Comparison of microbicides for efficacy in protecting mice against vaginal challenge with herpes simplex virus type 2, cytotoxicity, antibacterial properties, and sperm immobilization.

BACKGROUND: Currently, a number of different over-the-counter spermicides and potential microbicides under development are in various phases of clinical trials. It is difficult to know how the various formulations would compare with each other or how efficacious they would be because no existing microbicides are commercially available. GOAL: To evaluate, in a standardized manner, various parameters of potential microbicides. STUDY DESIGN: In an effort to make a comprehensive comparison, several potential microbicides and over-the-counter vaginal products were assayed for their efficacy in protecting mice from infection by herpes simplex virus type 2 (HSV-2), for their cytotoxicity to human vaginal epithelial cells, for their effect on the growth rate of L acidophilus, and for their spermicidal activity. Test formulations were K-Y Plus, Gynol II, Advantage S, Replens, BufferGel, No Fertil, Carrageenan, and PC-550. Additionally, several formulations were evaluated for their use as a possible placebo in microbicide clinical trials. RESULTS: The formulations tested fell into three categories of efficacy in protecting mice from HSV-2 infection. The most efficacious were Carraguard and PC-550. All the other test formulations except methyl cellulose afforded varying degrees of protection against herpes simplex virus-2 infection. It was found that formulations containing the surfactant N9 had a cytotoxic effect on human vaginal cells, inhibited the growth rate of L acidophilus, and exhibited spermicidal activity. In addition, it was found that Replens, BufferGel, No Fertil, and the Carbopol formulation might have some effect on sperm motility. Also, K-Y Jelly significantly inhibited the growth rate of L acidophilus. CONCLUSION: Evaluating formulations under the same testing conditions can help to distinguish among potential formulations that are likely to show promise as safe and effective microbicides.

Nonoxynol-9 causes rapid exfoliation of sheets of rectal epithelium.

Nonoxynol-9 (N-9) containing spermicides and other N-9 containing products are commonly used as lubricants during rectal intercourse. We have previously demonstrated that rectal application of N-9 products in mice can cause exfoliation of epithelial cells, increasing the probability of infection by HSV-2. To determine if N-9-containing products would have a similar effect on the rectal epithelium in humans, the application of K-Y Plus and ForPlay, both over-the-counter (OTC) N-9 products, were compared to the application of two formulations, carrageenan and methyl cellulose, that do not contain N-9. The effects of each formulation were evaluated in 4 human participants. Light and electron microscope examination of rectal lavage specimens collected 15 min post application of N-9 products revealed the presence of sheets of epithelium. Each sheet contained hundreds of epithelial cells that included columnar and goblet cells, varieties of cells typical of rectal epithelial morphology. Sheets of epithelium were not observed in rectal lavage specimens collected 8 to 12 hr post N-9 product use or in either of the timed lavages involving non-N-9 containing formulations. In addition, no sheets of epithelial cells were observed in the baseline lavage specimens. We conclude that the rectal use of N-9-containing products causes a rapid exfoliation of extensive areas of the rectal epithelium. Exfoliation of the epithelium is no longer observed at 8 hr. It is reasonable to assume that the loss of the protective epithelium would render a person more at risk for infection by HIV and other sexually transmitted pathogens. We, therefore, caution against the use of N-9-containing products during rectal intercourse.

Pushing the frontiers of science--the Population Council's Microbicide Basic Science Network on vaginal microbicide research.

Microbicides are the new frontier of products for the prevention of sexually transmitted infections (STIs). Twelve years ago, scientists realized that existing spermicides had some anti-microbial activity and perhaps could be improved or reformulated with new compounds to provide a complete barrier against STIs. However, the development and successful marketing of an effective, non-toxic, convenient and affordable vaginal microbicide that women can use on a long-term basis hinges on a close collaboration between research institutions and the pharmaceutical industry. The Population Council has recently taken the first step in instituting a multifaceted strategy for the development of a microbicide by establishing the Microbicide Basic Science Network, comprising of scientists with diverse backgrounds and expertize.

Carrageenan-based nonoxynol-9 spermicides for prevention of sexually transmitted infections.

BACKGROUND AND OBJECTIVES: Carrageenan-based nonoxynol-9 (N-9)-containing formulations were developed in response to the concern that over the counter (OTC) spermicides may not protect people from HIV infection and other sexually transmitted pathogens. GOAL OF THIS STUDY: The goal of this study was to compare the efficacy of carrageenan-based formulations to OTC spermicides in protecting mice from infection by herpes simplex virus 2 (HSV-2). STUDY DESIGN: Mice were challenged with vaginal inoculation of HSV-2 after pretreatment with test formulations. RESULTS: Carrageenan-based formulations were significantly more effective than currently marketed spermicides containing the same amount of N-9. Efficacy was demonstrated over a wide pH range. The carrageenan-based formulations could be autoclaved without losing antiviral activity and remained active in the vagina for several hours. CONCLUSIONS: We conclude that carrageenan-based N-9 formulations are likely to provide a more significant degree of protection against HSV-2 and other enveloped viruses than current OTC spermicides while providing comparable spermicidal activity.