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dc.contributor.advisorDea, Pheobe
dc.contributor.authorTran, Rosalie 0:00
dc.description.abstractThe effects of varying concentrations of the antipsychotic drug, chlorpromazine hydrochloride (CPZ), on the phase behavior of dipalmitoylphosphatidylcholine (DPPC), a 16-carbon acyl chain phospholipid, have been investigated by fluorescence spectroscopy and differential scanning calorimetry (DSC). Results confirmed that the incorporation of the amphiphilic drug into the bilayer began to dramatically affect its fluidity as low as 2 mol% CPZ. With increasing concentrations of CPZ, the pre- and main transition temperatures of DPPC decreased. These thermal shifts demonstrated that the interaction of the tricyclic ring on CPZ with the lipid headgroups disordered the acyl chains of DPPC upon incorporation such that it favors the liquid crystalline phase over the gel phase. Fluorescence anisotropy was used to monitor the rotation of CPZ in the bilayer and estimate the microviscosity of DPPC. Results show that the hydrocarbon chain regions near CPZ became more fluid and disordered with higher mole percentages. The sub- and pretransition peaks disappeared in the presence of 5 mol% CPZ and above, indicating a direct transition from planar gel to the liquid crystalline phase upon destabilization of the subgel and rippled gel phases. Near 30 mol% CPZ, the appearance of a peak at ~33?C suggested the induction and stabilization of the interdigitated phase with the introduction of higher amounts of CPZ. Ultimately, the fluorescence emission spectra of CPZ seemed to depend on the hydration of DPPC, the amount of CPZ present, and the partitioning of the drug into the lipid bilayer.
dc.description.sponsorshipDepartment of Education (GAANN) Fellowship
dc.titleFluorescence and Calorimetry Studies of Drug Interactions with Lipid Bilayers.

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