uu.seUppsala University Publications
Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Avidin-biotin cross-linked microgel multilayers as carriers for antimicrobial peptides
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.ORCID iD: 0000-0001-5236-9107
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Farmakognosi.ORCID iD: 0000-0001-9070-6944
Show others and affiliations
2018 (English)In: Biomacromolecules, ISSN 1525-7797, E-ISSN 1526-4602, Vol. 19, no 12, p. 4691-4702Article in journal (Refereed) Published
Abstract [en]

Herein, we report on the formation of cross-linked antimicrobial peptide-loaded microgel multilayers. Poly(ethyl acrylate- co-methacrylic acid) microgels were synthesized and functionalized with biotin to enable the formation of microgel multilayers cross-linked with avidin. Microgel functionalization and avidin cross-linking were verified with infrared spectroscopy, dynamic light scattering, and z-potential measurements, while multilayer formation (up to four layers) was studied with null ellipsometry and quartz crystal microbalance with dissipation (QCM-D). Incorporation of the antimicrobial peptide KYE28 (KYEITTIHNLFRKLTHRLFRRNFGYTLR) into the microgel multilayers was achieved either in one shot after multilayer formation or through addition after each microgel layer deposition. The latter was found to strongly promote peptide incorporation. Further, antimicrobial properties of the peptide-loaded microgel multilayers against Escherichia coli were investigated and compared to those of a peptide-loaded microgel monolayer. Results showed a more pronounced suppression in bacterial viability in suspension for the microgel multilayers. Correspondingly, LIVE/DEAD staining showed promoted disruption of adhered bacteria for the KYE28-loaded multilayers. Taken together, cross-linked microgel multilayers thus show promise as high load surface coatings for antimicrobial peptides.

Place, publisher, year, edition, pages
2018. Vol. 19, no 12, p. 4691-4702
National Category
Pharmaceutical Sciences
Research subject
Pharmaceutical Physical Chemistry
Identifiers
URN: urn:nbn:se:uu:diva-361399DOI: 10.1021/acs.biomac.8b01484ISI: 000453109200018OAI: oai:DiVA.org:uu-361399DiVA, id: diva2:1250415
Funder
Swedish Research Council, 2016-05157Available from: 2018-09-24 Created: 2018-09-24 Last updated: 2019-01-15Bibliographically approved
In thesis
1. Microgels as Carriers for Antimicrobial Peptides: Surface-bound microgels, and factors affecting peptide interactions
Open this publication in new window or tab >>Microgels as Carriers for Antimicrobial Peptides: Surface-bound microgels, and factors affecting peptide interactions
2018 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

With a growing number of multi-resistant bacteria against conventional antibiotics, there is an urgent need to identify new antimicrobial therapeutics. One example that has gained considerable interest is antimicrobial peptides (AMPs). For AMPs to reach their full potential as therapeutics, as well as for other peptide and protein drugs, the right drug delivery system may overcome reported shortcomings, such as fast clearance in the bloodstream and proteolytic degradation. Microgels are weakly cross-linked polymer colloids, which can be made responsive to various stimuli. In the context of drug delivery, microgels are of particular interest as carriers for biomacromolecular drugs, such as peptides and proteins, as their water-rich environment offers both protection against enzymatic degradation and triggered release possibilities. Combining these, the aim of this thesis was to investigate electrostatically triggered surface-bound microgels as a delivery system for AMPs, as well as evaluate such systems as an antimicrobial and anti-inflammatory coating for biomaterials.

Results presented in this thesis demonstrate effects of microgel charge density, pH, and ionic strength on microgel volume transitions at solid interfaces, surface-induced microgel deformation and nanomechanical properties. In addition, effects of both microgel properties (charge density) and peptide properties (molecular weight, charge density, and posttranslational modifications) on peptide loading and release from surface-bound microgels were investigated. The presented thesis also reports in vitro studies of AMP-loaded microgels in dispersion and surface-bound, as either mono- or multilayers. Notably, the interplay between surface- and release-related effects for the antimicrobial properties of AMP-loaded microgels are investigated. In addition, anti-inflammatory properties of AMP-loaded microgels are also reported.

Taken together, microgels prove an interesting and versatile drug delivery system for AMPs. Results obtained in this thesis have demonstrated that several key factors need to be taken into consideration in the development of surface-bound microgels as a carrier for AMPs, and that small changes in microgel and peptide properties can alter peptide loading and release profiles.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2018. p. 66
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Pharmacy, ISSN 1651-6192 ; 259
Keywords
Antimicrobial peptides, Biomaterial coating, Drug delivery, Host defence peptides, Microgels, pH-responsive, Surface-bound
National Category
Pharmaceutical Sciences Biomaterials Science Physical Chemistry
Research subject
Pharmaceutical Physical Chemistry
Identifiers
urn:nbn:se:uu:diva-360241 (URN)978-91-513-0473-1 (ISBN)
Public defence
2018-11-30, A1:111a, BMC, Husargatan 3, Uppsala, 09:15 (English)
Opponent
Supervisors
Available from: 2018-11-09 Created: 2018-10-12 Last updated: 2018-11-19

Open Access in DiVA

No full text in DiVA

Other links

Publisher's full text

Authority records BETA

Nyström, LinaMalekkhaiat Häffner, SaraStrömstedt, Adam A.Browning, Kathryn L.Malmsten, Martin

Search in DiVA

By author/editor
Nyström, LinaMalekkhaiat Häffner, SaraStrömstedt, Adam A.Browning, Kathryn L.Malmsten, Martin
By organisation
Department of PharmacyFarmakognosi
In the same journal
Biomacromolecules
Pharmaceutical Sciences

Search outside of DiVA

GoogleGoogle Scholar

doi
urn-nbn

Altmetric score

doi
urn-nbn
Total: 114 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf