Colloidal systems (e.g. liposomes) have been investigated for the treatment of intoxications to xenobiotics such as overdosed drugs, as well as certain metabolites whose levels can reach toxic concentrations in diseased states. When injected intravenously or intraperitoneally, it was for example demonstrated that liposomes bearing a transmembrane pH gradient were particularly effective for sequestering weakly basic drugs and metabolites. However, under certain circumstances, liposomes suffer from instability issues. The aim of this work was to identify highly stable polymer-based vesicles (i.e. polymersomes) which would be suitable for sequestering weakly basic toxic compounds when administered in a non-parenteral fashion (e.g. oral or topical). To this purpose, a small library of poly(isoprene)-b-poly(ethylene oxide) (PI-b-PEOx; x: 750, 2000, 5000 Da) was synthesized employing nitroxide-mediated polymerization (NMP), targeting different hydrophobic/hydrophilic mass ratios (1 up to 6). In a next step, the polymers’ self-assembling behavior was investigated, employing both solvent-switch and emulsification methods. About half of the polymers showed vesicular morphologies in the micrometer range, and were able to trap and retain the model dye pyranine. Amongst these formulations, PI-b-PEO prepared by the emulsification method in dichloromethane, exhibited good stability and retention properties, and was therefore tested in vitro under various conditions for its ability to trap ammonia, a model toxic metabolite. The selected polymers showed capture capacities in the range of liposomal formulations, which have been previously reported for the treatment of hyperammonemia by peritoneal dialysis. They showed high stability in bile salt containing medium, making them an ideal candidate to sequester excess ammonia produced in the colon. In a next step, these polymersomes will be evaluated for the sequestration of trimethylamine, a methylated analogue of ammonia, which in excess is associated to a rare disease known as trimethylaminuria.

Polymersomes for biodetoxification applications

2019 Fall National Meeting

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