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Exploring Light-Sensitive Nanocarriers for Simultaneous Triggered Antibiotic Release and Disruption of Biofilms Upon Generation of Laser-Induced Vapor Nanobubbles

Authors
  • Teirlinck, Eline1, 2
  • Barras, Alexandre3
  • Liu, Jing1, 2
  • Fraire, Juan C.1, 2
  • Lajunen, Tatu4
  • Xiong, Ranhua1, 2
  • Forier, Katrien1, 2
  • Li, Chengnan3
  • Urtti, Arto4, 5, 6
  • Boukherroub, Rabah3
  • Szunerits, Sabine3
  • De Smedt, Stefaan C.1, 2
  • Coenye, Tom
  • Braeckmans, Kevin1, 2, 3
  • 1 (S.C.D.S.)
  • 2 Centre for Nano- and Biophotonics, 9000 Ghent, Belgium
  • 3 (S.S.)
  • 4 (A.U.)
  • 5 School of Pharmacy, University of Eastern Finland, Yliopistonranta 1, 70211 Kuopio, Finland
  • 6 Laboratory of Biohybrid Technologies, Institute of Chemistry, St. Petersburg State University, Universitetskii pr. 26, Peterhoff, St. 198504 Petersburg, Russia
Type
Published Article
Journal
Pharmaceutics
Publisher
MDPI
Publication Date
May 01, 2019
Volume
11
Issue
5
Identifiers
DOI: 10.3390/pharmaceutics11050201
PMID: 31052369
PMCID: PMC6571820
Source
PubMed Central
Keywords
License
Green

Abstract

Impaired penetration of antibiotics through bacterial biofilms is one of the reasons for failure of antimicrobial therapy. Hindered drug diffusion is caused on the one hand by interactions with the sticky biofilm matrix and on the other hand by the fact that bacterial cells are organized in densely packed clusters of cells. Binding interactions with the biofilm matrix can be avoided by encapsulating the antibiotics into nanocarriers, while interfering with the integrity of the dense cell clusters can enhance drug transport deep into the biofilm. Vapor nanobubbles (VNB), generated from laser irradiated nanoparticles, are a recently reported effective way to loosen up the biofilm structure in order to enhance drug transport and efficacy. In the present study, we explored if the disruptive force of VNB can be used simultaneously to interfere with the biofilm structure and trigger antibiotic release from light-responsive nanocarriers. The antibiotic tobramycin was incorporated in two types of light-responsive nanocarriers—liposomes functionalized with gold nanoparticles (Lip-AuNP) and graphene quantum dots (GQD)—and their efficacy was evaluated on Pseudomonas aeruginosa biofilms. Even though the anti-biofilm efficacy of tobramycin was improved by liposomal encapsulation, electrostatic functionalization with 70 nm AuNP unfortunately resulted in premature leakage of tobramycin in a matter of hours. Laser-irradiation consequently did not further improve P. aeruginosa biofilm eradication. Adsorption of tobramycin to GQD, on the other hand, did result in a stable formulation with high encapsulation efficiency, without burst release of tobramycin from the nanocarriers. However, even though laser-induced VNB formation from GQD resulted in biofilm disruption, an enhanced anti-biofilm effect was not achieved due to tobramycin not being efficiently released from GQD. Even though this study was unsuccessful in designing suitable nanocarriers for simultaneous biofilm disruption and light-triggered release of tobramycin, it provides insights into the difficulties and challenges that need to be considered for future developments in this regard.

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