Evaluation of anionic vesicles as delivery vehicles for antimicrobial peptides

Terrmin

HT25

Beskrivning

Cationic amphiphilic peptides (CAPs) 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).
Previous results from our laboratory suggest that liposomes based on cardiolipin (an anionic phospholipid found mainly in the inner membrane of heart mitochondria) present several advantages as delivery vehicles for CAPs. Cardiolipin, however, is not optimal for drug-delivery applications given its relatively high price and low chemical stability. The objective of this project is to investigate whether cardiolipin can be substituted by other more accessible and stable anionic phospholipids (mainly phosphatidylglycerol lipids).
In this project you will further characterize the binding and release behavior of melittin to and from anionic liposomes based on phosphatidylglycerol and compare the results with what has been obtained previously using cardiolipin-based liposomes. The studies will be based in steady-state fluorescence measurements. The results will allow evaluating whether cardiolipin can be replaced with other anionic phospholipids in order to design 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

Hur många studenter kan antagas för detta projekt?

1

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