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ENCAPSULATION OF TAXOL FOR USE IN VESICLE BASED DRUG DELIVERY SYSTEMS Background: Taxol is an important drug used in the treatment of breast, ovarian, lung, head and neck cancers. However, the drug?s hydrophobic nature has made this drug very difficult to administer. Currently, Taxol is delivered intravenously in a toxic mixture of Cremophore/Ethanol. In addition to harmful side effects, this method of drug delivery has poor drug circulation time and allows uncontrolled circulation of the drug throughout the body. Encapsulation of Taxol in a phospholipid bilayer vesicle has the potential to greatly improve the current methods of drug administration. The bilayer membrane would eliminate the use of the Cremophore/Ethanol cocktail, provide a protective barrier between the drug and the body increasing drug circulation time and decreasing drug interaction with healthy cells, and provide a vehicle capable of cell targeting and controlled release. Methods: A solution of Taxol in 100% ethanol was added to L-alpha-Dipalmitoyl phosphatidylcholine (DPPC) then dialyzed and heated past the melting temperature of DPPC. Freeze fracture replicas of the dialyzed product were imaged by a transmission electron microscope for evidence of vesicle formation. Chromatography(SEC), fluorescence and UV/VIS spectroscopy were used to isolate and determine the location of free taxol, encapsulated taxol and encapsulation efficiency. Results: Freeze fracture images revealed vesicle formation in the presence of Taxol. A rippled phase was observed in vesicles formed from the solution with Taxol. The rippled phase is evidence of a change in lipid phase behavior, possibly due to an interaction with Taxol. Vesicles were isolated from the solution using size-exclusion chromatography (SEC) and identified using fluorescence spectroscopy. UV/VIS spectroscopic data is currently being collected. UV/VIS will be performed on fractions collected by SEC to determine the amount of free taxol. Vesicle containing fractions will then be treated with detergent to liberate any encapsulated taxol and will be measured by UV/VIS. Future Projects: Future projects will include: the completion of the UV/VIS portion of the experiment, improvement of separation techniques to collect free Taxol, and the refinement of the dialysis method to optimize Taxol encapsulation.
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