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An Investigation of PS‐ b ‐PEO Polymersomes for the Oral Treatment and Diagnosis of Hyperammonemia
Author(s) -
Matoori Simon,
Bao Yinyin,
Schmidt Aaron,
Fischer Eric J.,
OchoaSanchez Rafael,
Tremblay Mélanie,
Oliveira Mariana M.,
Rose Christopher F.,
Leroux JeanChristophe
Publication year - 2019
Publication title -
small
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.785
H-Index - 236
eISSN - 1613-6829
pISSN - 1613-6810
DOI - 10.1002/smll.201902347
Subject(s) - polymersome , hyperammonemia , chemistry , ethylene glycol , urea cycle , vesicle , chromatography , pharmacology , biochemistry , amphiphile , medicine , arginine , copolymer , organic chemistry , membrane , amino acid , polymer
Abstract Ammonia‐scavenging transmembrane pH‐gradient poly(styrene)‐ b ‐poly(ethylene oxide) polymersomes are 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 are highly stable in simulated intestinal fluids at extreme bile salt and osmolality conditions, they unexpectedly do not reduce plasmatic ammonia levels in cirrhotic rats after oral dosing. Incubation in dietary fiber hydrogels mimicking the colonic environment suggests that the vesicles are probably destabilized during the dehydration of the intestinal chyme. The 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 polymersome‐based assay could prove useful in the monitoring of hyperammonemic patients and in other applications such as drug screening tests.