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Science circles in on vaginal ring technology
What if a vaginal ring could deliver protection against unplanned pregnancy and HIV infection? Scientists are testing a ring loaded with multiple antiviral drugs to prevent HIV infection, and they also are weighing its use in pregnancy prevention.1
Researchers at Weill Cornell Medical College in New York City have looked at rings made of biosoluble acacia gum or nonbiodegradable hydrogel of 2-hydroxyethyl methacrylate and sodium methacrylate.2 For pregnancy prevention purposes, they are testing a three-pronged approach, using nonhormonal compounds such as ferrous gluconate to cause spermiostasis, l-ascorbic acid to increase the viscosity of the cervical mucus, and mixtures of polyamino and polycarboxylic acids to sustain vaginal pH close to 4.5, which is healthy for the vagina but inhospitable for sperm. Inventors of the ring technology include Brij Saxena, PhD, professor of reproductive biology and endocrinology, and Mukul Singh, MD, PhD, associate research professor of obstetrics and gynecology, both at Weill Cornell Medical College, and Sidney Lerner of BioRings in New York City.
Early tests of the nonhormonal compounds in the hydrogel formulation in rabbits indicated the potential for the development of a biocompatible, nonhormonal, intravaginal contraceptive device.3 To test the ring's effectiveness in preventing HIV infection, researchers looked at incorporating the reverse transcriptase inhibitors TMC120, PMPA, 3'-azido-3'-deoxythymidine, and a new anti-HIV agent, Boc-lysinated betulinic acid, into vaginal rings with different combinations. Scientists used high-performance liquid chromatography, gas chromatography, or immunoassay to determine daily and cumulative release rates of the inhibitors. Anti-HIV effects were measured by assessment of p24 Gag antigen in T-cell cultures exposed to HIV-1 isolates. These anti-HIV agents, when combined, were found to block infection in human cells exposed to the virus in a laboratory setting.1
"We realize if we use more than one anti-HIV agent, we are able to act at different steps of the life cycle of the virus and become much more potent than if we only use one," says Saxena.
Researchers are now working toward approval and funding of a comprehensive trial of the ring formulation for pregnancy and HIV protection. Use of the ring will empower women to protect themselves on two fronts, state Saxena and Singh.
Nestorone ring moves up
Scientists at the Population Council, a New York City-based research organization, have closed data collection on a Phase III trial of a vaginal ring using a combination of the progestin Nestorone with ethinyl estradiol. The trial closed in December 2008, while a six-month follow-up looked at return to fertility in women who were desiring to become pregnant after the trial or who were planning to use a nonhormonal contraceptive, says Ruth Merkatz, RN, PhD, the Population Council's director of clinical development.
The council's vaginal ring is a thin, flexible product made of silicone rubber that delivers Nestorone, a synthetic progestin similar to the natural hormone progesterone, and a low dose of ethinyl estradiol. The ring inhibits ovulation by continuously releasing a low dose of hormones through the vaginal walls and then the bloodstream. Earlier research indicates the ring, used on a regimen of 21 days in and seven days out, provided women safe and effective contraception.4 "The ring permits the diffusion of the drug out into the bloodstream, and you can get very rapid blood levels through that system for a very rapid effect," observes Merkatz.
The Population Council ring under development is designed to be used for one year. This timing differs from the Ortho Evra (Ortho Women's Health & Urology; Raritan, NJ), which calls for a new ring after three weeks of use. A product that is purchased only once a year might result in lower costs and fewer trips to a medical provider or pharmacy, say Population Council officials. With fewer to manufacture and fewer to discard, a product that is replaced annually also could have a reduced impact on the environment, they note.5
Researchers must analyze the collected data and prepare them for submission to the Food and Drug Administration (FDA) in the form of a New Drug Application. Using the safety and efficacy data collected and other information, the FDA will decide whether the product can be approved for use in the United States.