UCL Discovery
UCL home » Library Services » Electronic resources » UCL Discovery

Novel Antibiotic-Loaded Particles Conferring Eradication of Deep Tissue Bacterial Reservoirs for the Treatment of Chronic Urinary Tract Infection

Lau, W; Rohn, J; Dharmasena, D; Horsley, H; Jafari, N; Malone-Lee, J; Stride, E; (2020) Novel Antibiotic-Loaded Particles Conferring Eradication of Deep Tissue Bacterial Reservoirs for the Treatment of Chronic Urinary Tract Infection. Journal of Controlled Release 10.1016/j.jconrel.2020.08.048. (In press).

[img] Text
CapFuran JCR Accepted Manuscript.pdf - Accepted version
Access restricted to UCL open access staff until 2 September 2021.

Download (2MB)

Abstract

A significant proportion of urinary tract infection (UTI) patients experience recurrent episodes, due to deep tissue infection and treatment-resistant bacterial reservoirs. Direct bladder instillation of antibiotics has proved disappointing in treating UTI, likely due to the failure of infused antibiotics to penetrate the bladder epithelium and accumulate to high enough levels to kill intracellular bacteria. This work investigates the use of nitrofurantoin loaded poly(lactic-co-glycolic acid) (PLGA) particles to improve delivery to intracellular targets for the treatment of chronic UTI. Using electrohydrodynamic atomisation, we produced particles with an average diameter of 2.8 μm. In broth culture experiments, the biodegradable particles were effective against a number of UTI-relevant bacterial strains. Dye-loaded particles demonstrated that intracellular delivery was achieved in all cells in 2D cultures of a human bladder epithelial progenitor cell line in a dose-dependent manner, achieving far higher efficiency and concentration than equivalent quantities of free drug. Time-lapse video microscopy confirmed that delivery occurred within 30 min of administration, to 100% of cells. Moreover, the particles were able to deliver the drug to cells through multiple layers of a 3D human bladder organoid model causing minimal cell toxicity, displaying superior killing of bacterial reservoirs harboured within bladder cells compared with unencapsulated drug. The particles were also able to kill bacterial biofilms more effectively than the free drug. These results illustrate the potential for using antibiotic-loaded microparticles to effectively treat chronic UTIs. Such a delivery method could be extrapolated to other clinical indications where robust intracellular delivery is required, such as oncology and gene therapy.

Type: Article
Title: Novel Antibiotic-Loaded Particles Conferring Eradication of Deep Tissue Bacterial Reservoirs for the Treatment of Chronic Urinary Tract Infection
DOI: 10.1016/j.jconrel.2020.08.048
Publisher version: https://doi.org/10.1016/j.jconrel.2020.08.048
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
Keywords: Electrospray, Urinary tract infection, 3D organoid, Intracellular drug delivery, Antimicrobial resistance
UCL classification: UCL
UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine > Renal Medicine
UCL > Provost and Vice Provost Offices > UCL BEAMS
UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Engineering Science
UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Engineering Science > Dept of Mechanical Engineering
URI: https://discovery.ucl.ac.uk/id/eprint/10109140
Downloads since deposit
2Downloads
Download activity - last month
Download activity - last 12 months
Downloads by country - last 12 months

Archive Staff Only

View Item View Item