Quantitative analysis of microbicide concentrations in fluids, gels and tissues using confocal Raman spectroscopy.

Topical vaginal anti-HIV microbicides are an important focus in female-based strategies to prevent the sexual transmission of HIV. Understanding microbicide pharmacokinetics is essential to development, characterization and implementation of efficacious microbicide drug delivery formulations. Curren...

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Autores principales:	Oranat Chuchuen, Marcus H Henderson, Craig Sykes, Min Sung Kim, Angela D M Kashuba, David F Katz
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/4a8d884fc32a4cb48752e72f8e037c57
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spelling	oai:doaj.org-article:4a8d884fc32a4cb48752e72f8e037c572021-11-18T08:39:44ZQuantitative analysis of microbicide concentrations in fluids, gels and tissues using confocal Raman spectroscopy.1932-620310.1371/journal.pone.0085124https://doaj.org/article/4a8d884fc32a4cb48752e72f8e037c572013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24386455/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203Topical vaginal anti-HIV microbicides are an important focus in female-based strategies to prevent the sexual transmission of HIV. Understanding microbicide pharmacokinetics is essential to development, characterization and implementation of efficacious microbicide drug delivery formulations. Current methods to measure drug concentrations in tissue (e.g., LC-MS/MS, liquid chromatography coupled with tandem mass spectrometry) are highly sensitive, but destructive and complex. This project explored the use of confocal Raman spectroscopy to detect microbicide drugs and to measure their local concentrations in fluids, drug delivery gels, and tissues. We evaluated three candidate microbicide drugs: tenofovir, Dapivirine and IQP-0528. Measurements were performed in freshly excised porcine buccal tissue specimens, gel vehicles and fluids using two Horiba Raman microscopes, one of which is confocal. Characteristic spectral peak calibrations for each drug were obtained using serial dilutions in the three matrices. These specific Raman bands demonstrated strong linear concentration dependences in the matrices and were characterized with respect to their unique vibrational signatures. At least one specific Raman feature was identified for each drug as a marker band for detection in tissue. Sensitivity of detection was evaluated in the three matrices. A specific peak was also identified for tenofovir diphosphate, the anti-HIV bioactive product of tenofovir after phosphorylation in host cells. Z-scans of drug concentrations vs. depth in excised tissue specimens, incubated under layers of tenofovir solution in a Transwell assay, showed decreasing concentration with depth from the surface into the tissue. Time-dependent concentration profiles were obtained from tissue samples incubated in the Transwell assay, for times ranging 30 minutes - 6 hours. Calibrations and measurements from tissue permeation studies for tenofovir showed good correlation with gold standard LC-MS/MS data. These results demonstrate that confocal Raman spectroscopy holds promise as a tool for practical, minimally invasive, label-free measurement of microbicide drug concentrations in fluids, gels and tissues.Oranat ChuchuenMarcus H HendersonCraig SykesMin Sung KimAngela D M KashubaDavid F KatzPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 12, p e85124 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Oranat Chuchuen Marcus H Henderson Craig Sykes Min Sung Kim Angela D M Kashuba David F Katz Quantitative analysis of microbicide concentrations in fluids, gels and tissues using confocal Raman spectroscopy.
description	Topical vaginal anti-HIV microbicides are an important focus in female-based strategies to prevent the sexual transmission of HIV. Understanding microbicide pharmacokinetics is essential to development, characterization and implementation of efficacious microbicide drug delivery formulations. Current methods to measure drug concentrations in tissue (e.g., LC-MS/MS, liquid chromatography coupled with tandem mass spectrometry) are highly sensitive, but destructive and complex. This project explored the use of confocal Raman spectroscopy to detect microbicide drugs and to measure their local concentrations in fluids, drug delivery gels, and tissues. We evaluated three candidate microbicide drugs: tenofovir, Dapivirine and IQP-0528. Measurements were performed in freshly excised porcine buccal tissue specimens, gel vehicles and fluids using two Horiba Raman microscopes, one of which is confocal. Characteristic spectral peak calibrations for each drug were obtained using serial dilutions in the three matrices. These specific Raman bands demonstrated strong linear concentration dependences in the matrices and were characterized with respect to their unique vibrational signatures. At least one specific Raman feature was identified for each drug as a marker band for detection in tissue. Sensitivity of detection was evaluated in the three matrices. A specific peak was also identified for tenofovir diphosphate, the anti-HIV bioactive product of tenofovir after phosphorylation in host cells. Z-scans of drug concentrations vs. depth in excised tissue specimens, incubated under layers of tenofovir solution in a Transwell assay, showed decreasing concentration with depth from the surface into the tissue. Time-dependent concentration profiles were obtained from tissue samples incubated in the Transwell assay, for times ranging 30 minutes - 6 hours. Calibrations and measurements from tissue permeation studies for tenofovir showed good correlation with gold standard LC-MS/MS data. These results demonstrate that confocal Raman spectroscopy holds promise as a tool for practical, minimally invasive, label-free measurement of microbicide drug concentrations in fluids, gels and tissues.
format	article
author	Oranat Chuchuen Marcus H Henderson Craig Sykes Min Sung Kim Angela D M Kashuba David F Katz
author_facet	Oranat Chuchuen Marcus H Henderson Craig Sykes Min Sung Kim Angela D M Kashuba David F Katz
author_sort	Oranat Chuchuen
title	Quantitative analysis of microbicide concentrations in fluids, gels and tissues using confocal Raman spectroscopy.
title_short	Quantitative analysis of microbicide concentrations in fluids, gels and tissues using confocal Raman spectroscopy.
title_full	Quantitative analysis of microbicide concentrations in fluids, gels and tissues using confocal Raman spectroscopy.
title_fullStr	Quantitative analysis of microbicide concentrations in fluids, gels and tissues using confocal Raman spectroscopy.
title_full_unstemmed	Quantitative analysis of microbicide concentrations in fluids, gels and tissues using confocal Raman spectroscopy.
title_sort	quantitative analysis of microbicide concentrations in fluids, gels and tissues using confocal raman spectroscopy.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/4a8d884fc32a4cb48752e72f8e037c57
work_keys_str_mv	AT oranatchuchuen quantitativeanalysisofmicrobicideconcentrationsinfluidsgelsandtissuesusingconfocalramanspectroscopy AT marcushhenderson quantitativeanalysisofmicrobicideconcentrationsinfluidsgelsandtissuesusingconfocalramanspectroscopy AT craigsykes quantitativeanalysisofmicrobicideconcentrationsinfluidsgelsandtissuesusingconfocalramanspectroscopy AT minsungkim quantitativeanalysisofmicrobicideconcentrationsinfluidsgelsandtissuesusingconfocalramanspectroscopy AT angeladmkashuba quantitativeanalysisofmicrobicideconcentrationsinfluidsgelsandtissuesusingconfocalramanspectroscopy AT davidfkatz quantitativeanalysisofmicrobicideconcentrationsinfluidsgelsandtissuesusingconfocalramanspectroscopy
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Quantitative analysis of microbicide concentrations in fluids, gels and tissues using confocal Raman spectroscopy.

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