VT22
How do ionic drugs are transported across cell membranes? This question is still not convincingly answered in spite of its high relevance: most therapeutic drugs are charged at physiological pH.. How these drugs partition and diffuse through the cell membrane is still a matter of debate. A novel experimental technique developed in our laboratory can provide with insight about how ionic drugs partition into lipid membranes. The method is based on supported electroactive lipid bilayers. Upon oxidation or reduction of an electroactive probe embedded in the lipid bilayer, ionic drugs will be transferred into the membrane interior. The potential at which this process occurs can be related to the standard partition coefficient of the drug, independently of what other ions are present in solution.
In this project you will develop methods to produce electroactive supported lipid bilayers of various biologically relevant compositions on different supports (mainly gold and indium-tin oxide). These structures will then be used to characterize the membrane-partition behavior of reference ions and of relevant therapeutic ionic drugs. You will use electroanalytical techniques (mainly electrochemical impedance spectroscopy (EIS) and cyclic voltammetry) in combination with the quartz crystal microbalance with dissipation monitoring (QCM-D). Complementary techniques as dynamic light scattering (DLS) and Cryo-TEM may also be used.
Farmaceutisk kemi
Fysikalisk kemi
Laborativ studie
Institutionen för Läkemedelskemi, UU
Uppsala
Víctor Agmo Hernández
victor.agmo@ilk.uu.se
30hp
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