Thesis
Study of ultrasound-induced leakage from DOPC/DPPC/cholesterol model membranes
Master of Science (M.S.), Drexel University
Jun 2012
DOI:
https://doi.org/10.17918/etd-4128
Abstract
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 paper outlines a quantitative study of the controlled release of calcein from small unilamellar vesicles (SUVs) (~100nm) after exposure to low frequency ultrasound (LFUS). The SUVs 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 study how lipid composition and membrane phase behavior affect ultrasound-induced release of molecules encapsulated within the core of lipid vesicles. In this study, small unilamellar vesicles encapsulating fluorescent dye, calcein, were prepared by Rapid Solvent Exchange (RSE) technique. These lipid vesicles were exposed to ultrasound at a frequency of 24 kHz using a probe sonicator, at 30 sec time intervals followed by 3 min resting time. The leakage of calcein from the vesicles was then quantified by steady state fluorescence spectroscopy. Calcein release profiles obtained indicated that varying the molar amounts of cholesterol had different effects on the lipid membranes ability to resist leakage by ultrasound. Further studies were performed to investigate the effect that polyethylene glycol (PEG) has on ultrasound-mediated leakage of calcein from liposomes in the solid-ordered phase. Previous studies have shown that PEGylated liposomes are considered to be more susceptible to ultrasound. In this work, calcein leakage from liposomes that contained different molar quantities of DPPC and 1, 2 Distearoyl-Sn-Glycero-3-Phosphoethanolamin-N-methoxy(poly(ethylene glycol))2000 (DSPE-PEG2000) was analyzed and the results showed an increase in ultrasound-mediated leakage of calcein at 1% and 5% molar quantities of the polymer.
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Details
- Title
- Study of ultrasound-induced leakage from DOPC/DPPC/cholesterol model membranes
- Creators
- Maureen Wanjiku Waweru - DU
- Contributors
- Steven P. Wrenn (Advisor) - Drexel University (1970-)Peter Andreas Lewin (Advisor) - Drexel University (1970-)
- Awarding Institution
- Drexel University
- Degree Awarded
- Master of Science (M.S.)
- Publisher
- Drexel University; Philadelphia, Pennsylvania
- Resource Type
- Thesis
- Language
- English
- Academic Unit
- School of Biomedical Engineering, Science, and Health Systems (1997-2026); Drexel University
- Other Identifier
- 4128; 991014632070004721