Preclinical evaluation of liposome-supported peritoneal dialysis for the treatment of hyperammonemic crises

Matoori, Simon; Forster, Vincent; Agostoni, Valentina; Bettschart‐Wolfensberger, Regula; Bektas, Rima N; Thöny, Beat; Häberle, Johannes; Leroux, Jean‐Christophe; Kabbaj, Meriam

doi:10.1016/j.jconrel.2020.08.040

Cited by 13 publications

(16 citation statements)

References 37 publications

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“…In addition, there were no complement-activation-related pseudoallergy reactions and the LSPD was tolerated well. Finally, in a hyperammonaemic pig model, pH-gradient liposome-containing dialysate was found to have significantly higher levels of ammonia in the peritoneal fluid when compared with the liposome-free control group [16]. Given that hyperammonemia carries a poor prognosis in liver failure, with the risk of encephalopathy, coma and death, and that there are limited treatment strategies available, LSPD represents a promising treatment avenue.…”

Section: Endogenous Toxic Substancesmentioning

confidence: 95%

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Liposomes to Augment Dialysis in Preclinical Models: A Structured Review

et al. 2021

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In recent years, a number of groups have been investigating the use of “empty” liposomes with no drug loaded as scavengers both for exogenous intoxicants and endogenous toxic molecules. Preclinical trials have demonstrated that repurposing liposomes to sequester such compounds may prove clinically useful. The use of such “empty” liposomes in the dialysate during dialysis avoids recognition by complement surveillance, allowing high doses of liposomes to be used. The “reach” of dialysis may also be increased to molecules that are not traditionally dialysable. We aim to review the current literature in this area with the aims of increasing awareness and informing further research. A structured literature search identified thirteen papers which met the inclusion criteria. Augmenting the extraction of ammonia in hepatic failure with pH-gradient liposomes with acidic centres in peritoneal dialysis is the most studied area, with work progressing toward phase one trials. Liposomes used to augment the removal of exogenous intoxicants and protein-bound uraemic and hepatic toxins that accumulate in these organ failures and liposome-supported enzymatic dialysis have also been studied. It is conceivable that liposomes will be repurposed from the role of pharmaceutical vectors to gain further indications as clinically useful nanomedical antidotes/treatments within the next decade.

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Section: Endogenous Toxic Substancesmentioning

confidence: 95%

“…Matoori et al investigated the pharmacokinetics and safety profile of LSPD using pH-gradient liposomes with acidic centres in dialysate in healthy minipigs [16]. This study was undertaken with a view toward meeting safety requirements for approval for a first-in-human study.…”

Section: Endogenous Toxic Substancesmentioning

confidence: 99%

Liposomes to Augment Dialysis in Preclinical Models: A Structured Review

et al. 2021

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“…39 In a large animal study in minipigs, these intraperitoneally administered liposomes took up large amounts of ammonia, did not accumulate in the peritoneal space even after repeated administration, and showed a favorable toxicity profile. 44 In a phase Ib clinical study in acute-on-chronic liver disease patients, liposomal peritoneal dialysis was well tolerated, had a high and dose-dependent ammonia clearance, and showed promising improvements in hepatic encephalopathy based on psychometric tests. 45 To develop the ammonia assay, we aimed to use ammonia-sequestering transmembrane pH gradient vesicles and to base the mechanism of action on the luminal pH increase that occurs when ammonia is protonated in the vesicular core.…”

Section: T H Imentioning

confidence: 99%

Vesicular Diagnostics: A Spotlight on Lactate- and Ammonia-Sensing Systems

Matoori

2023

ACS Appl. Bio Mater.

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Liposomes are a highly successful drug delivery system with over 15 FDA-approved formulations. Beyond delivering drugs, lipid and polymer vesicles have successfully been used for diagnostic applications. These applications range from more traditional uses, such as releasing diagnostic agents in a controlled manner, to leveraging the unique membrane properties to separate analytes and provide isolated reaction compartments in complex biological matrices. In this Spotlight on Applications, I highlight the complexities in the development and translation of diagnostic vesicles with two case studies, a liposomal reaction compartment for lactate sensing and a transmembrane pH-gradient polymersome for ammonia sensing.

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“…These vesicles were made of synthetic lipids and contained quenched carboxyfluorescein, which became fluorescent after lysis by cytotoxins secreted by biofilm-forming pathogenic bacteria S. aureus, P. aeruginosa , and Enterococcus faecalis in an ex vivo porcine burn wound model . While these systems were shown to work well, vesicles loaded with hydrophilic cargo are often leaky in solution and may break during drying procedures; this issue often limits shelf life. − A polyurethane dressing loaded with a lipase-sensitive pro-drug sensed bacterial lipase activity . The chromogenic probe contained a lipase-sensitive ester bond which releases the dye hemicyanine after enzymatic cleavage and turns the dressing from yellow to green to red.…”

Section: Diagnostic Wound Dressings Under Preclinical Investigationmentioning

confidence: 99%

Next-Generation Diagnostic Wound Dressings for Diabetic Wounds

Stupnitskaia

Matoori

2022

ACS Meas. Sci. Au

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Chronic lower extremity wounds (diabetic foot ulcers) are a serious and prevalent complication of diabetes. These wounds exhibit low healing rates and present a high risk of amputation. Current diagnostic options for foot ulcers are limited to macroscopic wound analysis such as wound depth, implicated tissues, and infection. Molecular diagnostics promises to improve foot ulcer diagnosis, staging, and assessment of the treatment response. In this perspective, we report recent progress in understanding the pathophysiology of diabetic wound healing and point to recently emerged novel molecular targets for wound diagnostics. We discuss selected diagnostic wound dressings under preclinical development that detect one or several inflammatory markers, bacterial secretions, hyperglycemia, and mechanical stress. We also highlight key translational challenges of investigational diagnostic bandages for diabetic foot ulcers.

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Preclinical evaluation of liposome-supported peritoneal dialysis for the treatment of hyperammonemic crises

Cited by 13 publications

References 37 publications

Liposomes to Augment Dialysis in Preclinical Models: A Structured Review

Liposomes to Augment Dialysis in Preclinical Models: A Structured Review

Vesicular Diagnostics: A Spotlight on Lactate- and Ammonia-Sensing Systems

Next-Generation Diagnostic Wound Dressings for Diabetic Wounds

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