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Lipid shell-enveloped polymeric nanoparticles with high integrity of lipid shells improve mucus penetration and interaction with cystic fibrosis-related bacterial biofilms

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Authors:
  • Wan, Feng ;
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    Drug Delivery and Biophysics of Biopharmaceuticals
  • Nylander, Tommy ;
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    unknown
  • Klodzinska, Sylvia Natalie ;
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    Orcid logo0000-0001-7443-2234
    Drug Delivery and Biophysics of Biopharmaceuticals
  • Foged, Camilla ;
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    Orcid logo0000-0003-2812-5588
    Vaccine Design and Delivery
  • Yang, Mingshi ;
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    Orcid logo0000-0003-3201-4696
    Manufacturing and Materials
  • Baldursdottir, Stefania G ;
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    Manufacturing and Materials
  • Mørck Nielsen, Hanne
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    Orcid logo0000-0002-7285-9100
    Drug Delivery and Biophysics of Biopharmaceuticals
DOI:
10.1021/acsami.7b19762
Abstract:
Nanoparticle (NP) mediated drug delivery into viscous biomatrices, e.g., mucus and bacterial biofilms, is challenging. Lipid shell-enveloped polymeric NPs (Lipid@NPs), composed of a polymeric NP core coated with a lipid shell, represent a promising alternative to the current delivery systems. Here, we describe facile methods to prepare Lipid@NPs with high integrity of lipid shells and demonstrate the potential of Lipid@NPs in effective mucus penetration and interaction with cystic fibrosis-related bacterial biofilms. Lipid shell-enveloped polystyrene NPs with high integrity of lipid shells (cLipid@PSNPs) were prepared by using an electrostatically mediated layer-by-layer approach, where the model polystyrene NPs (PSNPs) were first modified with positively charged poly-L-lysine (PLL) and 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP), followed by subsequent fusion with zwitterionic, PEGylated small unilamellar vesicles (SUVs). The interaction of the PSNPs with SUVs was significantly enhanced by modifying the PSNPs with PLL and DOTAP, which eventually resulted in the formation of cLipid@PSNPs, i.e. Lipid@PLL-PSNPs and Lipid@DOTAP-PSNPs. Improved mucus-penetrating property of cLipid@PSNPs was demonstrated by quartz crystal microbalance with dissipation monitoring measurements. Furthermore, fluorescence resonance energy transfer measurements showed that the interaction of the cLipid@PSNPs with bacterial biofilms was significantly promoted. In conclusion, we prepare cLipid@PSNPs via an electrostatically mediated layer-by layer approach. Our results suggest that the integrity of the lipid envelopes is crucial for enabling the diffusion of Lipid@PSNPs into the mucus layer and promoting the interaction of Lipid@PSNPs with a bacterial biofilm.
Type:
Journal article
Language:
English
Published in:
A C S Applied Materials and Interfaces, 2018, Vol 10, Issue 13, p. 10678-10687
Keywords:
Journal Article
Main Research Area:
Medical science
Publication Status:
Published
Review type:
Peer Review
Submission year:
2018
Scientific Level:
Scientific
ID:
2396706091

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