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We have identified a short amphipathic helical peptide, called C5A, which exhibits potent microbicidal activitiesin vitro and which offers protection from vaginal HIV transmissionin vivo in a humanized mouse model. However, there are many obstacles to overcome before C5A can be considered a true microbicidal candidate. First, it must be stabilized against enzymatic degradation in a continuously warm and moist environment. Second, it must be delivered in a controlled manner to achieve long-term and coitally independent efficacy. We demonstrate in thisin vitro study that the combination of two matrices with different subliming properties ((hexamethylcyclotrisiloxane [HMCS] and cyclododecane [CDD]) containing 10% labile C5A yielded the best results in terms of controlled release and preserved anti-HIV activity of the peptide when pre-exposed to cell-free medium or cell culture at body temperature for up to 2 months.

Sublimable C5A Delivery Provides Sustained and Prolonged Anti-HIV Microbicidal Activities