title: Triple combination of carbosilane dendrimers, tenofovir and maraviroc as potential microbicide to prevent HIV-1 sexual transmission.
abstract: OBJECTIVE
  To research the synergistic activity by triple combinations of carbosilane dendrimers with tenofovir and maraviroc as topical microbicide.
  
  
  METHODS
  Cytotoxicity, anti-HIV-1 activity, vaginal irritation and histological analysis of triple combinations were determined. Analysis of combined effects and the median effective concentration were performed using CalcuSyn software.
  
  
  RESULTS
  Combinations showed a greater broad-spectrum anti-HIV-1 activity than the single-drug, and preserved this activity in acid environment or seminal fluid. The strongest combinations were G2-STE16/G2-S24P/tenofovir, G2-STE16/G2-S16/maraviroc and G2-STE16/tenofovir/maraviroc at 2:2:1, 10:10:1 10:5:1 ratios, respectively. They demonstrated strong synergistic activity profile due to the weighted average combination indices varied between 0.06 and 0.38. No irritation was detected in female BALB/c mice.
  
  
  CONCLUSIONS
  The three-drug combination increases their antiviral potency and act synergistically as potential microbicide.
authors: Laboratorio InmunoBiología Molecular, Hospital General Universitario Gregorio Marañón, Instituto de Investigación Sanitaria Gregorio Marañón, Spanish HIV-HGM Biobank, Networking Research Center on Bioengineering, Biomaterials & Nanomedicine (CIBER-BBN), Madrid, Spain.
authors: Daniel
authors: D
authors: Sepúlveda-Crespo
authors: Javier
authors: J
authors: Sánchez-Rodríguez
authors: María Jesús
authors: MJ
authors: Serramía
authors: Rafael
authors: R
authors: Gómez
authors: Francisco Javier
authors: FJ
authors: De La Mata
authors: José Luis
authors: JL
authors: Jiménez
authors: Ma Ángeles
authors: MÁ
authors: Muñoz-Fernández
mesh_terms: D000225:Adenine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D000818:Animals; D019380:Anti-HIV Agents / Q000008:administration & dosage*; D000890:Anti-Infective Agents / Q000008:administration & dosage*; D000998:Antiviral Agents / Q000627:therapeutic use; D002470:Cell Survival; D003510:Cyclohexanes / Q000008:administration & dosage*; D050091:Dendrimers / Q000737:chemistry; D004338:Drug Combinations; D005260:Female; D015658:HIV Infections / Q000517:prevention & control* / Q000635:transmission; D015497:HIV-1 / Q000187:drug effects; D006801:Humans; D000077592:Maraviroc; D051379:Mice; D008807:Mice, Inbred BALB C; D009092:Mucous Membrane / Q000187:drug effects; D063065:Organophosphonates / Q000008:administration & dosage*; D012821:Silanes / Q000008:administration & dosage*; D012984:Software; D000068698:Tenofovir; D014230:Triazoles / Q000008:administration & dosage*; D014621:Vagina / Q000187:drug effects* / Q000821:virology
chemical_list: D019380:Anti-HIV Agents; D000890:Anti-Infective Agents; D000998:Antiviral Agents; D003510:Cyclohexanes; D050091:Dendrimers; D004338:Drug Combinations; D063065:Organophosphonates; D012821:Silanes; D014230:Triazoles; C504072:carbosilane; D000068698:Tenofovir; D000225:Adenine; D000077592:Maraviroc
keywords: HIV-1; carbosilane dendrimer; maraviroc; microbicide; nanomedicine; synergy; tenofovir; triple combination; vaginal irritation