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Microbicide excipients can greatly increase susceptibility to genital herpes transmission in the mouse

BACKGROUND: Several active ingredients proposed as vaginal microbicides have been shown paradoxically to increase susceptibility to infection in mouse genital herpes (HSV-2) vaginal susceptibility models and in clinical trials. In addition, "inactive ingredients" (or excipients) used in to...

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Autores principales: Moench, Thomas R, Mumper, Russell J, Hoen, Timothy E, Sun, Mianmian, Cone, Richard A
Formato: Texto
Lenguaje:English
Publicado: BioMed Central 2010
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2996397/
https://www.ncbi.nlm.nih.gov/pubmed/21087496
http://dx.doi.org/10.1186/1471-2334-10-331
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author Moench, Thomas R
Mumper, Russell J
Hoen, Timothy E
Sun, Mianmian
Cone, Richard A
author_facet Moench, Thomas R
Mumper, Russell J
Hoen, Timothy E
Sun, Mianmian
Cone, Richard A
author_sort Moench, Thomas R
collection PubMed
description BACKGROUND: Several active ingredients proposed as vaginal microbicides have been shown paradoxically to increase susceptibility to infection in mouse genital herpes (HSV-2) vaginal susceptibility models and in clinical trials. In addition, "inactive ingredients" (or excipients) used in topical products to formulate and deliver the active ingredient might also cause epithelial toxicities that increase viral susceptibility. However, excipients have not previously been tested in susceptibility models. METHODS: Excipients commonly used in topical products were formulated in a non-toxic vehicle (the "HEC universal placebo"), or other formulations as specified. Twelve hours after exposure to the excipient or a control treatment, mice were challenged with a vaginal dose of HSV-2, and three days later were assessed for infection by vaginal lavage culture to assess susceptibility. RESULTS: The following excipients markedly increased susceptibility to HSV-2 after a single exposure: 5% glycerol monolaurate (GML) formulated in K-Y(® )Warming Jelly, 5% GML as a colloidal suspension in phosphate buffered saline, K-Y Warming Jelly alone, and both of its humectant/solvent ingredients (neat propylene glycol and neat PEG-8). For excipients formulated in the HEC vehicle, 30% glycerin significantly increased susceptibility, and a trend toward increased HSV-2 susceptibility was observed after 10% glycerin, and 0.1% disodium EDTA, but not after 0.0186% disodium EDTA. The following excipients did not increase susceptibility: 10% propylene glycol, 0.18%, methylparaben plus 0.02% propylparaben, and 1% benzyl alcohol. CONCLUSIONS: As reported with other surfactants, the surfactant/emulsifier GML markedly increased susceptibility to HSV-2. Glycerin at 30% significantly increased susceptibility, and, undiluted propylene glycol and PEG-8 greatly increased susceptibility.
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spelling pubmed-29963972010-12-03 Microbicide excipients can greatly increase susceptibility to genital herpes transmission in the mouse Moench, Thomas R Mumper, Russell J Hoen, Timothy E Sun, Mianmian Cone, Richard A BMC Infect Dis Research Article BACKGROUND: Several active ingredients proposed as vaginal microbicides have been shown paradoxically to increase susceptibility to infection in mouse genital herpes (HSV-2) vaginal susceptibility models and in clinical trials. In addition, "inactive ingredients" (or excipients) used in topical products to formulate and deliver the active ingredient might also cause epithelial toxicities that increase viral susceptibility. However, excipients have not previously been tested in susceptibility models. METHODS: Excipients commonly used in topical products were formulated in a non-toxic vehicle (the "HEC universal placebo"), or other formulations as specified. Twelve hours after exposure to the excipient or a control treatment, mice were challenged with a vaginal dose of HSV-2, and three days later were assessed for infection by vaginal lavage culture to assess susceptibility. RESULTS: The following excipients markedly increased susceptibility to HSV-2 after a single exposure: 5% glycerol monolaurate (GML) formulated in K-Y(® )Warming Jelly, 5% GML as a colloidal suspension in phosphate buffered saline, K-Y Warming Jelly alone, and both of its humectant/solvent ingredients (neat propylene glycol and neat PEG-8). For excipients formulated in the HEC vehicle, 30% glycerin significantly increased susceptibility, and a trend toward increased HSV-2 susceptibility was observed after 10% glycerin, and 0.1% disodium EDTA, but not after 0.0186% disodium EDTA. The following excipients did not increase susceptibility: 10% propylene glycol, 0.18%, methylparaben plus 0.02% propylparaben, and 1% benzyl alcohol. CONCLUSIONS: As reported with other surfactants, the surfactant/emulsifier GML markedly increased susceptibility to HSV-2. Glycerin at 30% significantly increased susceptibility, and, undiluted propylene glycol and PEG-8 greatly increased susceptibility. BioMed Central 2010-11-18 /pmc/articles/PMC2996397/ /pubmed/21087496 http://dx.doi.org/10.1186/1471-2334-10-331 Text en Copyright ©2010 Moench et al; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Moench, Thomas R
Mumper, Russell J
Hoen, Timothy E
Sun, Mianmian
Cone, Richard A
Microbicide excipients can greatly increase susceptibility to genital herpes transmission in the mouse
title Microbicide excipients can greatly increase susceptibility to genital herpes transmission in the mouse
title_full Microbicide excipients can greatly increase susceptibility to genital herpes transmission in the mouse
title_fullStr Microbicide excipients can greatly increase susceptibility to genital herpes transmission in the mouse
title_full_unstemmed Microbicide excipients can greatly increase susceptibility to genital herpes transmission in the mouse
title_short Microbicide excipients can greatly increase susceptibility to genital herpes transmission in the mouse
title_sort microbicide excipients can greatly increase susceptibility to genital herpes transmission in the mouse
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2996397/
https://www.ncbi.nlm.nih.gov/pubmed/21087496
http://dx.doi.org/10.1186/1471-2334-10-331
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