title: Sublimable C5A delivery provides sustained and prolonged anti-HIV microbicidal activities.
abstract: We have identified a short amphipathic helical peptide, called C5A, which exhibits potent microbicidal activities in vitro and which offers protection from vaginal HIV transmission in 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 this in 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.
authors.affiliation: Department of Pharmaceutical Sciences, School of Pharmacy, Loma Linda University, Loma Linda, California, USA.
authors.forename: Richard
authors.initials: R
authors.lastname: Maskiewicz
authors.forename: Michael
authors.initials: M
authors.lastname: Bobardt
authors.forename: Udayan
authors.initials: U
authors.lastname: Chatterji
authors.forename: Simi
authors.initials: S
authors.lastname: Gunaseelan
authors.forename: Charlene S
authors.initials: CS
authors.lastname: Dezzutti
authors.forename: Francois
authors.initials: F
authors.lastname: Penin
authors.forename: Philippe A
authors.initials: PA
authors.lastname: Gallay
mesh_terms: D000998:Antiviral Agents / Q000737:chemistry / Q000494:pharmacology*; D002460:Cell Line; D002478:Cells, Cultured; D006678:HIV / Q000187:drug effects*; D006801:Humans; D010455:Peptides / Q000737:chemistry / Q000494:pharmacology*; D017433:Protein Structure, Secondary
chemical_list: D000998:Antiviral Agents; D010455:Peptides