Interactions of Miltefosine and Phospholipid DPPC at the Air/Water Interface
Wildgen, Sarah M.
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Several Langmuir monolayer studies have suggested that the drug Hexadecylphosphocholine (miltefosine) has a mode of action which is directly related to the cell membrane. Because the exact mode of action still unknown, the current study was aimed at examining the interaction of miltefosine and phospholipids. Specifically, the interaction of the phospholipid 1,2-Dihexadecanoyl-sn-glycero-3- phosphocholine (DPPC) and miltefosine was investigated. Pure surface pressure-area (pi) isotherms of each component were obtained and analyzed through compression modulus (Cs- 1). Solutions analyzed were DPPC and miltefosine mixed monolayer solutions of 0.25, 0.40, 0.50, 0.60, 0.75, 0.82, and 0.90 XDPPC. The films were spread at room temperature on an ultra pure water subphase. Surface pressure area (pi) isotherms of the various mixed monolayer solution concentrations were recorded and characterized. Interactions of the molecules were analyzed through mean molecular area (A12) plots, and quantified through calculated excess free energy of mixing (Aexc) values. The results indicated DPPC and miltefosine mixed monolayers showed slight miscible behavior was seen due to the small deviations from ideality at low concentrations of DPPC. At higher concentrations and pressures, the DPPC and miltefosine monolayers showed positive deviations. This can be interpreted as being caused by a change in orientation of the polar groups during the compression of the monolayer and a result of the double bond in the hydrocarbon tail of the DPPC molecule.
Advisor: Maria Bohorquez