Dendrimers, a new class of candidate topical microbicides with activity against herpes simplex virus infection

Dendrimers are large highly branched macromolecules synthesized from a poly functional core. They have shown a variety of biological properties, includ ing, in some instances, antiviral activity. In this study, five dendrimers were evaluated for in vitro activity against herpes simplex virus (HSV) typ es I 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 add ed to the cells prior to the addition of virus. Antiviral activity was redu ced or lost in the PR assays, in which the cells were incubated with the vi rus 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 applicatio n against genital HSV infection in mice. Two of the compounds, BRI-2999 and BRI-6741, significantly reduced infection rates when 15 mu l of a 100-mg/m l solution was administered immediately prior to intravaginal challenge, an d the most effective compound, BRI-2999, provided significant protection ev en when applied 30 min before challenge. This is the first report of microb icidal activity by dendrimers in vivo.