An Investigation of PS‐b‐PEO Polymersomes for the Oral Treatment and Diagnosis of Hyperammonemia. Issue 50 (13th November 2019)

• Record Type: Journal Article
• Authors: Matoori, Simon; Bao, Yinyin; Schmidt, Aaron; Fischer, Eric J.; Ochoa‐Sanchez, Rafael; Tremblay, Mélanie; Oliveira, Mariana M.; Rose, Christopher F.; Leroux, Jean‐Christophe
• Is Part Of: Small. Volume 15:Issue 50(2019)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2019-11-13
• Subjects: ammonia -- hyperammonemia -- oral delivery -- poly(styrene)‐b‐poly(ethylene oxide) -- polymersomes; Nanotechnology -- Periodicals; Nanoparticles -- Periodicals; Microtechnology -- Periodicals; 620.5
• DOI: 10.1002/smll.201902347
• Languages: English
• ISSNs: 1613-6810

Abstract

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. Abstract : Transmembrane pH‐gradient polymersomes made of poly(styrene)‐ b ‐poly(ethylene oxide) are investigated as an oral treatment of hyperammonemia, a complication in patients with liver disease, and as an assay to quantify ammonia in biological fluids. These vesicles efficiently and selectively sequester ammonia under extreme conditions but do not lower plasmatic ammonia in hyperammonemic rats. They however perform well as ammonia sensors.