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Open AccessArticle

Preliminary Studies on Validation of Calu-3 Cell Line as a Model for Screening Respiratory Mucosa Irritation and Toxicity

1
Department of Pharmacology and Toxicology, Nnamdi Azikiwe University, Awka 420281, Nigeria
2
Department of Pharmaceutical Microbiology and Biotechnology, Nnamdi Azikiwe University, Awka 420281, Nigeria
3
Biopharmaceutics and Drug Delivery Laboratory, College of Pharmacy, Dalhousie University, Halifax, NS B3H 3J5, Canada
*
Author to whom correspondence should be addressed.
Pharmaceutics 2014, 6(2), 268-280; https://doi.org/10.3390/pharmaceutics6020268
Received: 26 January 2014 / Revised: 29 May 2014 / Accepted: 3 June 2014 / Published: 13 June 2014
(This article belongs to the Special Issue Respiratory and Nasal Drug Delivery)
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 <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. However, as the data reported in this study were solely based on MTT assay, additional studies are needed using other toxicity-/irritation-indicating methods to confirm the observed trend. View Full-Text
Keywords: Calu-3 cells; MTT; toxicity prediction; mucosal toxicity Calu-3 cells; MTT; toxicity prediction; mucosal toxicity
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MDPI and ACS Style

Ihekwereme, C.; Esimone, C.; Shao, D.; Agu, R.U. Preliminary Studies on Validation of Calu-3 Cell Line as a Model for Screening Respiratory Mucosa Irritation and Toxicity. Pharmaceutics 2014, 6, 268-280. https://doi.org/10.3390/pharmaceutics6020268

AMA Style

Ihekwereme C, Esimone C, Shao D, Agu RU. Preliminary Studies on Validation of Calu-3 Cell Line as a Model for Screening Respiratory Mucosa Irritation and Toxicity. Pharmaceutics. 2014; 6(2):268-280. https://doi.org/10.3390/pharmaceutics6020268

Chicago/Turabian Style

Ihekwereme, Chibueze; Esimone, Charles; Shao, Di; Agu, Remigius U. 2014. "Preliminary Studies on Validation of Calu-3 Cell Line as a Model for Screening Respiratory Mucosa Irritation and Toxicity" Pharmaceutics 6, no. 2: 268-280. https://doi.org/10.3390/pharmaceutics6020268

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