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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

Wan, Feng ; Nylander, Tommy LU ; Klodzinska, Sylvia Natalie ; Foged, Camilla ; Yang, Mingshi ; Baldursdottir, Stefania G. and Nielsen, Hanne M. (2018) In ACS Applied Materials and Interfaces 10(13). p.10678-10687
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 the facile methods to prepare Lipid@NPs with high integrity of lipid shells and demonstrate the potential of Lipid@NPs in an 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... (More)

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 the facile methods to prepare Lipid@NPs with high integrity of lipid shells and demonstrate the potential of Lipid@NPs in an 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 prepared 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.

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author
; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
bacterial biofilm, FRET, lipid bilayer-enveloped polymeric NPs, nanomedicines, Pseudomonas aeruginosa, QCM-D
in
ACS Applied Materials and Interfaces
volume
10
issue
13
pages
10 pages
publisher
The American Chemical Society (ACS)
external identifiers
  • pmid:29473725
  • scopus:85044972827
ISSN
1944-8244
DOI
10.1021/acsami.7b19762
language
English
LU publication?
yes
id
76851fe9-0e68-473b-bc21-adb99f3a5f5b
date added to LUP
2018-04-18 16:11:01
date last changed
2024-03-18 08:30:15
@article{76851fe9-0e68-473b-bc21-adb99f3a5f5b,
  abstract     = {{<p>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 the facile methods to prepare Lipid@NPs with high integrity of lipid shells and demonstrate the potential of Lipid@NPs in an 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 prepared 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.</p>}},
  author       = {{Wan, Feng and Nylander, Tommy and Klodzinska, Sylvia Natalie and Foged, Camilla and Yang, Mingshi and Baldursdottir, Stefania G. and Nielsen, Hanne M.}},
  issn         = {{1944-8244}},
  keywords     = {{bacterial biofilm; FRET; lipid bilayer-enveloped polymeric NPs; nanomedicines; Pseudomonas aeruginosa; QCM-D}},
  language     = {{eng}},
  month        = {{04}},
  number       = {{13}},
  pages        = {{10678--10687}},
  publisher    = {{The American Chemical Society (ACS)}},
  series       = {{ACS Applied Materials and Interfaces}},
  title        = {{Lipid Shell-Enveloped Polymeric Nanoparticles with High Integrity of Lipid Shells Improve Mucus Penetration and Interaction with Cystic Fibrosis-Related Bacterial Biofilms}},
  url          = {{http://dx.doi.org/10.1021/acsami.7b19762}},
  doi          = {{10.1021/acsami.7b19762}},
  volume       = {{10}},
  year         = {{2018}},
}