349600 A Dynamic, Non-Sink Ultrafiltration Method of Determining Dexamethasone Phosphate Liposome Permeability

Monday, November 4, 2013
Grand Ballroom B (Hilton)
Amy Allen1, Kyle Fugit2, Tian-Xiang Xiang2, Thomas Dziubla3 and Bradley D. Anderson2, (1)Chemical and Biomolecular Engineering, North Carolina State University, Holly Springs, NC, (2)Pharmaceutical Sciences, University of Kentucky, Lexington, KY, (3)Chemical and Materials Engineering, University of Kentucky, Lexington, KY

When used as a drug delivery mechanism, liposomes are able to increase the amount of drug delivered to cancerous tissue by the EPR effect. To effectively use liposomes for this purpose it is essential to understand the kinetics of drug permeation through the lipid bilayer. Currently, these data cannot be predicted quantitatively and are most commonly tested using dynamic dialysis. This method is accurate when the release rate is slower than the permeation through the dialysis membrane; however, when the release rate is similar to or faster than the rate of drug permeation though the membrane it is no longer possible to get statistically significant data about the transport kinetics. In cases such as this a new method is needed. This work employs a dynamic, non-sink ultrafiltration method that removes the rate limiting dialysis membrane. Studies using this method were done on the transport of dexamethasone phosphate across DPPC lipid bilayers. The results of these experiments showed an initial plateau having a lag time of 10-20 hours before any release was evident. The cause for this observation is still unexplained.

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