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Membrane interactions of microgels as carriers of antimicrobial peptides
KTH, School of Chemical Science and Engineering (CHE), Fibre and Polymer Technology.
KTH, School of Chemical Science and Engineering (CHE), Fibre and Polymer Technology.ORCID iD: 0000-0002-9200-8004
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2018 (English)In: Journal of Colloid and Interface Science, ISSN 0021-9797, E-ISSN 1095-7103, Vol. 513, p. 141-150Article in journal (Refereed) Published
Abstract [en]

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. 

Place, publisher, year, edition, pages
Academic Press Inc. , 2018. Vol. 513, p. 141-150
Keywords [en]
Antimicrobial peptide, Drug delivery, Lipid membrane, Microgel, Bacteria, Charge density, Circular dichroism spectroscopy, Dichroism, Drug interactions, Escherichia coli, Gels, Light scattering, Membranes, Microorganisms, Polypeptides, Anti-microbial effects, Cationic antimicrobial peptides, Lipid membranes, Methicillin-resistant staphylococcus aureus, Nanoparticle tracking analysis, Pseudomonas aeruginosa, Peptides, anion, cathelicidin antimicrobial peptide LL 37, cation, dpk 060, drug carrier, poly(acrylate methacrylate), poly(ethyl methacrylate), polypeptide antibiotic agent, proteinase, triton x 100, unclassified drug, adsorption kinetics, analytic method, aqueous solution, Article, bacterial membrane, bactericidal activity, binding kinetics, cell interaction, circular dichroism, conformational transition, controlled study, cytotoxicity, drug delivery system, drug distribution, drug release, electrical parameters, ellipsometry, erythrocyte, gel, hemolysis assay, hydrophobicity, in vitro study, ionic strength, membrane damage, methicillin resistant Staphylococcus aureus, minimum inhibitory concentration, nanoencapsulation, nonhuman, particle size, photon correlation spectroscopy, priority journal, protein degradation, protein secretion, protein stability, static electricity, zeta potential
National Category
Chemical Sciences
Identifiers
URN: urn:nbn:se:kth:diva-223121DOI: 10.1016/j.jcis.2017.11.014Scopus ID: 2-s2.0-85034020350OAI: oai:DiVA.org:kth-223121DiVA, id: diva2:1193632
Note

Export Date: 13 February 2018; Article; CODEN: JCISA; Correspondence Address: Nordström, R.; Department of Pharmacy, Uppsala UniversitySweden; email: randi.nordstrom@farmaci.uu.se; Funding details: 604182. QC 20180327

Available from: 2018-03-27 Created: 2018-03-27 Last updated: 2018-03-27Bibliographically approved

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Andrén, Oliver C. J.Malkoch, Michael

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