"Molecular Condom" Holds Promise in the Fight against HIV/AIDS

Scientists at the University of Utah and Duke University designed a "molecular condom" that women could use daily to prevent AIDS. The condom consists of a vaginally inserted liquid that turns into a gel-like coating and then, when exposed to semen, returns to liquid form and releases an antiviral drug.

"We have developed a new vaginal gel that we call a molecular condom because it is composed of molecules that are liquid at room temperature and, when applied in the vagina, will spread and turn into a gel and effectively coat the tissue," says Patrick Kiser, an assistant professor of bioengineering at the University of Utah. "It's a smart molecular condom because we designed this gel to release anti-HIV drugs when the gel comes into contact with semen during intercourse."

"The ultimate hope for this technology is to protect women and their unborn or nursing children from the AIDS virus," but the molecular condom is five years away from tests in humans and roughly 10 years from widespread use, said Kiser, who completed his doctoral work at Duke University’s Pratt School of Engineering.

Kiser and colleagues, including David Katz of the Pratt School and Duke University Medical Center, report development of the molecular condom in a study published online Monday, Dec. 11, 2006, in the Journal of Pharmaceutical Sciences. The current study follows a recent report by Katz’s team detailing a computer model that can predict the effectiveness of various "microbicidal" recipes in destroying HIV before it reaches vulnerable body tissues.

The advances are part of a worldwide research effort to develop microbicides – drug-delivery systems such as gels, rings, sponges or creams to prevent infection by the human immunodeficiency virus and other sexually transmitted diseases. HIV causes AIDS, which cripples the immune system, leaving patients vulnerable to other infections, cancers and death.

Microbicides are seen as a way for women to gain power by protecting themselves from HIV, particularly in impoverished nations where AIDS is widespread, where rape is rampant or where conventional condoms are taboo, not reliably available or where men resist using them. Worldwide, most AIDS cases are spread heterosexually.

About 16 microbicides are in development and five are undergoing testing in thousands of women, mostly in Africa. They are designed to fight HIV infection by preventing the virus from entering cells or replicating, or by maintaining acidic vaginal conditions. No first-generation microbicide has been approved yet for wide use.

Delivering Anti-HIV Medicine When and Where Needed

Kiser says the molecular condom would be a more advanced method of delivering an antiviral drug to prevent infection by the AIDS virus.

"Up until now, most of the microbicide work has focused on the development of the active drug, not on the delivery of the drug," Kiser says. "This study and other work in my lab are directed at developing new technologies for vaginal delivery of antiviral agents, particularly a microbicide that can respond to triggers [body temperature and semen] that are present before, during and after intercourse. This is the first paper that begins to point in that direction."

Kiser says the dosage of anti-HIV drugs in first-generation microbicides lasts only a few hours, so "you have to use them an hour before sex, which is difficult. You only need one failure to get the disease. We're shooting for a microbicide delivery system that would be used once a day or once a month."

In the study, Kiser and colleagues outline how they designed a water-based gel or "hydrogel" sensitive to body temperature and pH (acidity or alkalinity) so that it could serve as a "smart semen-triggered vaginal microbiocidal vehicle."

The researchers have not yet tried incorporating an antiviral drug into the hydrogel, but showed that in laboratory conditions, the substance turns from a liquid to a gel at body temperature, then returns to liquid form and can release test compounds – stand-ins for antiAIDS drugs – when exposed to semen, which has a pH of 7.5, more alkaline than the acidic vaginal pH of 4 to 5.

A Burst of Anti-AIDS Medicine

Kiser, Gupta and colleagues demonstrated how the polymer could change from liquid to gel at body temperature, then return to liquid form when exposed to simulated seminal fluid – a sticky mixture of sugars and salt–— and release large and small molecules used as stand-ins for real medicines in drug-delivery experiments.

In the experiments, when the hydrogel molecular condom was exposed to mock seminal fluid, it released 49 percent of the small-molecule drug within five minutes and 81 percent within an hour. It released 48 percent of the large molecule drug within 30 minutes and 66 percent in 90 minutes.

The lab experiments were designed to make it difficult for the molecular condom to release simulated drugs, Kiser says. Inside a woman, the gel would be much thinner than in the lab tests, so antiviral drugs "would all be released in just a few minutes."

Kiser hopes to incorporate experimental anti-AIDS drugs known as entry inhibitors into the molecular condom.

Kiser conducted the research with University of Utah bioengineering graduate students Kavita Gupta and Meredith Roberts, and undergraduates Scott Barnes and Rachel Tangaro. The research is part of Gupta's doctoral thesis, and she did much of the work. Other coauthors of the study were bioengineers Katz and Derek Owen, of Duke’s Pratt School of Engineering. The National Institutes of Health funded the study.