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Evaluation of cardiolipin-based vesicles as delivery vehicles for cationic amphiphilic peptides

Terrmin

HT23

Beskrivning

Cationic amphiphilic peptides have attracted considerable interest in novel pharmaceutical applications as they hold potential as a new class of antibiotics and anticancer agents. There, are, however, many challenges concerning the administration of these peptides. Peptides in free form are subject to rapid enzymatic degradation and fast renal filtrations. Formulating peptides in suitable nanoparticles, can help prevent both these effects. It has been shown, e.g., that melittin (a peptide isolated from honey bee venom) is protected against these detrimental effects if it is formulated into lipodisks (open lipid-bilayer nanostructures).
Cardiolipin is a natural occurring lipid found mainly in mitochondria membranes. The lipid is different from other phospholipids as it contains four fatty acid chains instead of only two. Due to this bulky hydrophobic component, cardiolipin has a tendency to induce the formation of inverted structures in spite of its highly charged headgroup. It has been shown previously that liposomes (i.e., lipid vesicles) formed by cardiolipin can be modified with large amounts of PEGylated lipids without compromising the integrity of the vesicle. Whereas liposomes built from most lipids transform into open structures by including 5 mol% or more PEG lipids, cardiolipin based vesicles maintained their closed structures with PEG lipid contents as high as 40 mol%.
Based on these observations, we hypothesize that cardiolipin-based liposomes should be able also to incorporate large amounts of melittin without compromising their structural integrity.
In this project you will characterize the binding and release behavior of melittin to and from cardiolipin-based liposomes. The studies will be based in steady-state fluorescence measurements. The results will allow evaluating whether cardiolipin based structures can be suitable delivery vehicles for cationic amphiphilic peptides.

Huvudområde

Farmaceutisk kemi

Ämne

Fysikalisk kemi

Typ

Laborativ studie

Företag

Uppsala Universitet

Ort/Plats

Uppsala

Handledarens namn

Victor Agmo Hernandez

Handledarens e-post

victor.agmo@ilk.uu.se

Institution

Institutionen för Läkemedelskemi

Program

Apotekarprogrammet

Kurs

Fördjupningsprojekt i farmaceutisk fysikalisk kemi 30 hp - 3FC290

Omfattning/hp

30hp