Spermicides examined in microbicide research
April 1, 1999
Spermicides examined in microbicide research
Spermicides such as nonoxynol-9 (N-9) are being examined as researchers explore development of vaginal microbicides. A nonionic detergent, N-9 is familiar to family planners in its use in over-the-counter spermicide preparations. Used as a contraceptive for decades, N-9 was grandfathered into federal Food and Drug Administration regulations under the monograph process.
Questions continue to swirl around N-9 use, and the push is on for definitive answers. Epithelial disruption could be affected by the dose, delivery system, or frequency of use of N-9.1 In the laboratory, N-9 is lethal to organisms that cause gonorrhea, genital herpes, trichomoniasis, syphilis, and HIV.2 However, findings from human studies have been inconsistent, say authors of the chapter on vaginal spermicides in Contraceptive Technology.3
Research disappointment and hopes
The most recent study reported that the use of an N-9 vaginal film (manufactured by Apothecus Pharmaceutical Corp. of Oyster Bay, NY) did not reduce the rate of new HIV, gonorrhea, or chlamydia infection in a group of sex workers who used condoms and received treatment for sexually transmitted diseases.4 The double-blind, placebo-controlled study included 1,292 HIV- negative female sex workers in Cameroon who were randomly assigned to use a film containing 70 mg of N-9 or a placebo film, inserted into the vagina before intercourse. Participants also were offered condoms.
As pointed out in Contraceptive Technology Update’s lead article last month, the definitive answer on N-9 has yet to appear. In different formulations or different strengths, the spermicide may provide the level of safe, effective protection needed in a vaginal microbicide. In the meantime, researchers are exploring its use, along with other spermicides, as an effective female-controlled protection product.
Novavax, with offices in Columbia and Rock ville, MD, has developed a chemical delivery system that give its products the look and feel of cosmetics rather than gel, says Craig Wright, MD, an infectious disease specialist and founder of the company. Novavax is examining the use of its non-phospholipid lipisome technology with several different types of spermicides and microbicides, says Wright. The National Institutes of Health (NIH) in Bethesda is funding Phase I research of two products: one with a 4% concentration of N-9, and a second with a combination of octoxynol-9 and tributyl phosphate.
New use for familiar substance
The Center for Biomedical Research at the Population Council in New York City has performed lab tests on a compound derived from red seaweed, combined with N-9, an effort to develop a spermicide that will protect against HIV and pregnancy. The compound, carrageenan, is used in such food products as ice cream and soup. It does not kill microbes, but it averts infection by binding to the surface of such viruses as HIV and prevents the microbes from adhering to cells.
Population Council researchers have developed a carrageenan gel that is effective over a wide pH range, retains its properties at high temperatures, and remains effective for hours in the vagina. It is not absorbed by the body, so researchers say it should not cause any systemic effects. The council’s researchers have tested the carrageenan/N-9 formulation vaginally in mice against herpes simplex virus-2. They also have examined carrageenan alone and in tandem with N-9 in rectal studies in mice.
Combining spermicides
A novel gel formulation containing low amounts of two spermicides, octoxynol-9 and benzalkonium chloride, is being evaluated for contraceptive and STD protection. According to Stephen Hayter, president/CEO of Empyrean Bioscience in Phoenix, in vitro studies show the formulation to be effective in killing HIV, herpes, hepatitis B, syphilis, gonorrhea, chlamydia, and trichomoniasis. In vivo safety studies also show the product will not cause vaginal or urethral irritation.
The ingredients act in synergy to attack HIV, an enveloped virus, explains Hayter. Octoxynol-9 attacks the envelope itself, reduces the surface tension, and allows the benzalkonium chloride to enter and destroy the virus.
He says the product, called Preventx, is scheduled to enter a Phase III trial funded and conducted by the National Institutes of Health’s National Institute of Allergy and Infectious Diseases. The first part of the trial will determine the product’s effectiveness in stopping pregnancy and halting the transmission of chlamydia and gonorrhea, with the second portion to focus specifically on HIV and other STDs.
The Advantage-S bioadhesive contraceptive gel, developed by Columbia Laboratories of Miami, consists of a patented bioadhesive carrier system and 52.5 mg of N-9. Family planners may remember this product as Advantage-24. (See CTU, April 1995, p. 45.) A Phase III clinical study sponsored by UNAIDS began in May 1996 to test the Advantage-S formulation in the prevention of HIV and STDs in about 2,000 women. The NIH is performing similar testing in Africa.
Protectaid, marketed in Canada by Axcan Pharma in Mont-Saint-Hilaire, Quebec, Canada, is being considered as a vaginal microbicide. The product is a vaginal sponge containing low levels of N-9 and benzalkonium chloride. Researchers also are looking at pre-coating such barrier devices as diaphragms and cervical cap with spermicide for use in female-controlled STD protection.
References
1. Howe JE, Minkoff HL, Duerr AC. Contraceptives and HIV. AIDS 1994; 8:861-871.
2. Elias CJ, Coggins C. Female-controlled methods to prevent sexual transmission of HIV. AIDS 1996; 10(suppl): S43-S51.
3. Hatcher RA, Trussell J, Stewart F, et al. Contraceptive Technology. 17th edition. New York: Ardent Media; 1998.
4. Roddy RE, Zekeng L, Ryan KA, et al. A controlled trial of nonoxynol-9 film to reduce male-to-female transmission of sexually transmitted diseases. N Engl J Med 1998; 339: 504-510.
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