PMID- 31804792
OWN - NLM
STAT- MEDLINE
DCOM- 20200928
LR  - 20200928
IS  - 1944-8252 (Electronic)
IS  - 1944-8244 (Linking)
VI  - 12
IP  - 1
DP  - 2020 Jan 8
TI  - Ultrasmall TPGS-PLGA Hybrid Nanoparticles for Site-Specific Delivery of 
      Antibiotics into Pseudomonas aeruginosa Biofilms in Lungs.
PG  - 380-389
LID - 10.1021/acsami.9b19644 [doi]
AB  - 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-alpha-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.
FAU - Wan, Feng
AU  - Wan F
AUID- ORCID: 0000-0003-2822-9029
FAU - Bohr, Soren S-R
AU  - Bohr SS
AUID- ORCID: 0000-0002-8107-2465
AD  - Department of Chemistry & Nano-Science Center , University of Copenhagen , 
      Thorvaldsensvej 40 , DK-1871 Frederiksberg C , Denmark.
AD  - Novo Nordisk Foundation Centre for Protein Research, Faculty of Health and 
      Medical Sciences , University of Copenhagen , Blegdamsvej 3B , 2200 Copenhagen , 
      Denmark.
FAU - Klodzinska, Sylvia Natalie
AU  - Klodzinska SN
FAU - Jumaa, Haidar
AU  - Jumaa H
FAU - Huang, Zheng
AU  - Huang Z
FAU - Nylander, Tommy
AU  - Nylander T
AUID- ORCID: 0000-0001-9420-2217
AD  - Department of Physical Chemistry , Lund University , SE-221 00 Lund , Sweden.
FAU - Thygesen, Mikkel Boas
AU  - Thygesen MB
AUID- ORCID: 0000-0002-0158-2802
AD  - Department of Chemistry & Nano-Science Center , University of Copenhagen , 
      Thorvaldsensvej 40 , DK-1871 Frederiksberg C , Denmark.
AD  - Novo Nordisk Foundation Centre for Protein Research, Faculty of Health and 
      Medical Sciences , University of Copenhagen , Blegdamsvej 3B , 2200 Copenhagen , 
      Denmark.
FAU - Sorensen, Kasper Kildegaard
AU  - Sorensen KK
AD  - Department of Chemistry & Nano-Science Center , University of Copenhagen , 
      Thorvaldsensvej 40 , DK-1871 Frederiksberg C , Denmark.
AD  - Novo Nordisk Foundation Centre for Protein Research, Faculty of Health and 
      Medical Sciences , University of Copenhagen , Blegdamsvej 3B , 2200 Copenhagen , 
      Denmark.
FAU - Jensen, Knud Jorgen
AU  - Jensen KJ
AUID- ORCID: 0000-0003-3525-5452
AD  - Department of Chemistry & Nano-Science Center , University of Copenhagen , 
      Thorvaldsensvej 40 , DK-1871 Frederiksberg C , Denmark.
AD  - Novo Nordisk Foundation Centre for Protein Research, Faculty of Health and 
      Medical Sciences , University of Copenhagen , Blegdamsvej 3B , 2200 Copenhagen , 
      Denmark.
FAU - Sternberg, Claus
AU  - Sternberg C
AD  - Department of Biotechnology and Biomedicine , Technical University of Denmark , 
      Building 221, Soltofts Plads , DK-2800 Lyngby , Denmark.
FAU - Hatzakis, Nikos
AU  - Hatzakis N
AUID- ORCID: 0000-0003-4202-0328
AD  - Department of Chemistry & Nano-Science Center , University of Copenhagen , 
      Thorvaldsensvej 40 , DK-1871 Frederiksberg C , Denmark.
AD  - Novo Nordisk Foundation Centre for Protein Research, Faculty of Health and 
      Medical Sciences , University of Copenhagen , Blegdamsvej 3B , 2200 Copenhagen , 
      Denmark.
FAU - Morck Nielsen, Hanne
AU  - Morck Nielsen H
AUID- ORCID: 0000-0002-7285-9100
LA  - eng
PT  - Journal Article
DEP - 20191217
PL  - United States
TA  - ACS Appl Mater Interfaces
JT  - ACS applied materials & interfaces
JID - 101504991
RN  - 0 (Anti-Bacterial Agents)
RN  - 0 (Drug Carriers)
RN  - 26009-03-0 (Polyglycolic Acid)
SB  - IM
MH  - Administration, Inhalation
MH  - Anti-Bacterial Agents/*chemistry/pharmacology
MH  - Biofilms/*drug effects
MH  - Drug Carriers/*administration & dosage/*chemistry
MH  - Microbial Sensitivity Tests
MH  - Nanoparticles/*chemistry
MH  - Polyglycolic Acid/*administration & dosage/*chemistry
MH  - Pseudomonas aeruginosa/*drug effects
OTO - NOTNLM
OT  - Pseudomonas aeruginosa biofilm
OT  - TPGS-PLGA hybrid nanoparticles
OT  - aerosol administration
OT  - bio-nano interaction
OT  - cystic fibrosis
EDAT- 2019/12/06 06:00
MHDA- 2020/09/29 06:00
CRDT- 2019/12/06 06:00
PHST- 2019/12/06 06:00 [pubmed]
PHST- 2020/09/29 06:00 [medline]
PHST- 2019/12/06 06:00 [entrez]
AID - 10.1021/acsami.9b19644 [doi]
PST - ppublish
SO  - ACS Appl Mater Interfaces. 2020 Jan 8;12(1):380-389. doi: 10.1021/acsami.9b19644. 
      Epub 2019 Dec 17.