Liposome-supported peritoneal dialysis in the treatment of severe hyperammonemia: An investigation on potential interactions

Giacalone, Giovanna; Matoori, Simon; Agostoni, Valentina; Forster, Vincent; Kabbaj, Meriam; Eggenschwiler, Sarah; Lussi, Martin; Gottardi, Andrea De; Zamboni, Nicola; Leroux, Jean‐Christophe

doi:10.1016/j.jconrel.2018.03.030

Cited by 19 publications

(26 citation statements)

References 41 publications

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“…VS-01 simultaneously removes urea and toxins that accumulate in these patients, by promoting their passive diffusion into the liposomes' supporting fluid. 165 At the end of the treatment, the fluid containing ammonialoaded liposomes is withdrawn from the peritoneal cavity by gravity, in the same way ascitic fluid is drained by paracentesis.…”

Section: Postbioticsmentioning

confidence: 99%

“…oedema. 165 Additionally, untargeted metabolomic studies revealed that the vast majority of toxins known to be present in excess in patients with liver dysfunction were removed by VS-01 concomitantly with ammonia. Hence, VS-01 can provide prompt detoxification and thereby support the 3 primary organs (brain, liver and kidney) that can fail in advanced cirrhosis.…”

Section: Postbioticsmentioning

confidence: 99%

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The gut-liver axis in liver disease: Pathophysiological basis for therapy

Albillos

Gottardi

Rescigno

2020

Journal of Hepatology

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1,192

881

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The gut-liver axis refers to the bidirectional relationship between the gut and its microbiota, and the liver, resulting from the integration of signals generated by dietary, genetic and environmental factors. This reciprocal interaction is established by the portal vein which enables transport of gut-derived products directly to the liver, and the liver feedback route of bile and antibody secretion to the intestine. The intestinal mucosal and vascular barrier is the functional and anatomical structure that serves as a playground for the interactions between the gut and the liver, limiting the systemic dissemination of microbes and toxins while allowing nutrients to access the circulation and to reach the liver. The control of microbial communities is critical to maintaining homeostasis of the gut-liver axis, and as part of this bidirectional communication the liver shapes intestinal microbial communities. Alcohol disrupts the gut-liver axis at multiple interconnected levels, including the gut microbiome, mucus barrier, epithelial barrier and at the level of antimicrobial peptide production, which increases microbial exposure and the proinflammatory environment of the liver. Growing evidence indicates the pathogenetic role of microbe-derived metabolites, such as trimethylamine, secondary bile acids, short-chain fatty acids and ethanol, in the pathogenesis of non-alcoholic fatty liver disease. Cirrhosis by itself is associated with profound alterations in gut microbiota and damage at the different levels of defence of the intestinal barrier, including the epithelial, vascular and immune barriers. The relevance of the severe disturbance of the intestinal barrier in cirrhosis has been linked to translocation of live bacteria, bacterial infections and disease progression. The identification of the elements of the gut-liver axis primarily damaged in each chronic liver disease offers possibilities for intervention. Beyond antibiotics, upcoming therapies centred on the gut include new generations of probiotics, bacterial metabolites (postbiotics), faecal microbial transplantation, and carbon nanoparticles. FXR-agonists target both the gut and the liver and are currently being tested in different liver diseases. Finally, synthetic biotic medicines, phages that target specific bacteria or therapies that create physical barriers between the gut and the liver offer new therapeutic approaches.

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Section: Postbioticsmentioning

confidence: 99%

Section: Postbioticsmentioning

confidence: 99%

The gut-liver axis in liver disease: Pathophysiological basis for therapy

Albillos

Gottardi

Rescigno

2020

Journal of Hepatology

Self Cite

1,192

881

View full text Add to dashboard Cite

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“…37 The weak base ammonia can be efficiently and selectively captured by transmembrane pH-gradient vesicles with an acidic core. 37,48,146,147,161 While neither cholesterolcontaining PEGylated DPPC and DSPC liposomes nor PBD-b-PEO polymersomes were resistant to physiologically relevant bile salt concentrations, PS-b-PEO polymersomes preserved their ammonia capture capacity in bile salt-containing media at extreme osmolarity levels and in digestive enzyme-containing fluids. 37 Despite performing well in commonly used GI-simulating fluids, these polymersomes proved to be unstable in dietary fiber-based hydrogels and failed to decrease plasma ammonia levels in hyperammonemic rats.…”

Section: Oral Administrationmentioning

confidence: 99%

“…37 In contrast, the permeability of cholesterol-containing PEGylated DPPC liposomes towards weakly basic drugs was higher. 147 The reversibly glucose-sequestering PEO-b-poly(CMA-stat-DEA-stat-GEMA) glycopolymersomes described above were further used as a glucose assay. 127 As they swelled from 400 to 800 nm upon exposition to glucose solutions (''glucose sponge''), the authors proposed a particle size-based glucose-sensing system.…”

Section: Polymersomes As Reaction Compartmentsmentioning

confidence: 99%

Twenty-five years of polymersomes: lost in translation?

2020

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“…The underlying principle is the rapid diffusion of the nonprotonated amine species across the membrane and its subsequent protonation inside an acidic core, trapping it within the vesicle lumen. Our group has previously shown that liposomal carriers bearing a pH gradient could efficiently [ 17 ] and in a relatively selective fashion [ 18 ] capture the smaller metabolite ammonia in the peritoneal space. This system lowered systemic ammonia and brain edema when applied via peritoneal dialysis in bile‐duct ligated rats, a model of hyperammonemia.…”

Section: Figurementioning

confidence: 99%

Engineered Polymersomes for the Treatment of Fish Odor Syndrome: A First Randomized Double Blind Olfactory Study

et al. 2020

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Trimethylamine (TMA) is a metabolite overtly present in patients suffering from trimethylaminuria (TMAU), a rare genetic disorder characterized by a strong “fishy” body odor. To date, no approved pharmacological treatment to sequester excess TMA on the skin of patients exists. Here, transmembrane pH gradient poly(isoprene)‐block‐poly(ethylene glycol) (PI‐b‐PEG) polymersomes are investigated for the topical removal of TMA. PI‐b‐PEG amphiphiles of varying chain length are synthesized and evaluated for their ability to form vesicular structures in aqueous media. The optimization of the PI/PEG ratio of transmembrane pH gradient polymersomes allows for the rapid and efficient capture of TMA both in solution and after incorporation into a topical hydrogel matrix at the pH of the skin. A subsequent double blind olfactory study reveals a significant decrease in perceived odor intensity after application of the polymersome‐based formulation on artificial skin substrates that has been incubated in TMA‐containing medium. This simple and novel approach has the potential to ease the burden of people suffering from TMAU.

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Liposome-supported peritoneal dialysis in the treatment of severe hyperammonemia: An investigation on potential interactions

Cited by 19 publications

References 41 publications

The gut-liver axis in liver disease: Pathophysiological basis for therapy

The gut-liver axis in liver disease: Pathophysiological basis for therapy

Twenty-five years of polymersomes: lost in translation?

Engineered Polymersomes for the Treatment of Fish Odor Syndrome: A First Randomized Double Blind Olfactory Study

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