Triple combination of carbosilane dendrimers, tenofovir and maraviroc as potential microbicide to prevent HIV-1 sexual transmission. (March 2015)

• Record Type: Journal Article
• Authors: Sepúlveda-Crespo, Daniel; Sánchez-Rodríguez, Javier; Serramía, María Jesús; Gómez, Rafael; De La Mata, Francisco Javier; Jiménez, José Luis; Muñoz-Fernández, Mª Ángeles
• Is Part Of: Nanomedicine. Volume 10:Number 6(2015)
• Page Start: 899
• Page End: 914
• Publication Date: 2015-03
• Subjects: carbosilane dendrimer -- HIV-1 -- maraviroc -- microbicide -- nanomedicine -- synergy -- tenofovir -- triple combination -- vaginal irritation; Nanotechnology -- Periodicals; Medical technology -- Periodicals; Nanotechnology -- Therapeutic use -- Periodicals; 610.28
• DOI: 10.2217/nnm.14.79
• Languages: English
• ISSNs: 1743-5889

Abstract

Aim: 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.Conclusion: The three-drug combination increases their antiviral potency and act synergistically as potential microbicide.