Preliminary studies on validation of calu-3 cell line as a model for screening respiratory mucosa irritation and toxicity

There is need to develop reproducible methods and experimental models for screening mucosal irritation and toxicity for drugs and pharmaceutical excipients. The aim of this study was to validate Calu-3 cell line as a model for screening respiratory irritation and toxicity of drugs and excipients. Ei...

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Published in:Pharmaceutics 2014-06, Vol.6 (2), p.268-280
Main Authors: Ihekwereme, Chibueze, Esimone, Charles, Shao, Di, Agu, Remigius U
Format: Article
Language:English
Subjects:
Calu-3 cells
Drug therapy
MTT
mucosal toxicity
Mucous membrane
Toxicity
toxicity prediction
Validation studies
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cited_by cdi_FETCH-LOGICAL-c4178-994fadaddec7765aa7049bc5602373dbce01d397ea00f2683aa2c47692bebe03
cites cdi_FETCH-LOGICAL-c4178-994fadaddec7765aa7049bc5602373dbce01d397ea00f2683aa2c47692bebe03
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container_title Pharmaceutics
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creator Ihekwereme, Chibueze
Esimone, Charles
Shao, Di
Agu, Remigius U
description There is need to develop reproducible methods and experimental models for screening mucosal irritation and toxicity for drugs and pharmaceutical excipients. The aim of this study was to validate Calu-3 cell line as a model for screening respiratory irritation and toxicity of drugs and excipients. Eighteen test compounds were selected according to their irritation potential and European Centre for the Validation of Alternative Methods (ECVAM) guidelines. Cell toxicity and irritation was determined using MTT assay. Data analysis and interpretation were done using modified ECVAM approach; where replicate values met acceptance criteria if percent relative standard deviation (RSD) of the raw data is
doi_str_mv 10.3390/pharmaceutics6020268
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The aim of this study was to validate Calu-3 cell line as a model for screening respiratory irritation and toxicity of drugs and excipients. Eighteen test compounds were selected according to their irritation potential and European Centre for the Validation of Alternative Methods (ECVAM) guidelines. Cell toxicity and irritation was determined using MTT assay. Data analysis and interpretation were done using modified ECVAM approach; where replicate values met acceptance criteria if percent relative standard deviation (RSD) of the raw data is &lt;18%. Compounds with mean relative viability values of 50% and below were classified as irritant (I); those above 50% were non-irritant (NI). At low concentration (0.2% w/v) and 1 h incubation, the Calu-3 cell culture model accurately predicted the toxicity of most test compounds. The specificity of our proposed model (percentage of in vivo non-irritants correctly predicted), concordance (percentage of compounds correctly predicted) and sensitivity (percentage of in vivo irritants correctly predicted) at 0.2% w/v and 60 min exposure were 100%, 72%, and 44%, respectively. In conclusion, the Calu-3 cell line in conjunction with MTT assay appears to be a potentially useful tool for screening drugs and excipients for respiratory mucosa irritation and toxicity. 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source Open Access: PubMed Central; Publicly Available Content (ProQuest); IngentaConnect Journals
subjects Calu-3 cells
Drug therapy
MTT
mucosal toxicity
Mucous membrane
Toxicity
toxicity prediction
Validation studies
title Preliminary studies on validation of calu-3 cell line as a model for screening respiratory mucosa irritation and toxicity
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