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Membrane interactions of microgels as carriers of antimicrobial peptides

Nordström, Randi; Nyström, Lina; Andrén, Oliver C.J.; Malkoch, Michael; Umerska, Anita; Davoudi, Mina LU ; Schmidtchen, Artur LU and Malmsten, Martin (2018) In Journal of Colloid and Interface Science 513. p.141-150
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... (More)

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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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Antimicrobial peptide, Drug delivery, Lipid membrane, Microgel
in
Journal of Colloid and Interface Science
volume
513
pages
10 pages
publisher
Elsevier
external identifiers
  • scopus:85034020350
ISSN
0021-9797
DOI
10.1016/j.jcis.2017.11.014
language
English
LU publication?
yes
id
f2f41249-3918-4ed3-8c99-5178b75a7180
date added to LUP
2017-12-07 10:03:49
date last changed
2018-10-03 10:32:46
@article{f2f41249-3918-4ed3-8c99-5178b75a7180,
  abstract     = {<p>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.</p>},
  author       = {Nordström, Randi and Nyström, Lina and Andrén, Oliver C.J. and Malkoch, Michael and Umerska, Anita and Davoudi, Mina and Schmidtchen, Artur and Malmsten, Martin},
  issn         = {0021-9797},
  keyword      = {Antimicrobial peptide,Drug delivery,Lipid membrane,Microgel},
  language     = {eng},
  month        = {03},
  pages        = {141--150},
  publisher    = {Elsevier},
  series       = {Journal of Colloid and Interface Science},
  title        = {Membrane interactions of microgels as carriers of antimicrobial peptides},
  url          = {http://dx.doi.org/10.1016/j.jcis.2017.11.014},
  volume       = {513},
  year         = {2018},
}