Triple combination of carbosilane dendrimers, tenofovir and maraviroc as potential microbicide to prevent HIV-1 sexual transmission

• Published in: Nanomedicine (London, England) England), 2015-03, Vol.10 (6), p.899-914
• Main Authors: Sepúlveda-Crespo, Daniel, Sánchez-Rodríguez, Javier, Serramía, María Jesús, Gómez, Rafael, De La Mata, Francisco Javier, Jiménez, José Luis, Muñoz-Fernández, Mª Ángeles
• Format: Article
• Language: English
• Subjects: Adenine - administration & dosage; Adenine - analogs & derivatives; Animals; Anti-HIV Agents - administration & dosage; Anti-Infective Agents - administration & dosage; Antiviral Agents - therapeutic use; carbosilane dendrimer; Cell Survival; Combination drug therapy; Cyclohexanes - administration & dosage; Dendrimers; Dendrimers - chemistry; Dosage and administration; Drug Combinations; Drug therapy; Female; Health aspects; HIV infections; HIV Infections - prevention & control; HIV Infections - transmission; HIV-1; HIV-1 - drug effects; Human immunodeficiency virus 1; Humans; Infection control; Maraviroc; Methods; Mice; Mice, Inbred BALB C; microbicide; Mucous Membrane - drug effects; nanomedicine; Organophosphonates - administration & dosage; Prevention; Silanes - administration & dosage; Software; synergy; Tenofovir; Triazoles - administration & dosage; triple combination; Vagina - drug effects; Vagina - virology; vaginal irritation
• ISSN: 1743-5889; 1748-6963
• DOI: 10.2217/nnm.14.79

To research the synergistic activity by triple combinations of carbosilane dendrimers with tenofovir and maraviroc as topical microbicide. 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. 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. The three-drug combination increases their antiviral potency and act synergistically as potential microbicide.