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Characterization of Membrane Transporters by Heterologous Expression in E. coli and Production of Membrane Vesicles
Published on: December 31, 2019
Ammonia uptake by transmembrane pH gradient poly(isoprene)-block-poly(ethylene glycol) polymersomes
Aaron C Schmidt1, Erik R Hebels1, Charlotte Weitzel1
1Institute of Pharmaceutical Sciences, Department of Chemistry and Applied Biosciences, ETH Zurich, 8093 Zurich, Switzerland. jleroux@ethz.ch.
Polymer-based polymersomes show promise for treating hyperammonemia by capturing excess ammonia. Crosslinking enhanced their stability and ammonia uptake in simulated colon conditions, suggesting potential for chronic oral therapy.
Area of Science:
- Biomaterials Science
- Nanotechnology
- Drug Delivery
Background:
- Hyperammonemia, caused by urea cycle disorders or liver disease, leads to toxic ammonia accumulation and neurodegeneration.
- Current treatments for hyperammonemia are limited, necessitating novel therapeutic strategies.
Purpose of the Study:
- To investigate poly(isoprene)-block-poly(ethylene glycol) (PI-b-PEG) polymersomes for ammonia detoxification.
- To assess the impact of polymer structure and crosslinking on polymersome stability and ammonia sequestration capacity.
Main Methods:
- Synthesis of PI-b-PEG polymers via nitroxide-mediated polymerization.
- Screening of polymers for self-assembly into polymersomes in aqueous media.
- In vitro investigation of ammonia sequestration in simulated intestinal and colonic fluids.
Main Results:
- Polymersomes effectively sequestered ammonia in simulated intestinal fluids.
- Ammonia uptake was significantly reduced in simulated colonic conditions due to dehydration.
- Polymeric crosslinking of the PI block enhanced polymersome stability and partially restored ammonia capture in the simulated colon.
Conclusions:
- PI-b-PEG polymersomes demonstrate potential for ammonia detoxification.
- Enhanced stability through crosslinking improves efficacy in challenging physiological environments.
- These findings support the development of stable polymersomes for chronic oral treatment of hyperammonemia.
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