Material Issues for The Molding of Silicones to Control the Kinetics of Release of Antiretroviral Drugs through Intravaginal Ring

Christian Carrot 1 Meriam Memmi 2 Marlène Desloir 1 Blaise Figuereo 2 Thomas Bourlet 2 Bruno Pozzetto 1
1UMR CNRS 5223, Universite de Lyon
2Groupe Immunite des Muqueuses et Agents Pathogenes, Universite de Lyon

The propagation of HIV-1 infection represents a major problem of public health, notably in sub-Saharian Africa where about six out of ten infected adults are women. Among the new options of preventive therapy, antiretroviral drugs used as microbicides distributed via an intravaginal ring (IVR) constitutes an original solution.The aim of this work was to set up a silicone IVR able to deliver simultaneously several drugs with the precise objective of determining if the release of each drug is possible with the used silicones.The crosslinking of various silicone combinations was followed by dynamic spectrometry in various temperature conditions in presence of Tenofovir, a usual antiretroviral drug that can be considered as efficient for protecting from a heterosexual HIV-1 infection. Issues related to possible inhibition of crosslinking by functional groups on the active molecule were raised. IVRs were made manually with siloxanes combining two elastomers before and after crosslinking, and were loaded with different concentrations of Tenofovir. The rings were then placed under conditions mimicking closely the physiological environment of the vagina. The amounts of released tenofovir were measured by UV spectrophotometry. Among the combinations of siloxanes that were used, only a few were shown to release amounts of tenofovir that can be considered as efficient for protecting from a heterosexual HIV-1 infection.The principle of simultaneaous release of more than one drug, owing to multi-reservoir IVR, manufactured by co-extrusion followed by molding will be decribed.









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