Label-free analysis of tenofovir delivery to vaginal tissue using co-registered confocal Raman spectroscopy and optical coherence tomography.
Vaginally applied microbicide products offer a female-controlled strategy for preventing sexual transmission of HIV. Microbicide transport processes are central to their functioning, and there is a clear need for a better understanding of them. To contribute to that end, we developed an assay to ana...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2017-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC5621692?pdf=render |
| _version_ | 1818276498204786688 |
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| author | Oranat Chuchuen Jason R Maher Marcus H Henderson Michael Desoto Lisa C Rohan Adam Wax David F Katz |
| author_facet | Oranat Chuchuen Jason R Maher Marcus H Henderson Michael Desoto Lisa C Rohan Adam Wax David F Katz |
| author_sort | Oranat Chuchuen |
| collection | DOAJ |
| description | Vaginally applied microbicide products offer a female-controlled strategy for preventing sexual transmission of HIV. Microbicide transport processes are central to their functioning, and there is a clear need for a better understanding of them. To contribute to that end, we developed an assay to analyze mass transport rates of microbicide molecules within the epithelial and stromal layers of polarized vaginal mucosal tissue during contact with a gel vehicle. The assay utilizes a new diffusion chamber mounted in a custom instrument that combines confocal Raman spectroscopy and optical coherence tomography. This measures depth-resolved microbicide concentration distributions within epithelium and stroma. Data for a tenofovir gel were fitted with a compartmental diffusion model to obtain fundamental transport properties: the molecular diffusion and partition coefficients in different compartments. Diffusion coefficients in epithelium and stroma were computed to be 6.10 ± 2.12 x 10-8 and 4.52 ± 1.86 x 10-7 cm2/sec, respectively. The partition coefficients between epithelium and gel and between stroma and epithelium were found to be 0.53 ± 0.15 and 1.17 ± 0.16, respectively. These drug transport parameters are salient in governing the drug delivery performance of different drug and gel vehicle systems. They can be used to contrast drugs and vehicles during product design, development and screening. They are critical inputs to deterministic transport models that predict the gels' pharmacokinetic performance, which can guide improved design of products and optimization of their dosing regimens. |
| first_indexed | 2024-12-12T22:46:36Z |
| format | Article |
| id | doaj.art-803f4ae29a7048829df80abc61a94f56 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-12T22:46:36Z |
| publishDate | 2017-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-803f4ae29a7048829df80abc61a94f562022-12-22T00:09:11ZengPublic Library of Science (PLoS)PLoS ONE1932-62032017-01-01129e018563310.1371/journal.pone.0185633Label-free analysis of tenofovir delivery to vaginal tissue using co-registered confocal Raman spectroscopy and optical coherence tomography.Oranat ChuchuenJason R MaherMarcus H HendersonMichael DesotoLisa C RohanAdam WaxDavid F KatzVaginally applied microbicide products offer a female-controlled strategy for preventing sexual transmission of HIV. Microbicide transport processes are central to their functioning, and there is a clear need for a better understanding of them. To contribute to that end, we developed an assay to analyze mass transport rates of microbicide molecules within the epithelial and stromal layers of polarized vaginal mucosal tissue during contact with a gel vehicle. The assay utilizes a new diffusion chamber mounted in a custom instrument that combines confocal Raman spectroscopy and optical coherence tomography. This measures depth-resolved microbicide concentration distributions within epithelium and stroma. Data for a tenofovir gel were fitted with a compartmental diffusion model to obtain fundamental transport properties: the molecular diffusion and partition coefficients in different compartments. Diffusion coefficients in epithelium and stroma were computed to be 6.10 ± 2.12 x 10-8 and 4.52 ± 1.86 x 10-7 cm2/sec, respectively. The partition coefficients between epithelium and gel and between stroma and epithelium were found to be 0.53 ± 0.15 and 1.17 ± 0.16, respectively. These drug transport parameters are salient in governing the drug delivery performance of different drug and gel vehicle systems. They can be used to contrast drugs and vehicles during product design, development and screening. They are critical inputs to deterministic transport models that predict the gels' pharmacokinetic performance, which can guide improved design of products and optimization of their dosing regimens.http://europepmc.org/articles/PMC5621692?pdf=render |
| spellingShingle | Oranat Chuchuen Jason R Maher Marcus H Henderson Michael Desoto Lisa C Rohan Adam Wax David F Katz Label-free analysis of tenofovir delivery to vaginal tissue using co-registered confocal Raman spectroscopy and optical coherence tomography. PLoS ONE |
| title | Label-free analysis of tenofovir delivery to vaginal tissue using co-registered confocal Raman spectroscopy and optical coherence tomography. |
| title_full | Label-free analysis of tenofovir delivery to vaginal tissue using co-registered confocal Raman spectroscopy and optical coherence tomography. |
| title_fullStr | Label-free analysis of tenofovir delivery to vaginal tissue using co-registered confocal Raman spectroscopy and optical coherence tomography. |
| title_full_unstemmed | Label-free analysis of tenofovir delivery to vaginal tissue using co-registered confocal Raman spectroscopy and optical coherence tomography. |
| title_short | Label-free analysis of tenofovir delivery to vaginal tissue using co-registered confocal Raman spectroscopy and optical coherence tomography. |
| title_sort | label free analysis of tenofovir delivery to vaginal tissue using co registered confocal raman spectroscopy and optical coherence tomography |
| url | http://europepmc.org/articles/PMC5621692?pdf=render |
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