Membrane interactions of microgels as carriers of antimicrobial peptides

Research output: Contribution to journalArticle

Abstract

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.

Details

Authors
  • Randi Nordström
  • Lina Nyström
  • Oliver C.J. Andrén
  • Michael Malkoch
  • Anita Umerska
  • Mina Davoudi
  • Artur Schmidtchen
  • Martin Malmsten
Organisations
External organisations
  • Uppsala University
  • KTH Royal Institute of Technology
  • Nanyang Technological University
  • University of Copenhagen
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Medical Materials
  • Pharmaceutical Sciences

Keywords

  • Antimicrobial peptide, Drug delivery, Lipid membrane, Microgel
Original languageEnglish
Pages (from-to)141-150
Number of pages10
JournalJournal of Colloid and Interface Science
Volume513
Publication statusPublished - 2018 Mar 1
Publication categoryResearch
Peer-reviewedYes