PHASED BY SEMEN: A new polymer designed to fight HIV is liquid at room temperature [top] but turns semisolid at vaginal pH and temperature [bottom left] and liquefies again in response to the neutral pH of semen [bottom right].
JUDIT FABIAN, University of Utah

As part of a worldwide project to dramatically curtail the spread of AIDS, researchers have developed a vaginal gel designed to liquefy and release an antiviral drug when exposed to semen. Creators of the "molecular condom," still in very early testing, say the temperature- and pH-sensitive polymer could prove a more efficient way to deliver an anti-HIV drug than normal gels and creams.

"What we hope is that by attacking the virus in semen, we can inactivate it before it has any chance of permeating the tissue," says bioengineer Patrick Kiser of the University of Utah.

Kiser and his colleagues developed a polymer mixture that is liquid at room temperature, but thickens into a gellike coating at body temperature and a pH of 4 to 5, which occurs in the vagina. The researchers designed the gel to liquefy again at neutral PH, because semen neutralizes vaginal PH. Kiser says it can then mix with semen and deliver a desired antiviral payload, perhaps a small molecule or a polymer microbicide (microbe-killing compound).

The molecular condom is part of a global effort to come up with microbicides suspended in creams, gels or other materials to prevent the spread of the human immunodeficiency virus and other sexually transmitted diseases. Clinical trials are ongoing for at least a dozen different vaginal microbicides, according to the Alliance for Microbicide Development.

The trick, Kiser says, is to introduce such compounds as rapidly and as effectively as possible. "It could really only take minutes for the virus to come into contact with immune system cells," he explains, "so you don't really have a lot of time."

The molecular condom appears to be a relatively nontoxic way of quickly delivering an antiviral drug, according to a study by Kiser and his co-workers published online December 11 by the Journal of Pharmaceutical Sciences. The researchers report that it destroyed fewer mouse skin cells in the lab dish than two other products applied vaginally, including the routinely used spermicide nonoxynol-9.

The polymer also released 49 percent of a small dye molecule, which is chemically similar to some microbicides, within five minutes of exposure to a fluid that simulates semen, they found. Kiser warned, however, that researchers still must determine whether the gel causes any potentially dangerous side effects such as inflammation, which would attract immune cells that could serve as added targets for HIV infection.

The gel's staying power is yet to be determined, but Kiser says that based on its viscosity, it may remain in the vagina for up to a day. Retention time is key, he notes: "If a woman has to apply a microbicide right before sex, that's quite inconvenient."

"It's an exciting new way to think about things," says Polly Harrison, director of the Alliance for Microbicide Development. "We want to make these products as user-friendly as possible," and a gel that women could apply well in advance of sex "could be a real advantage."