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Peptide-Loaded Cubosomes Functioning as an Antimicrobial Unit against Escherichia coli
RISE - Research Institutes of Sweden, Bioscience and Materials, Surface, Process and Formulation. Chalmers University of Technology, Sweden.ORCID iD: 0000-0003-4742-1702
University of Copenhagen, Denmark.
Uppsala University, Sweden.
Rutherford Appleton Laboratory, UK.
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2019 (English)In: ACS Applied Materials and Interfaces, ISSN 1944-8244, E-ISSN 1944-8252, Vol. 11, no 24, p. 21314-21322Article in journal (Refereed) Published
Abstract [en]

Dispersions of cubic liquid crystalline phases, also known as cubosomes, have shown great promise as delivery vehicles for a wide range of medicines. Due to their ordered structure, comprising alternating hydrophilic and hydrophobic domains, cubosomes possess unique delivery properties and compatibility with both water-soluble and -insoluble drugs. However, the drug delivery mechanism and cubosome interaction with human cells and bacteria are still poorly understood. Herein, we reveal how cubosomes loaded with the human cathelicidin antimicrobial peptide LL-37, a system with high bacteria-killing effect, interact with the bacterial membrane and provide new insights into the eradication mechanism. Combining the advanced experimental techniques neutron reflectivity and quartz crystal microbalance with dissipation monitoring, a mechanistic drug delivery model for LL-37-loaded cubosomes on bacterial mimicking bilayers was constructed. Moreover, the cubosome interaction with Escherichia coli was directly visualized using super-resolution laser scanning microscopy and cryogenic electron tomography. We could conclude that cubosomes loaded with LL-37 adsorbed and distorted bacterial membranes, providing evidence that the peptide-loaded cubosomes function as an antimicrobial unit.

Place, publisher, year, edition, pages
American Chemical Society , 2019. Vol. 11, no 24, p. 21314-21322
Keywords [en]
antimicrobial peptide, bacteria, cubosome, LL-37, membrane, Controlled drug delivery, Electric impedance tomography, Escherichia coli, Membranes, Peptides, Targeted drug delivery, Cubosomes, Experimental techniques, Hydrophilic and hydrophobic, Laser scanning microscopy, Liquid-crystalline phasis, Quartz crystal microbalance with dissipation monitoring, Drug interactions
National Category
Natural Sciences
Identifiers
URN: urn:nbn:se:ri:diva-39268DOI: 10.1021/acsami.9b01826Scopus ID: 2-s2.0-85067578230OAI: oai:DiVA.org:ri-39268DiVA, id: diva2:1334703
Note

Funding details: MAX4ESSFUN, 2016-11-01, CTH-009; Funding details: 604182; Funding text 1: The authors thank Carolina Tangemö at the Centre for Cellular Imaging (CCI, University of Gothenburg, Sweden), Camilla Holmlund at Umeå core facility for electron microscopy (Umeå University, Sweden), and the National Microscopy Infrastructure, NMI (VR-RFI 2016-00968) for providing assistance in high-resolution confocal and cryogenic electron microscopy imaging. ISIS Neutron and Muon Source, Rutherford Appleton Laboratory, Didcot, U.K. (RB number: 1810031 DOI:10.5286/ISIS.E.92922658) is acknowledged for beamtime allocation from the Science and Technology Facilities Council. Adrian Rennie (Uppsala University, Sweden) is greatly acknowledged for fruitful discussions about NR data. Financial support was obtained from the European Union’s Seventh Framework Program grant agreement No. 604182 within the FORMAMP project (L.B and L.R. and R.N.) and from RISE Research Institutes of Sweden (Stockholm, Sweden) (L.B., L.R., M.H., and J.S.-C.). Financial support is also acknowledged from the LEO Foundation Center for Cutaneous Drug Delivery (grant number 2016-11-01; K.L.B. and L.S.E.D.) and MAX4ESSFUN (grant number CTH-009; L.B., K.L.B., and M.A.).

Available from: 2019-07-03 Created: 2019-07-03 Last updated: 2019-08-07Bibliographically approved

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