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

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Creator
  • Moench, Thomas R
    • Other Affiliation: ReProtect, Inc
  • Mumper, Russell J.
    • Affiliation: Eshelman School of Pharmacy, Center for Nanotechnology in Drug Delivery
  • Hoen, Timothy E
    • Other Affiliation: Johns Hopkins University
  • Sun, Mianmian
    • Affiliation: Eshelman School of Pharmacy, Center for Nanotechnology in Drug Delivery
  • Cone, Richard A
    • Other Affiliation: Johns Hopkins University
Abstract
  • 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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  • Article
Rights statement
  • In Copyright
Rights holder
  • Thomas R Moench et al.; licensee BioMed Central Ltd.
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Journal title
  • BMC Infectious Diseases
Journal volume
  • 10
Journal issue
  • 1
Page start
  • 331
Language
  • English
Is the article or chapter peer-reviewed?
  • Yes
ISSN
  • 1471-2334
Bibliographic citation
  • BMC Infectious Diseases. 2010 Nov 18;10(1):331
Publisher
  • BioMed Central Ltd
Access right
  • Open Access
Date uploaded
  • July 15, 2016

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