CONICET PhD fellow (Latin American countries)
Director: Maria Laura Fanani
PhD Thesis Topic
Interaction of amphiphilic drugs with model lipidic membranes
This plan focuses on the study of the interaction of amphiphilic drugs with pharmacological interest with model lipid membranes as lipid monolayers and liposomes of different characteristics. The drugs studied, miltefosine and edelfosine, belong to the families of the alkylphosphocholines and alkyl-lysophospholipids. These surface active, sparingly soluble in water compounds are currently used as anticancer drug and against diseases such as leishmaniasis. The mechanism of action of these drugs, although not completely elucidated, must be related to lipid homeostasis of the biological membrane, which leads to apoptosis. Notable is the finding that in vivo these drugs selectively target cancer with little effect on normal cells, raising the question of what would be sensing these drugs when are incorporated into various types of membranes. To explore this issue we propose to study the interaction of miltefosine and edelfosine with model membranes having different lipid phases with different structural and rheological properties. Using membranes containing sphingomyelin, phosphatidylcholine and cholesterol in different proportions allows explore three different lipid phase states, relevant to the biological function of membrane: liquid-expanded, liquid-condensed or liquid-ordered membranes. Furthermore, they can show phase coexistence with the presence of a lipid domains. We will also explore lipid mixtures that constitute a simple system to simulate the properties of the stratum corneum of skin.