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Antimicrobial Agents and Chemotherapy, September 2000, p. 2471-2474, Vol. 44, No. 9
0066-4804/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

Dendrimers, a New Class of Candidate Topical Microbicides with Activity against Herpes Simplex Virus Infection

N. Bourne,1,* L. R. Stanberry,1 E. R. Kern,2 G. Holan,3 B. Matthews,3 and D. I. Bernstein1

Division of Infectious Diseases, Children's Hospital Medical Center, Cincinnati, Ohio 45229-3039,1 Department of Pediatrics, University of Alabama School of Medicine, Birmingham, Alabama 35294,2 and Biomolecular Research Institute, Clayton 3186, Victoria, Australia3

Received 16 February 2000/Returned for modification 23 May 2000/Accepted 22 June 2000

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 µl 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.

* Corresponding author. Mailing address: Children's Hospital Medical Center, Division of Infectious Diseases, 3333 Burnet Ave., Cincinnati, OH 45229. Phone: (513) 636-7666. Fax: (513) 636-7655. E-mail: bourn0{at}chmcc.org.

Antimicrobial Agents and Chemotherapy, September 2000, p. 2471-2474, Vol. 44, No. 9
0066-4804/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.


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