The model is easily adapted to studying different active ingredients and delivery vehicles simply by changing the data entered, the researchers said. For example, researchers might specify the thickness of the expected coating layer, the initial concentration of microbicide in that layer, and the microbicide's documented ability to bind to and disable the viral particles.
The researchers demonstrated their new tool by applying it to the promising microbicide Cyanovirin-N, a protein with anti-HIV activity that has been well documented by other scientists.
"Our results suggest HIV neutralization is achievable if coating thicknesses on the order of 100 microns remain in place after sex," Geonnotti said. One hundred microns is the approximate width of a human hair. "Increased microbicide concentration and potency hasten viral neutralization and diminish penetration of infectious virus through the coating layer, as do ingredients that restrict viral passage," he said.
"Our findings demonstrate the need to pair potent active ingredients with well-engineered delivery vehicles, and they highlight the importance of the dosage form -- especially its ability to restrict viral diffusion and remain in place -- in microbicide effectiveness," Katz added.
More than 20 microbicidal chemical compounds are now in development or testing and five of them have reached the final phase of clinical trials. The Duke group's new model provides a "rational guide" for design specifications that could further improve such microbicides' ability to cut the rate of HIV spread, the researchers said.
The researchers now are conducting studies to experimentally measure the diffusion of viral particles through various delivery vehicles. They also are collaborating with other researchers on developing high-performance polymer gels that might provide a more substantial physical barrier to HIV.
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Source:Duke University