Dendrimers are large highly branched macromolecules synthesized from a polyfunctional core. They have shown a variety of
biological properties, including, in some instances,
antiviral activity. In this study, five
dendrimers were evaluated for in vitro activity against herpes simplex virus (HSV) types 1 and 2 by cytopathic effect (CPE) inhibition and plaque reduction (PR) assay in human foreskin fibroblast cells. All of the compounds were active against both virus types in the CPE inhibition assay, in which
drug was added to the cells prior to the addition of virus.
Antiviral activity was reduced or lost in the PR assays, in which the cells were incubated with the virus before the
drug was added. The prophylactic efficacy suggested that the
dendrimers might have potential as
topical microbicides, products intended to be applied to the vaginal or rectal mucosa to protect against
sexually transmitted infections. Three
dendrimers were evaluated for this application against genital HSV
infection in mice. Two of the compounds,
BRI-2999 and
BRI-6741, significantly reduced
infection rates when 15 microl of a 100-mg/ml
solution was administered immediately prior to intravaginal challenge, and the most effective compound,
BRI-2999, provided significant protection even when applied 30 min before challenge. This is the first report of microbicidal activity by
dendrimers in vivo.