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Antibiotic-Loaded Polymersomes for Clearance of Intracellular Burkholderia thailandensis
Eleanor Porges1,2,3,4, Dominic Jenner5, Adam W Taylor5,6
1Bioengineering Sciences Group, Faculty of Engineering and the Environment, University of Southampton, Highfield, Southampton SO17 1BJ, United Kingdom.
Abstract:
Melioidosis caused by the facultative intracellular pathogen Burkholderia pseudomallei is difficult to treat due to poor intracellular bioavailability of antibiotics and antibiotic resistance. In the absence of novel compounds, polymersome (PM) encapsulation may increase the efficacy of existing antibiotics and reduce antibiotic resistance by promoting targeted, infection-specific intracellular uptake. In this study, we developed PMs composed of widely available poly(ethylene oxide)-polycaprolactone block copolymers and demonstrated their delivery to intracellular B. thailandensis infection using multispectral imaging flow cytometry (IFC) and coherent anti-Stokes Raman scattering microscopy. Antibiotics were tightly sequestered in PMs and did not inhibit the growth of free-living B. thailandensis. However, on uptake of antibiotic-loaded PMs by infected macrophages, IFC demonstrated PM colocalization with intracellular B. thailandensis and a significant inhibition of their growth. We conclude that PMs are a viable approach for the targeted antibiotic treatment of persistent intracellular Burkholderia infection.
Insights
Polymersomes (PMs) effectively deliver antibiotics inside infected cells, overcoming antibiotic resistance in Burkholderia infections. This targeted approach enhances treatment efficacy for persistent intracellular bacterial infections.
Area of Science:
- Nanotechnology in Drug Delivery
- Infectious Diseases
- Microbiology
Background:
- Melioidosis, caused by Burkholderia pseudomallei, presents treatment challenges due to poor antibiotic penetration into infected cells and emerging antibiotic resistance.
- Existing antibiotics struggle with intracellular bioavailability, limiting their effectiveness against persistent intracellular Burkholderia infections.
Purpose of the Study:
- To develop and evaluate polymersomes (PMs) for enhanced intracellular delivery of antibiotics to combat Burkholderia infections.
- To investigate if PM encapsulation can improve antibiotic efficacy and reduce resistance in treating intracellular bacterial pathogens.
Main Methods:
- Developed poly(ethylene oxide)-polycaprolactone block copolymer-based polymersomes (PMs).
- Utilized multispectral imaging flow cytometry (IFC) and coherent anti-Stokes Raman scattering microscopy to track PM delivery to intracellular Burkholderia thailandensis.
- Assessed the impact of antibiotic-loaded PMs on intracellular bacterial growth within infected macrophages.
Main Results:
- Polymersomes successfully delivered encapsulated antibiotics to intracellular Burkholderia thailandensis infections in macrophages.
- IFC confirmed colocalization of PMs with intracellular bacteria, demonstrating targeted delivery.
- Uptake of antibiotic-loaded PMs resulted in significant inhibition of intracellular bacterial growth, unlike free antibiotics.
Conclusions:
- Polymersomes are a promising strategy for targeted antibiotic delivery against persistent intracellular Burkholderia infections.
- This approach enhances antibiotic efficacy and offers a potential solution to overcome antibiotic resistance in treating such infections.
