title: Liposomes for HIV prophylaxis.
abstract: There are approximately 33.4 million adults living with HIV worldwide of which an estimated 15.7 million are women. Although there has been enormous progress in the therapy of HIV/AIDS, treatment is not curative. Prevention is therefore of paramount importance, but vaccine-based and microbicidal approaches are still in their infancy. Since women acquire the virus largely through sexual intercourse, we developed liposomal systems potentially suitable for intra-vaginal use to prevent HIV-1 infection. We formulated liposomes from a range of naturally-occurring and synthetic lipids with varying physicochemical properties, and tested their ability to inhibit infection of transformed cells that express receptors specific to the virus. We identified formulations with the most favorable balance between decreasing HIV infection and causing cytotoxicity (i.e. therapeutic index). The therapeutic index improved with increasing cardiolipin content, and degree of unsaturation. Tissue reaction to these formulations was benign after intra-vaginal instillation in an in vivo female mouse model. These results support the potential use of cardiolipin-based liposomes enriched with synthetic lipids as microbicides for the prevention of HIV infection in women.
authors.affiliation: Laboratory for Biomaterials and Drug Delivery, Department of Anesthesiology, Division of Critical Care Medicine, Childrens Hospital Boston, Harvard Medical School, 300 Longwood Avenue, Boston, MA 02115, USA.
authors.forename: Nikita K
authors.initials: NK
authors.lastname: Malavia
authors.forename: David
authors.initials: D
authors.lastname: Zurakowski
authors.forename: Avi
authors.initials: A
authors.lastname: Schroeder
authors.forename: Amy M
authors.initials: AM
authors.lastname: Princiotto
authors.forename: Anna R
authors.initials: AR
authors.lastname: Laury
authors.forename: Hila E
authors.initials: HE
authors.lastname: Barash
authors.forename: Joseph
authors.initials: J
authors.lastname: Sodroski
authors.forename: Robert
authors.initials: R
authors.lastname: Langer
authors.forename: Navid
authors.initials: N
authors.lastname: Madani
authors.forename: Daniel S
authors.initials: DS
authors.lastname: Kohane
mesh_terms: D000818:Animals; D001672:Biocompatible Materials; D005260:Female; D015658:HIV Infections / Q000517:prevention & control*; D006801:Humans; D008081:Liposomes; D051379:Mice
chemical_list: D001672:Biocompatible Materials; D008081:Liposomes