Master's Thesis Defense - Study of Ultrasound-Induced Leakage from DOPC/DPPC/Cholesterol Model Membranes
Date: June 5, 2012
Time: 10:00 AM
Location: Bossone Research Enterprise Center, Room: 709
Speaker(s):
Maureen W. Waweru
Advisors: Steven P. Wrenn, Ph.D., and Peter A. Lewin, Ph.D.
Details:
Ultrasound-mediated controlled drug release is beneficial because it is a non invasive process that is effective in the treatment of diseases, and which minimizes toxic side effects that are common with other systemic treatments. As a model for the application of ultrasound in drug delivery, this study outlines a quantitative analysis of the controlled release of calcein from large unilamellar vesicles (LUVs) (>100nm) after exposure to low frequency ultrasound (LFUS). The LUVs comprise of varying compositions of 1, 2-dioleoyl-phosphocholine (DOPC), 1, 2-dipaltimoyl-phosphocholine (DPPC), and cholesterol.
Together, these compounds provide a model lipid membrane system that can be used to investigate how lipid composition and membrane phase behavior affect ultrasound-induced release of molecules encapsulated within the core of lipid vesicles. In this study, large unilamellar vesicles encapsulating fluorescent dye, calcein, were prepared by Rapid Solvent Exchange (RSE) method. These lipid vesicles were exposed to ultrasound at a frequency of 24 kHz using a probe sonicator, for 30s bursts followed by 3 min resting time for a total of 22 min. The leakage of calcein from the vesicles was then quantified by steady state fluorescence spectroscopy. Calcein release profiles obtained indicated that lipid composition and phase behavior do influence ultrasound-mediated leakage.
Further studies were performed to investigate the effect that polyethylene glycol (PEG) has on ultrasound-mediated leakage of calcein from lipid vesicles. Previous studies have shown that PEGylated liposomes are considered to be more susceptible to ultrasound. In this work, leakage from solid-ordered phase liposomes that contained molar quantities of 5 % and less of 1, 2 Distearoyl-Sn-Glycero-3-Phosphoethanolamin-N-methoxy(poly(ethyleneglycol)2000 (DSPE-PEG2000) displayed an increase in ultrasound-mediated leakage of calcein.
Biosketch:
Directions:
The Bossone Research Enterprise Center is located at the corner of 32nd and Market Streets.
|
