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Ultrasmall TPGS-PLGA Hybrid Nanoparticles for Site-Specific Delivery of Antibiotics into Pseudomonas aeruginosa Biofilms in Lungs

Wan, Feng ; Bohr, Søren S.R. ; Kłodzińska, Sylvia Natalie ; Jumaa, Haidar ; Huang, Zheng ; Nylander, Tommy LU ; Thygesen, Mikkel Boas ; Sørensen, Kasper Kildegaard ; Jensen, Knud Jørgen and Sternberg, Claus , et al. (2020) In ACS Applied Materials and Interfaces 12(1). p.380-389
Abstract

Inhaled antibiotic treatment of cystic fibrosis-related bacterial biofilm infections is challenging because of the pathological environment of the lungs. Here, we present an "environment-adaptive" nanoparticle composed of a solid poly lactic-co-glycolic acid (PLGA) core and a mucus-inert, enzymatically cleavable shell of d-α-tocopheryl polyethylene glycol 1000 succinate (TPGS) for the site-specific delivery of antibiotics to bacterial biofilms via aerosol administration. The hybrid nanoparticles with ultrasmall size were self-assembled via a nanoprecipitation process by using a facile microfluidic method. The interactions of the nanoparticles with the biological barriers were comprehensively investigated by using cutting-edge techniques... (More)

Inhaled antibiotic treatment of cystic fibrosis-related bacterial biofilm infections is challenging because of the pathological environment of the lungs. Here, we present an "environment-adaptive" nanoparticle composed of a solid poly lactic-co-glycolic acid (PLGA) core and a mucus-inert, enzymatically cleavable shell of d-α-tocopheryl polyethylene glycol 1000 succinate (TPGS) for the site-specific delivery of antibiotics to bacterial biofilms via aerosol administration. The hybrid nanoparticles with ultrasmall size were self-assembled via a nanoprecipitation process by using a facile microfluidic method. The interactions of the nanoparticles with the biological barriers were comprehensively investigated by using cutting-edge techniques (e.g., quartz crystal microbalance with dissipation monitoring, total internal reflection fluorescence microscopy-based particle tracking, in vitro biofilm model cultured in a flow-chamber system, and quantitative imaging analysis). Our results suggest that the mucus-inert, enzymatically cleavable TPGS shell enables the nanoparticles to penetrate through the mucus, accumulate in the deeper layer of the biofilms, and serve as sustained release depot, thereby improving the killing efficacy of azithromycin (a macrolide antibiotic) against biofilm-forming Pseudomonas aeruginosa. In conclusion, the ultrasmall TPGS-PLGA hybrid nanoparticles represent an efficient delivery system to overcome the multiple barriers and release antibiotics in a sustained manner in the vicinity of the biofilm-forming bacteria.

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publication status
published
subject
keywords
aerosol administration, bio-nano interaction, cystic fibrosis, Pseudomonas aeruginosa biofilm, TPGS-PLGA hybrid nanoparticles
in
ACS Applied Materials and Interfaces
volume
12
issue
1
pages
380 - 389
publisher
The American Chemical Society (ACS)
external identifiers
  • pmid:31804792
  • scopus:85077111358
ISSN
1944-8244
DOI
10.1021/acsami.9b19644
language
English
LU publication?
yes
id
46c2fdb7-e4db-4581-ba69-55a77a9223e3
date added to LUP
2020-01-17 11:56:35
date last changed
2020-01-18 03:00:04
@article{46c2fdb7-e4db-4581-ba69-55a77a9223e3,
  abstract     = {<p>Inhaled antibiotic treatment of cystic fibrosis-related bacterial biofilm infections is challenging because of the pathological environment of the lungs. Here, we present an "environment-adaptive" nanoparticle composed of a solid poly lactic-co-glycolic acid (PLGA) core and a mucus-inert, enzymatically cleavable shell of d-α-tocopheryl polyethylene glycol 1000 succinate (TPGS) for the site-specific delivery of antibiotics to bacterial biofilms via aerosol administration. The hybrid nanoparticles with ultrasmall size were self-assembled via a nanoprecipitation process by using a facile microfluidic method. The interactions of the nanoparticles with the biological barriers were comprehensively investigated by using cutting-edge techniques (e.g., quartz crystal microbalance with dissipation monitoring, total internal reflection fluorescence microscopy-based particle tracking, in vitro biofilm model cultured in a flow-chamber system, and quantitative imaging analysis). Our results suggest that the mucus-inert, enzymatically cleavable TPGS shell enables the nanoparticles to penetrate through the mucus, accumulate in the deeper layer of the biofilms, and serve as sustained release depot, thereby improving the killing efficacy of azithromycin (a macrolide antibiotic) against biofilm-forming Pseudomonas aeruginosa. In conclusion, the ultrasmall TPGS-PLGA hybrid nanoparticles represent an efficient delivery system to overcome the multiple barriers and release antibiotics in a sustained manner in the vicinity of the biofilm-forming bacteria.</p>},
  author       = {Wan, Feng and Bohr, Søren S.R. and Kłodzińska, Sylvia Natalie and Jumaa, Haidar and Huang, Zheng and Nylander, Tommy and Thygesen, Mikkel Boas and Sørensen, Kasper Kildegaard and Jensen, Knud Jørgen and Sternberg, Claus and Hatzakis, Nikos and Mørck Nielsen, Hanne},
  issn         = {1944-8244},
  language     = {eng},
  number       = {1},
  pages        = {380--389},
  publisher    = {The American Chemical Society (ACS)},
  series       = {ACS Applied Materials and Interfaces},
  title        = {Ultrasmall TPGS-PLGA Hybrid Nanoparticles for Site-Specific Delivery of Antibiotics into Pseudomonas aeruginosa Biofilms in Lungs},
  url          = {http://dx.doi.org/10.1021/acsami.9b19644},
  doi          = {10.1021/acsami.9b19644},
  volume       = {12},
  year         = {2020},
}