October 16, 2012
ARLINGTON, VA -- CONRAD researchers, in collaboration with engineers at the University of Utah, have designed a 90-day intravaginal ring that can be used by women to prevent the sexual transmission of HIV. A study of the ring used sheep to determine whether safe, effective and steady doses of the antiretroviral drug tenofovir can be released over 90 days. This research is being presented at the 2012 American Association of Pharmaceutical Scientists (AAPS) Annual Meeting and Exposition in Chicago, Ill., Oct. 14 – 18 and will be published in the 12th issue of Antimicrobial Agents and Chemotherapy.
Tenofovir is a drug commonly used by those infected with HIV to prevent the virus from multiplying in the immune system. A clinical study of women in South Africa who used a vaginal gel containing tenofovir has shown that it is almost 40 percent effective in reducing sexual transmission when used before and after sex, and 54% effective if used with every act of intercourse.
"We have developed a new intravaginal ring technology based on rubbery hydrogel plastics that are loaded with antiretroviral drugs. We can engineer the plastic so it can release a small quantity of drug per day, or a much larger quantity, depending on the drug being delivered,” said Patrick Kiser, Ph.D, the lead investigator at the University of Utah.
Vaginal rings have been used since the 1970s, and the possibility for reducing HIV infection has caused a burst of innovation in the field, using new materials and technologies.
"Most vaginal rings release a limited quantity of drug each day, but this ring can release quantities 1,000 times larger due to the selection of specific hydrophilic polymers with high permeability," said David Friend, Ph.D., director of Product Development at CONRAD, who is also an author on the work. "This study showed that the ring releases at least 10 mg of tenofovir a day over 90 days, which makes it very possible that it can be effective in preventing HIV infection in women.”
An intravaginal ring that can be worn for 90 days is crucial for adherence, as well as cost in low-income countries. Drugs are only effective when actually used as prescribed, and in the case of a ring containing an active drug that is inserted for 90 days, the problem of adherence is significantly reduced, at least for that time period.
The intravaginal ring used in the study is made from rubbery water swellable plastics that can be processed using techniques developed in the medical device industry. The tubing consists of plastic which is filled with a paste of tenofovir and glycerin. The tube is sealed shut and joined into a ring shape. The glycerol in the core brings fluid from the vagina that accelerates the drug delivery process.
"We directly compared the ring to 1 percent tenofovir gel, and the ring resulted in similar, if not higher, levels of drug in the vaginal tissue,” said Dr. Friend. “If the results in sheep hold up in humans, we would expect this ring to be highly protective against HIV.”
Gustavo Doncel, MD, Ph.D, executive director of CONRAD and a coauthor of the study said, "We are very excited about this new, improved delivery system for tenofovir, the only microbicide with proof of efficacy in animals and humans, and are working hard to move this product into the first clinical trial of a tenofovir ring next year."
Drs. Kiser and Friend conducted the study with colleagues at CONRAD including Meredith Clark, Ph.D, Dr. Doncel, and Neelima Chandra, PhD.; and graduate students Todd Johnson and Justin Clark; and undergraduate Ted Albright. This work was part of Johnson's Ph.D. thesis. The study was funded by USAID through a grant to CONRAD.
CONRAD was established in 1986 and is a Division of the Department of Obstetrics and Gynecology at Eastern Virginia Medical School (EVMS) in Norfolk, VA, where it has laboratories and a clinical research center. CONRAD is committed to improving reproductive health by researching and developing new contraceptive options and products to prevent HIV and sexually transmitted infections (STIs). The main office is located in Arlington, VA with collaborators around the world. www.conrad.org