US scientists have developed an HIV-blocking gel made from a polymer that women can use as a vaginal “molecular condom”: the gel becomes semi-solid in the presence of semen and traps the AIDS-causing virus in its microscopic mesh. However it will be several years before the gel is available since clinical trials in humans would have to be done first.
The new material was developed by scientists at the University of Utah in Salt Lake City. A paper about how they tested the gel and how it traps HIV particles will be published online later this week in the journal Advanced Functional Materials. Co-authors include researchers from Northwestern University in Chicago who helped track the movement of HIV in the gel.
The paper’s senior author Dr Patrick Kiser, an associate professor of bioengineering at the University of Utah’s College of Engineering, told the press that:
“The first step in the complicated process of HIV (human immunodeficiency virus) infection in a woman is the virus diffusing from semen to vaginal tissue.”
We want to stop that first step. We have created the first vaginal gel designed to prevent movement of the AIDS virus. This is unique. There’s nothing like it,” he added.
Kiser explained that they wanted to develop technologies that enabled women to protect themselves against HIV without having to persuade their partners to do it. He said this was important in the under-resourced countries like sub-Sahara Africa and south Asia where in some areas the rate of HIV infection among women is as high as 60 per cent.
First author Julie Jay, who is working toward a doctorate in pharmaceutics and pharmaceutical chemistry at the university said:
“Due to cultural and socioeconomic factors, women often are unable to negotiate the use of protection with their partner.”
She explained that she, Kiser, and the rest of the team developed a vaginal gel that the woman would insert a few hours before sex. The gel detects the presence of semen and acts as a barrier between HIV and vaginal tissue, effectively stopping the virus from infecting vaginal cells.
“We wanted to build a gel that would stop HIV from interacting with vaginal tissue,” said Kay.
The effort to develop a range of intravaginal gels, rings and films to prevent the spread of AIDS is not new but it has reached an impasse: few have reached clinical trials in Africa, and those have failed to stop virus transmission. This was either because the anti-virals they were delivering were too weak or did not last long enough, or because patients just didn’t use them. Also, some of the gels increased the risk of transmission, possibly because they irritated the lining of the vagina, causing immune cells to concentrate in that area, which were then successfully targeted by the virus.
Kiser and colleagues have been working to develop a “molecular condom” for some years. In 2006 they published a paper on an earlier type of gel that was applied to the vagina as a liquid that became a gel at body temperature, and then became liquid again in the presence of semen, whereupon it released an anti-HIV drug.
But the problem with this earlier attempt was that in Africa, the high ambient temperatures stopped the gel from becoming liquid again, which stopped it coating the vaginal lining evenly. Also, there aren’t many antivirals that bind and attack HIV in the presence of semen.
So Kiser and colleagues went back to the drawing board. This time they came up with a new gel that works in the opposite way to the old one. The new gel responds to changes in pH (acidity or alkalinity) so that when it comes into contact with the less acidic semen it becomes a semi-solid instead of more liquid, and also forms a network of interlinked molecules like a mesh.
The gel is made of two polymers, PBA (phenylboronic acid) and SHA (salicylhydroxamic acid). Polymers are repeating patterns of long chain-like molecules, like a chemical “spaghetti”. In this case, imagine one type of spaghetti is made of PBA and the other is made of SHA, that under the normal acidity inside the vagina, where pH is around 4.8, the bonds between them are weak so the strands of spaghetti slip and slide around each other easily: and the gel remains a gel.
But when the environment becomes less acidic, and becomes increasingly alkaline, at around pH of 7.6, which is what the vaginal environment becomes in the presence of semen, the spaghetti strands of PBA and SHA stick together much more strongly, and the gel becomes semi-solid.
As Jay explained:
“It flows at a vaginal pH, and the flow becomes slower and slower as pH increases, and it begins to act more solid at the pH of semen.”
The scientists at Northwestern University in Chicago tracked the movement of the HIV in the gel. They marked the virus with a fluorescent dye and followed it with a sophisticated microscope and saw how its speed changed under different pH conditions.
Also, HIV moves slowly in the gel, even when the pH is low (acid) and the spaghetti strands of the two polymers are still slippery. However, the virus stops moving completely when pH is higher.
This is because the size of the mesh, the holes in the net, formed by the polymers as they bond to each other under higher pH is around 30 to 50 nanometers, while the HIV particle is about 100 nanometres wide.
It’s like catching pebbles with a tennis racket: the holes formed by the racket strings (the mesh) are just small enough to stop the stones (the HIV) falling through. To imagine how small this is, a human hair is 100,000 nanometres thick: in the tennis racket analogy, that would be about the size of the tennis court.
Kiser said they think the gel should block other viruses and sperm: perhaps it could be used as a contraceptive, or to stop infections by herpes viruses and HPV, the human papillomavirus that causes cervical cancer.
Taking the concept further, if the gel stops the HIV getting into cells, then perhaps it can also act as a barrier against immune cells getting near HIV. AIDS develops when HIV hijacks immune system cells.
Kiser said another option would be to add anti-AIDS drugs like tenofovir to the gel. Tenofovir is not like the antivirals they tested with the old gel, it protects immune cells from infection.
“The virus would have two barriers to get through: the polymer barrier and then the drug barrier,” he explained.
After sex, any residual HIV particles would become inactive because the vagina would return to normal acidity, which they don’t like, and the remaining antiviral in the gel would still work as a barrier to some extent.
The researchers hope that human trials will start in three to five years, and then the gel will be available a few years after that. They want the gel to contain antivirals that both block HIV and stop it replicating.
Sources: University of Utah.
Written by: Catharine Paddock, PhD