Membrane interactions of microgels as carriers of antimicrobial peptides

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TitreMembrane interactions of microgels as carriers of antimicrobial peptides
Type de publicationArticle de revue
AuteurNordström, Randi, Nyström, Lina, Andrén, Oliver CJ, Malkoch, Michael, Umerska, Anita , Davoudi, Mina, Schmidtchen, Artur, Malmsten, Martin
TypeArticle scientifique dans une revue à comité de lecture
Date1er Mars 2018
Titre de la revueJournal of Colloid and Interface Science
Mots-clésAntimicrobial peptide, drug delivery, Lipid membrane, Microgel
Résumé en anglais

Microgels are interesting as potential delivery systems for antimicrobial peptides. In order to elucidate membrane interactions of such systems, we here investigate effects of microgel charge density on antimicrobial peptide loading and release, as well as consequences of this for membrane interactions and antimicrobial effects, using ellipsometry, circular dichroism spectroscopy, nanoparticle tracking analysis, dynamic light scattering and z-potential measurements. Anionic poly(ethyl acrylate-co-methacrylic acid) microgels were found to incorporate considerable amounts of the cationic antimicrobial peptides LL-37 (LLGDFFRKSKEKIGKEFKRIVQRIKDFLRNLVPRTES) and DPK-060 (GKHKNKGKKNGKHNGWKWWW) and to protect incorporated peptides from degradation by infection-related proteases at high microgel charge density. As a result of their net negative z-potential also at high peptide loading, neither empty nor peptide-loaded microgels adsorb at supported bacteria-mimicking membranes. Instead, membrane disruption is mediated almost exclusively by peptide release. Mirroring this, antimicrobial effects against several clinically relevant bacteria (methicillin-resistant Staphylococcus aureus (MRSA), Escherichia coli, and Pseudomonas aeruginosa) were found to be promoted by factors facilitating peptide release, such as decreasing peptide length and decreasing microgel charge density. Microgels were further demonstrated to display low toxicity towards erythrocytes. Taken together, the results demonstrate some interesting opportunities for the use of microgels as delivery systems for antimicrobial peptides, but also highlight several key factors which need to be controlled for their successful use

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Titre abrégéJournal of Colloid and Interface Science