title: Enhanced activity of carbosilane dendrimers against HIV when combined with reverse transcriptase inhibitor drugs: searching for more potent microbicides.
abstract: Self-administered topical microbicides or oral preexposure prophylaxis could be very helpful tools for all risk groups to decrease the human immunodeficiency virus (HIV)-1 infection rates. Up until now, antiretrovirals (ARVs) have been the most advanced microbicide candidates. Nevertheless, the majority of clinical trials has failed in HIV-1 patients. Nanotechnology offers suitable approaches to develop novel antiviral agents. Thereby, new nanosystems, such as carbosilane dendrimers, have been shown to be safe and effective compounds against HIV with great potential as topical microbicides. In addition, because most of the attempts to develop effective topical microbicides were unsuccessful, combinatorial strategies could be a valid approach when designing new microbicides. We evaluated various combinations of anionic carbosilane dendrimers with sulfated (G3-S16) and naphthyl sulfonated (G2-NF16) ended groups with different ARVs against HIV-1 infection. The G3-S16 and G2-NF16 dendrimers showed a synergistic or additive activity profile with zidovudine, efavirenz, and tenofovir in the majority of the combinations tested against the X4 and R5 tropic HIV-1 in cell lines, as well as in human primary cells. Therefore, the combination of ARVs and polyanionic carbosilane dendrimers enhances the antiviral potency of the individual compounds, and our findings support further clinical research on combinational approaches as potential microbicides to block the sexual transmission of HIV-1.
authors.affiliation: Laboratorio InmunoBiología Molecular, Hospital General Universitario Gregorio Marañón, Madrid, Spain ; Instituto de Investigación Sanitaria del Gregorio Marañón, Madrid, Spain ; Networking Research Center on Bioengineering, Biomaterials and Nanomedicine, (CIBER-BBN), Madrid, Spain.
authors.forename: Enrique
authors.initials: E
authors.lastname: Vacas-Córdoba
authors.affiliation: Networking Research Center on Bioengineering, Biomaterials and Nanomedicine, (CIBER-BBN), Madrid, Spain ; Dendrimers for Biomedical Applications Group (BioInDen), University of Alcalá, Madrid, Spain.
authors.forename: Marta
authors.initials: M
authors.lastname: Galán
authors.affiliation: Networking Research Center on Bioengineering, Biomaterials and Nanomedicine, (CIBER-BBN), Madrid, Spain ; Dendrimers for Biomedical Applications Group (BioInDen), University of Alcalá, Madrid, Spain.
authors.forename: Francisco J
authors.initials: FJ
authors.lastname: de la Mata
authors.affiliation: Networking Research Center on Bioengineering, Biomaterials and Nanomedicine, (CIBER-BBN), Madrid, Spain ; Dendrimers for Biomedical Applications Group (BioInDen), University of Alcalá, Madrid, Spain.
authors.forename: Rafael
authors.initials: R
authors.lastname: Gómez
authors.affiliation: Laboratorio InmunoBiología Molecular, Hospital General Universitario Gregorio Marañón, Madrid, Spain ; Instituto de Investigación Sanitaria del Gregorio Marañón, Madrid, Spain ; Networking Research Center on Bioengineering, Biomaterials and Nanomedicine, (CIBER-BBN), Madrid, Spain.
authors.forename: Marjorie
authors.initials: M
authors.lastname: Pion
authors.affiliation: Laboratorio InmunoBiología Molecular, Hospital General Universitario Gregorio Marañón, Madrid, Spain ; Instituto de Investigación Sanitaria del Gregorio Marañón, Madrid, Spain ; Networking Research Center on Bioengineering, Biomaterials and Nanomedicine, (CIBER-BBN), Madrid, Spain.
authors.forename: M Ángeles
authors.initials: MÁ
authors.lastname: Muñoz-Fernández
mesh_terms: D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D050091:Dendrimers / Q000737:chemistry / Q000494:pharmacology*; D004357:Drug Synergism; D015658:HIV Infections; D015497:HIV-1 / Q000187:drug effects*; D006801:Humans; D018894:Reverse Transcriptase Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D012821:Silanes / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D050091:Dendrimers; D018894:Reverse Transcriptase Inhibitors; D012821:Silanes; C504072:carbosilane
keywords: HIV; antiretroviral; carbosilane dendrimer; microbicides; synergy
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