RT Journal Article SR Electronic T1 An investigation of PS-b-PEO polymersomes for the oral treatment and diagnosis of hyperammonemia JF bioRxiv FD Cold Spring Harbor Laboratory SP 631630 DO 10.1101/631630 A1 Simon Matoori A1 Yinyin Bao A1 Aaron Schmidt A1 Eric J. Fischer A1 Rafael Ochoa-Sanchez A1 Mélanie Tremblay A1 Mariana Oliveira A1 Christopher F. Rose A1 Jean-Christophe Leroux YR 2019 UL http://biorxiv.org/content/early/2019/05/08/631630.abstract AB Ammonia-scavenging transmembrane pH-gradient poly(styrene)-b-poly(ethylene oxide) polymersomes were investigated for the oral treatment and diagnosis of hyperammonemia, a condition associated with serious neurologic complications in patients with liver disease as well as in infants with urea cycle disorders. While these polymersomes were highly stable in simulated intestinal fluids at extreme bile salt and osmolality conditions, they unexpectedly did not reduce plasmatic ammonia levels in cirrhotic rats after oral dosing. Incubation in dietary fiber hydrogels mimicking the colonic environment suggested that the vesicles were probably destabilized during the dehydration of the intestinal chyme. Our findings question the relevance of commonly used simulated intestinal fluids for studying vesicular stability. With the encapsulation of a pH-sensitive dye in the polymersome core, the local pH increase upon ammonia influx could be exploited to assess the ammonia concentration in the plasma of healthy and cirrhotic rats as well as in other fluids. Due to its high sensitivity and selectivity, this novel polymersome-based assay could prove useful in the monitoring of hyperammonemic patients and in other applications such as drug screening tests.