1. Membrane interactions of microgels as carriers of antimicrobial peptides
- Author
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Anita-Monika Umerska, Randi Nordström, Mina Davoudi, Michael Malkoch, Oliver C. J. Andrén, Lina Nyström, Artur Schmidtchen, Martin Malmsten, Fiber and Polymer Technology, Royal Institute of Technology, Royal Institute of Technology [Stockholm] (KTH ), Micro et Nanomédecines Translationnelles (MINT), and Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)
- Subjects
Circular dichroism ,Surface Properties ,[SDV]Life Sciences [q-bio] ,Antimicrobial peptides ,Peptide ,02 engineering and technology ,010402 general chemistry ,Physical Chemistry ,01 natural sciences ,Biomaterials ,Cell membrane ,Colloid and Surface Chemistry ,Lipid membrane ,medicine ,Lipid bilayer ,Fysikalisk kemi ,chemistry.chemical_classification ,Bacteria ,Chemistry ,Cell Membrane ,021001 nanoscience & nanotechnology ,Antimicrobial ,Anti-Bacterial Agents ,0104 chemical sciences ,Surfaces, Coatings and Films ,Electronic, Optical and Magnetic Materials ,medicine.anatomical_structure ,Membrane ,Biochemistry ,Drug delivery ,drug delivery ,Biophysics ,Microgel ,0210 nano-technology ,Antimicrobial peptide ,Gels ,Antimicrobial Cationic Peptides - Abstract
International audience; 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
- Published
- 2018
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