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Ultrasound-mediated leakage from DMPC-cholesterol model membrane Stephanie Alyssa Toth Advisor: Dr. Steven Wrenn The application of ultrasound for targeted drug delivery offers a convenient, universal, and affordable method for drug delivery. Targeted drug delivery through the use of lipid vesicles coupled with ultrasound is beneficial for the treatment of diseases because it reduces the amount of effective dosage necessary and toxic side effects compared to traditional systemic treatments. Ultrasound-mediated leakage from model membranes occurs when the lipid vesicles are exposed to low ultrasound frequencies of approximately 20 kHz which causes transient cavitation of gaseous voids in the sample. This work investigated a binary, DMPC-cholesterol, model membrane to study the effects of lipid composition and lipid phase behavior on vesicle leakage by ultrasound. A self-quenching dye, calcein, was encapsulated within the aqueous core of lipid vesicles. These vesicles were exposed to ultrasound at a frequency of 20 kHz via a probe tip transducer in small intervals with resting time. Steady state fluorescence spectroscopy was used to quantify the dye leakage resultant from the exposure to ultrasound. Leakage profiles obtained indicate that different mole fractions of cholesterol have different effects on the membrane’s ability to resist leakage by ultrasound.