaths expected in 2018 alone. Current treatments often result in negative systemic effects and ineffective treatment of the tumor. Drug delivery vehicles have been developed for more effective local delivery methods, but many drug delivery vehicles lack spatial and temporal control. Targeted double emulsions are a new class of drug delivery vehicles which present a promising option for a high payload and controlled delivery. The purpose of our project was to develop and characterize an aptamer-chelated double emulsion that has the ability to actively target cancer cells and can be activated with ultrasound. AS1411, a 26-base guanine-rich oligonucleotide (GRO), was selected since AS1411 has the ability to target nucleolin surface receptors, which are overexpressed in many cancerous cell lines. Perfluorohexane forms the shell of the drug delivery vehicle since it is ultrasound-responsive in clinically acceptable pressure ranges. Ultrasound applied to double emulsions will cause vaporization of the perfluorocarbon shell, allowing transport of the molecular compound into the cancer cell with a higher efficiency. If a higher concentration is inside the cell than the microenvironment, the transient pores can release the molecular compound from the cytoplasm. This was seen in our static condition (p=0.054). A fluidic model is needed since static conditions doesn’t accurate depict conditions that will be seen in vivo. The payload was released from core of the double emulsion. To help reduce the passive release of the payload, different surfactants were testing. FluorN562 showed a slower release profile than FluorN561 and Poloxamer 188 at 4 oC, 21 oC, and 37 oC (poC being the optimal temperature for storage of double emulsions (p
Centner, Connor S, "Tumor-targeted double emulsions for ultrasound-triggered delivery of molecular therapeutics." (2018). Electronic Theses and Dissertations. Paper 3002.
Retrieved from https://ir.library.louisville.edu/etd/3002