PMID- 37059243
OWN - NLM
STAT- MEDLINE
DCOM- 20230512
LR  - 20230512
IS  - 1873-3476 (Electronic)
IS  - 0378-5173 (Linking)
VI  - 639
DP  - 2023 May 25
TI  - Liquid crystalline lipid nanoparticles improve the antibacterial activity of 
      tobramycin and vancomycin against intracellular Pseudomonas aeruginosa and 
      Staphylococcus aureus.
PG  - 122927
LID - S0378-5173(23)00347-2 [pii]
LID - 10.1016/j.ijpharm.2023.122927 [doi]
AB  - The intracellular survival of bacteria is a significant challenge in the fight 
      against antimicrobial resistance. Currently available antibiotics suffer from 
      limited penetration across host cell membranes, resulting in suboptimal treatment 
      against the internalised bacteria. Liquid crystalline nanoparticles (LCNP) are 
      gaining significant research interest in promoting the cellular uptake of 
      therapeutics due to their fusogenic properties; however, they have not been 
      reported for targeting intracellular bacteria. Herein, the cellular 
      internalisation of LCNPs in RAW 264.7 macrophages and A549 epithelial cells was 
      investigated and optimized through the incorporation of a cationic lipid, 
      dimethyldioctadecylammonium bromide (DDAB). LCNPs displayed a honeycomb-like 
      structure, while the inclusion of DDAB resulted into an onion-like organisation 
      with larger internal pores. Cationic LCNPs enhanced the cellular uptake in both 
      cells, reaching up to  approximately  90% uptake in cells. Further, LCNPs were encapsulated 
      with tobramycin or vancomycin to improve their activity against intracellular 
      gram-negative, Pseudomonas aeruginosa (P. aeruginosa) and gram-positive, 
      Staphylococcus aureus (S. aureus) bacteria. The enhanced cellular uptake of 
      cationic LCNP resulted in significant reduction of intracellular bacterial load 
      (up to 90% reduction), compared to antibiotic dosed in its free form; with 
      reduced performance observed for epithelial cells infected with S. aureus. 
      Specifically engineered LCNP can re-sensitise antibiotics against both 
      intracellular Gram positive and negative bacteria in diverse cell lines.
CI  - Copyright (c) 2023 The Author(s). Published by Elsevier B.V. All rights reserved.
FAU - Subramaniam, Santhni
AU  - Subramaniam S
AD  - University of South Australia, UniSA Clinical and Health Sciences, SA 5000, 
      Australia.
FAU - Joyce, Paul
AU  - Joyce P
AD  - University of South Australia, UniSA Clinical and Health Sciences, SA 5000, 
      Australia.
FAU - Prestidge, Clive A
AU  - Prestidge CA
AD  - University of South Australia, UniSA Clinical and Health Sciences, SA 5000, 
      Australia. Electronic address: Clive.Prestidge@unisa.edu.au.
LA  - eng
PT  - Journal Article
DEP - 20230412
PL  - Netherlands
TA  - Int J Pharm
JT  - International journal of pharmaceutics
JID - 7804127
RN  - 6Q205EH1VU (Vancomycin)
RN  - VZ8RRZ51VK (Tobramycin)
RN  - 13146-86-6 (didodecyldimethylammonium)
RN  - 0 (Lipid Nanoparticles)
RN  - 0 (Anti-Bacterial Agents)
SB  - IM
MH  - Humans
MH  - Vancomycin
MH  - Tobramycin/pharmacology
MH  - Staphylococcus aureus
MH  - Pseudomonas aeruginosa/metabolism
MH  - Anti-Bacterial Agents/pharmacology/metabolism
MH  - *Nanoparticles/chemistry
MH  - *Staphylococcal Infections
MH  - Bacteria
MH  - Microbial Sensitivity Tests
OTO - NOTNLM
OT  - Epithelial cells
OT  - Intracellular infection
OT  - Liquid crystalline nanoparticles
OT  - Macrophages
OT  - P. aeruginosa
OT  - S. aureus
OT  - Tobramycin
OT  - Vancomycin
COIS- Declaration of Competing Interest The authors declare that they have no known 
      competing financial interests or personal relationships that could have appeared 
      to influence the work reported in this paper.
EDAT- 2023/04/15 06:00
MHDA- 2023/05/12 07:06
CRDT- 2023/04/14 19:26
PHST- 2023/02/23 00:00 [received]
PHST- 2023/03/24 00:00 [revised]
PHST- 2023/04/01 00:00 [accepted]
PHST- 2023/05/12 07:06 [medline]
PHST- 2023/04/15 06:00 [pubmed]
PHST- 2023/04/14 19:26 [entrez]
AID - S0378-5173(23)00347-2 [pii]
AID - 10.1016/j.ijpharm.2023.122927 [doi]
PST - ppublish
SO  - Int J Pharm. 2023 May 25;639:122927. doi: 10.1016/j.ijpharm.2023.122927. Epub 
      2023 Apr 12.