Combining Cytotoxicity Assessment and <i>Xenopus laevis</i> Phenotypic Abnormality Assay as a Predictor of Nanomaterial Safety

Al-Yousuf, Karamallah; Webster, Carl A; Wheeler, Grant N.; Bombelli, Francesca Baldelli; Sherwood, Victoria

doi:10.1002/cptx.25

Cited by 3 publications

(3 citation statements)

References 62 publications

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“…X. laevis embryos could be an ideal model organism to be used for screening new drugs and compounds as screening in Xenopus is comparatively high-throughput relative to screening in rodents (Tomlinson et al, 2009). We have previously developed methods to both screen compounds for novel phenotypes and test toxicity (Al-Yousuf et al, 2017;Tomlinson et al, 2012;Tomlinson et al, 2009;Webster et al, 2016;Liu, 2012, Saide et al, 2019). In addition, Xenopus embryos have been used as a toxicity model for drugs in their early stages of drug safety evaluation in the frog teratogenesis assay-Xenopus (or FETAX assay) (Leconte and Mouche, 2013).…”

Section: Discussionmentioning

confidence: 99%

In Vivo Assessment of Drug-Induced Hepatotoxicity Using Xenopus Embryos

Saide

Wheeler

2020

Cold Spring Harb Protoc

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Failure to predict drug-induced toxicity reactions is a major problem contributing to a high attrition rate and tremendous cost in drug development. Drug screening in X. laevis embryos is high-throughput relative to screening in rodents, potentially making them an ideal model organism for this use. Xenopus embryos have been used as a toxicity model in the frog teratogenesis assay-Xenopus (FETAX assay) for the early stages of drug safety evaluation. We have previously developed compound-screening methods using Xenopus embryos and believe they could be used for in vitro druginduced toxicity safety assessment prior to expensive preclinical trials in mammals. Specifically, Xenopus embryos could help predict drug-induced hepatotoxicity and consequently aid lead candidate prioritization. Here we present methods, which we have modified for use on Xenopus embryos, to help measure the potential for a drug to induce liver toxicity. One such method is the release of the liver-specific micro-RNA (miRNA), miR-122, from the liver into the vasculature as a result of hepatocellular damage, which could be due to drug-induced acute liver injury. Paracetamol, a known hepatotoxin at high doses, was a positive control. We have previously shown that some of the phenotypes of mammalian paracetamol overdose are reflected in Xenopus embryos. Consequently, we have also included a method that measures the concentration of free glutathione (GSH), which is an indicator of paracetamol-induced liver injury. These methods can be used as part of a panel of protocols to help predict the hepatoxicity of a drug at an early stage in drug development.

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Section: Discussionmentioning

confidence: 99%

In Vivo Assessment of Drug-Induced Hepatotoxicity Using Xenopus Embryos

Saide

Wheeler

2020

Cold Spring Harb Protoc

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“…The research has been approved by the local ethical review committee according to UK Home Office regulations. Xenopus laevis embryos were obtained as previously described [31].…”

Section: In Vivo Toxicity Studies In Xenopus Laevis Embryo Modelmentioning

confidence: 99%

“…The Xenopus laevis larvae model was used to assess the toxicity of SLN formulations in order to obtain a robust toxicity profile of anionic and cationic SLN. This model has been previously proposed as a suitable high throughput screening model to fill the gap between the in vitro and in vivo mammalian toxicity models [31,47,48].…”

Section: In Vivo Toxicity Of Sln On Xenopus Laevis Embryo Model Assaymentioning

confidence: 99%

Solid lipid nanoparticles for the delivery of anti-microbial oligonucleotides

González-Paredes¹,

Sitia

Ruyra

et al. 2019

European Journal of Pharmaceutics and Biopharmaceutics

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Novel alternatives to antibiotics are urgently needed for the successful treatment of antimicrobial resistant (AMR) infections. Experimental antibacterial oligonucleotide therapeutics, such as transcription factor decoys (TFD), are a promising approach to circumvent AMR. However, the therapeutic potential of TFD is contingent upon the development of carriers that afford efficient DNA protection against nucleases and delivery of DNA to the target infection site. As a carrier for TFD, here we present three prototypes of anionic solid lipid nanoparticles that were coated with either the cationic bolaamphiphile 12-bistetrahydroacridinium or with protamine. Both compounds switched particles zeta potential to positive values, showing efficient complexation with TFD and demonstrable protection from deoxyribonuclease. The effective delivery of TFD into bacteria was confirmed by confocal microscopy while SLN-bacteria interactions were studied by flow cytometry. Antibacterial efficacy was confirmed using a model TFD

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