These hollow particles seemed
to work with minimal tweaking.
HIV vaccines are in their infancy, and effective microbicides to prevent sexual transmission of HIV still don’t exist. Women, making up nearly half of the world’s 33 million HIV cases, are especially in need of protection. Here’s a new possible way for women to protect themselves before sex: an applicator filled with specially formulated fatty particles called liposomes.
The tiny spheres measure 4 microns in diameter, not visible without a microscope, and consist of a double outer layer of lipids (fats) and hollow centers. They’re relatively easy and cheap to engineer, and thus present a viable option for developing countries, where the cost of anti-HIV drugs, while falling, still bars access for most people.
In tests reported online this month in the journal Biomaterials, liposomes inhibited HIV infection in cell culture and appeared safe in female mice when given intravaginally.
Curiously, while liposomes can be loaded with drugs or other compounds, they seemed to work quite well on their own.
“We had been planning do much more complex things, like putting ligands on the surface to increase binding to HIV,” says Daniel Kohane, director of theLaboratory for Biomaterials and Drug Delivery at Children’s Hospital Boston, who led the study. “It was a surprise that liposomes alone worked so well. Simplicity is always better.”
Funded by the Grand Challenges in Global Health initiative and the National Institutes of Health, Kohane and colleagues made an assortment of liposomes using different kinds of fats, then screened them systematically in cell cultures. They hit on several formulations that effectively blocked HIV infection without being toxic. Best were liposomes containing cardiolipin, a fat first found in animal hearts; they performed even better with the addition of a synthetic phospholipid.
So how do they work? Kohane and colleagues don’t really know. More tests are planned, but what’s clear is that the particles bind to HIV, so they might interfere with the virus’s ability to fuse with cell membranes, the first step in infection.
“The idea, simplistically, is that liposomes look like cell membranes,” says Kohane, “so maybe we could use them as decoys to prevent HIV infection.”
Many microbicides can irritate and compromise the vaginal lining, increasing the risk of HIV transmission. Tested in female mice, liposomes caused little or no inflammation, and imaging confirmed that they stayed in place or left the body, but didn’t travel beyond the vagina.
Though some intravaginal anti-HIV compounds are in the pipeline, none are available yet. Kohane hopes to get further funding to test liposomes in other animal models. Besides being inexpensive, they’re easy to formulate into ointments or gels, and are stable for long periods of time, making them well suited to resource-poor settings.
“Women in areas such as sub-Saharan Africa often cannot control their male partners’ use of condoms, making them three times more likely to be HIV-positive than men,” notes Nikita Malavia, the study’s first author, who worked in Kohane’s lab and in the lab of Robert Langer of MIT. “This technology could enable women to take control in their own hands.”
Ed note: Read a profile of Kohane.
Nancy Fliesler, Vector’s editor, has been senior science writer at Children’s Hospital Boston since 2003, spotting innovation trends and covering virtually every clinical and laboratory research department in the hospital. She previously worked for the ABC News medical unit, helped produce science programs for K-8 teachers for the Harvard-Smithsonian Science Media Group, and worked on video productions for the Mental Illness Education Project. Prior to that, she was executive editor of Journal Watch, and also produced and directed the award-winning documentary Lifestyles of the Poor and Unknown. She holds a BA from Oberlin College (Phi Beta Kappa) and an MS in science and medical journalism from Boston University.
