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Novel Topical Microbicides Through Combinatorial Strategies
PURPOSE: Developing microbicides for topical epithelial applications is extremely challenging, as evidenced by the scarcity of approved products even after decades of research. Chemical enhancers, including surfactants, are known to be effective antimicrobial agents but are typically toxic towards e...
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Formato: | Texto |
Lenguaje: | English |
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Springer US
2010
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2883926/ https://www.ncbi.nlm.nih.gov/pubmed/20306119 http://dx.doi.org/10.1007/s11095-010-0095-9 |
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author | Arora, Anubhav Mitragotri, Samir |
author_facet | Arora, Anubhav Mitragotri, Samir |
author_sort | Arora, Anubhav |
collection | PubMed |
description | PURPOSE: Developing microbicides for topical epithelial applications is extremely challenging, as evidenced by the scarcity of approved products even after decades of research. Chemical enhancers, including surfactants, are known to be effective antimicrobial agents but are typically toxic towards epithelial cells. Here, we report on the discovery of unique surfactant formulations with improved safety and efficacy profile for epithelial applications, via a combination of high throughput screening techniques. METHODS: Over three-hundred formulations derived from nine surfactants were screened for antibacterial properties against E. coli in vitro. A subset of these formulations showed high antibacterial activity and was screened for cytotoxicity in vitro. Formulations showing high antibacterial activity and reduced cytotoxicity compared to their individual components were tested for efficacy against B. thailendensis, a model for melioidosis-causing B. pseudomallei. RESULTS: Lead formulations showed lower toxicity towards epidermal keratinocytes, with LC(50) values up to 3.5-fold higher than their component surfactants, while maintaining antibacterial efficacy against B. thailendensis. CONCLUSIONS: Our results demonstrate that such a combinatorial screening approach can be used for designing safe and potent microbicides for epithelial applications. |
format | Text |
id | pubmed-2883926 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2010 |
publisher | Springer US |
record_format | MEDLINE/PubMed |
spelling | pubmed-28839262010-06-21 Novel Topical Microbicides Through Combinatorial Strategies Arora, Anubhav Mitragotri, Samir Pharm Res Research Paper PURPOSE: Developing microbicides for topical epithelial applications is extremely challenging, as evidenced by the scarcity of approved products even after decades of research. Chemical enhancers, including surfactants, are known to be effective antimicrobial agents but are typically toxic towards epithelial cells. Here, we report on the discovery of unique surfactant formulations with improved safety and efficacy profile for epithelial applications, via a combination of high throughput screening techniques. METHODS: Over three-hundred formulations derived from nine surfactants were screened for antibacterial properties against E. coli in vitro. A subset of these formulations showed high antibacterial activity and was screened for cytotoxicity in vitro. Formulations showing high antibacterial activity and reduced cytotoxicity compared to their individual components were tested for efficacy against B. thailendensis, a model for melioidosis-causing B. pseudomallei. RESULTS: Lead formulations showed lower toxicity towards epidermal keratinocytes, with LC(50) values up to 3.5-fold higher than their component surfactants, while maintaining antibacterial efficacy against B. thailendensis. CONCLUSIONS: Our results demonstrate that such a combinatorial screening approach can be used for designing safe and potent microbicides for epithelial applications. Springer US 2010-03-20 2010 /pmc/articles/PMC2883926/ /pubmed/20306119 http://dx.doi.org/10.1007/s11095-010-0095-9 Text en © The Author(s) 2010 https://creativecommons.org/licenses/by-nc/4.0/ This article is distributed under the terms of the Creative Commons Attribution Noncommercial License which permits any noncommercial use, distribution, and reproduction in any medium, provided the original author(s) and source are credited. |
spellingShingle | Research Paper Arora, Anubhav Mitragotri, Samir Novel Topical Microbicides Through Combinatorial Strategies |
title | Novel Topical Microbicides Through Combinatorial Strategies |
title_full | Novel Topical Microbicides Through Combinatorial Strategies |
title_fullStr | Novel Topical Microbicides Through Combinatorial Strategies |
title_full_unstemmed | Novel Topical Microbicides Through Combinatorial Strategies |
title_short | Novel Topical Microbicides Through Combinatorial Strategies |
title_sort | novel topical microbicides through combinatorial strategies |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2883926/ https://www.ncbi.nlm.nih.gov/pubmed/20306119 http://dx.doi.org/10.1007/s11095-010-0095-9 |
work_keys_str_mv | AT aroraanubhav noveltopicalmicrobicidesthroughcombinatorialstrategies AT mitragotrisamir noveltopicalmicrobicidesthroughcombinatorialstrategies |