Polyanionic Functionalized Carbosilane Dendrimers As Potential Microbicides To Prevent Hiv-1 Sexual Transmission

AIDS Research and Human RetrovirusesVol. 30, No. S1 Evaluation of Novel Compounds in Cell-Based SystemsFree AccessPolyanionic Functionalized Carbosilane Dendrimers as Potential Microbicides to Prevent HIV-1 Sexual TransmissionEnrique Vacas-Córdoba, Francisco J. De la Mata, Rafael Gómez, Marjorie Pion, and Ma Ángeles Muñoz-FernándezEnrique Vacas-CórdobaHospital General Universitario Gregorio Marañón, Laboratorio InmunoBiología Molecular, Madrid, SpainSearch for more papers by this author, Francisco J. De la MataUniversidad de Alcalá, Departamento de Química Inorgánica, Alcalá de Henares, SpainSearch for more papers by this author, Rafael GómezUniversidad de Alcalá, Departamento de Química Inorgánica, Alcalá de Henares, SpainSearch for more papers by this author, Marjorie PionHospital General Universitario Gregorio Marañón, Laboratorio InmunoBiología Molecular, Madrid, SpainSearch for more papers by this author, and Ma Ángeles Muñoz-FernándezHospital General Universitario Gregorio Marañón, Laboratorio InmunoBiología Molecular, Madrid, SpainSearch for more papers by this authorPublished Online:30 Oct 2014https://doi.org/10.1089/aid.2014.5442.abstractAboutSectionsPDF/EPUB Permissions & CitationsPermissionsDownload CitationsTrack CitationsAdd to favorites Back To Publication ShareShare onFacebookTwitterLinked InRedditEmail P33.04Background: Topical microbicides are researched as potential tools in order to stop the HIV sexual spreading in all risk groups. Since the majority of clinical trials in HIV-1 patients have failed, nanotechnology offers novel suitable approaches to develop new microbicidal compounds, such as dendrimers.Methods:In vitro and in vivo studies were performed to evaluate the safety, biocompatibility, anti-HIV ability and mechanism of two polyanionic carbosilane dendrimers. Moreover, the antiviral activity of carbosilane dendrimer/ARV combinations against R5, X4 and dual tropic HIV-1 isolates was evaluated in human primary cells and TZM.bl cell line using Calcusyn software.Results: Sulphated and naphthylsulfonated functionalized carbosilane dendrimers G3-S16 and G2-NF16 are shown as safety and effective compounds against HIV. They impede laboratory and clinical primary HIV-1 isolates infection in activated PBMC and inhibit HSV-2 infection in vitro. Dendrimers are able to inhibit viral infection at fusion and thus at the entry step. They impede the binding of viral particles to target cells surface and membrane fusion, through the blockage of gp120/CD4 interaction. In addition, dendrimers can inhibit cell-to-cell HIV transmission and difficult infectious synapse formation.G3-S16 or G2-NF16 did not produce changes in proinflammatory cytokines profile in treated epithelial cells, in PBMC proliferation, microbiota or sperm survival. Moreover, no irritation, inflammation or vaginal lesions were detected in female mice after dendrimers vaginal administration.As well, G3-S16 and G2-NF16 showed a synergistic activity profile with AZT, efavirenz, maraviroc and tenofovir in the majority of combinations tested against X4 and R5 tropic HIV-1 in cell lines as well as in primary human cells.Conclusions: Carbosilane dendrimers and their combinations with ARV can be effective antiviral agents, supporting further clinical research on these as potential microbicides in the context of blocking HIV-1 sexual transmission.FiguresReferencesRelatedDetailsCited byDendronized PLGA nanoparticles with anionic carbosilane dendrons as antiviral agents against HIV infection1 January 2016 | RSC Advances, Vol. 6, No. 77 Volume 30Issue S1Oct 2014 InformationCopyright 2014, Mary Ann Liebert, Inc.To cite this article:Enrique Vacas-Córdoba, Francisco J. De la Mata, Rafael Gómez, Marjorie Pion, and M Ángeles Muñoz-Fernández.Polyanionic Functionalized Carbosilane Dendrimers as Potential Microbicides to Prevent HIV-1 Sexual Transmission.AIDS Research and Human Retroviruses.Oct 2014.A204-A204.http://doi.org/10.1089/aid.2014.5442.abstractPublished in Volume: 30 Issue S1: October 30, 2014PDF download