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Lipid-based nanocarriers as a strategy to improve delivery and enhance the efficacy of anti-infective compounds
Secondary Supervisor(s): Dr Tim Overton
University of Registration: University of Birmingham
BBSRC Research Themes:
Project Outline
Antimicrobial resistance (AMR) constitutes a major threat to public health. Bacteria employ numerous strategies to resist antibiotic action, including forming a glue-like protective matrix called biofilm, and expelling antibiotic from cell interiors using efflux pumps.[1] Efflux pump inhibitors (EPIs) offer a promising strategy to combat AMR; however, issues such as poor compound solubility and host toxicity present a major stumbling block to their widespread use.[2] Nanosized lipid bilayer particles, called liposomes, as well as lipid-coated nanoparticles, offer a solution to such delivery difficulties. These multi-compartment structures can (co-)encapsulate and effectively deliver a range of anti-infective compounds to their bacterial target sites.[3]
This project will explore the ability of lipid-based nanocarriers to improve EPI delivery and efficacy in a range of different bacterial species (free-floating and biofilm form). The potential for synergy resulting from nanocarrier-mediated combination delivery of an EPI together with a second anti-infective compound will also be investigated.
Lipid-based nanocarriers loaded with EPI will be produced using techniques such as microfluidic mixing and characterised by dynamic light scattering and high-performance liquid chromatography. Microbiological testing of loaded nanocarriers will include minimum inhibitory concentration testing of antibacterial efficacy, flow cytometry, and use of advanced microscopic imaging modalities to visualise nanocarrier-bacteria interactions.
The interdisciplinary project will be supervised by Dr Sarah Gordon (Pharmacy), an experienced formulation scientist in the use of lipid-based nanocarriers for anti-infective delivery, and Dr Tim Overton (Chemical Engineering), an expert on microbial physiology and antimicrobial resistance.
[1] Whittle et al., mBio 2024, 15: e0237024
[2] Duffey et al., ACS Infect Dis 2024, 10:1458-1482
[3] Menina et al., Adv Healthc Mater 2019, 8: e1900564