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Antimicrobial synergy of monolaurin lipid nanocapsules with adsorbed antimicrobial peptides against Staphylococcus aureus biofilms in vitro is absent in vivo
University of Groningen, Netherlands.
University of Groningen, Netherlands; Nankai University, China.
Université Bretagne, France.
Université de Nantes, France.
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2019 (English)In: Journal of Controlled Release, ISSN 0168-3659, E-ISSN 1873-4995, Vol. 293, p. 73-83Article in journal (Refereed) Published
Abstract [en]

Bacterial infections are mostly due to bacteria in their biofilm-mode of growth, while penetrability of antimicrobials into infectious biofilms and increasing antibiotic resistance hamper infection treatment. In-vitro, monolaurin lipid nanocapsules (ML-LNCs) carrying adsorbed antimicrobial peptides (AMPs) displayed synergistic efficacy against planktonic Staphylococcus aureus, but it has not been demonstrated, neither in-vitro nor in-vivo, that such ML-LNCs penetrate into infectious S. aureus biofilms and maintain synergy with AMPs. This study investigates the release mechanism of AMPs from ML-LNCs and possible antimicrobial synergy of ML-LNCs with the AMPs DPK-060 and LL-37 against S. aureus biofilms in-vitro and in a therapeutic, murine, infected wound-healing model. Zeta potentials demonstrated that AMP release from ML-LNCs was controlled by the AMP concentration in suspension. Both AMPs demonstrated no antimicrobial efficacy against four staphylococcal strains in a planktonic mode, while a checkerboard assay showed synergistic antimicrobial efficacy when ML-LNCs and DPK-060 were combined, but not for combinations of ML-LNCs and LL-37. Similar effects were seen for growth reduction of staphylococcal biofilms, with antimicrobial synergy persisting only for ML-LNCs at the highest level of DPK-060 or LL-37 adsorption. Healing of wounds infected with bioluminescent S. aureus Xen36, treated with ML-LNCs alone, was faster when treated with PBS, while AMPs alone did not yield faster wound-healing than PBS. Faster, synergistic wound-healing due to ML-LNCs with adsorbed DPK-060, was absent in-vivo. Summarizing, antimicrobial synergy of ML-LNCs with adsorbed antimicrobial peptides as seen in-vitro, is absent in in-vivo healing of infected wounds, likely because host AMPs adapted the synergistic role of the AMPs added. Thus, conclusions regarding synergistic antimicrobial efficacy, should not be drawn from planktonic data, while even in-vitro biofilm data bear little relevance for the in-vivo situation. © 2018

Place, publisher, year, edition, pages
2019. Vol. 293, p. 73-83
Keywords [en]
Antimicrobial peptides, Biofilms, Monolaurin, Nanocapsules, Wound-healing, Zeta potentials, Bacteria, Peptides, Suspensions (fluids), Zeta potential, Antibiotic resistance, Antimicrobial peptide, Antimicrobial synergies, Bacterial infections, Staphylococcal strains, Staphylococcus aureus, Wound healing
National Category
Natural Sciences
Identifiers
URN: urn:nbn:se:ri:diva-36563DOI: 10.1016/j.jconrel.2018.11.018Scopus ID: 2-s2.0-85057086211OAI: oai:DiVA.org:ri-36563DiVA, id: diva2:1270508
Note

 Funding details: 604182; Funding details: Seventh Framework Programme, FP7;

Available from: 2018-12-13 Created: 2018-12-13 Last updated: 2018-12-13Bibliographically approved

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