Synergistic activity of carbosilane dendrimers in combination with maraviroc against HIV in vitro
Enrique Vacas Córdoba, Eduardo Arnáiz, F. Javier de la Mata, Rafael Gómez, Manuel Leal, Marjorie Pion, María Ángeles Muñoz‐Fernández
Abstract
Enrique Vacas Córdoba, Eduardo Arnáiz, F. Javier de la Mata, Rafael Gómez, Manuel Leal, Marjorie Pion, María Ángeles Muñoz‐Fernández
Abstract
OBJECTIVE: Dendrimers have been shown as effective and safe anti-HIV compounds with great potential as topical microbicides. Currently, the most advanced microbicides are based on antiretrovirals. However, nowadays none of them has shown any success in clinical trials. DESIGN: Antiviral activity and combinatorial profile of different combinations between CCR5 co-receptor antagonist, maraviroc (MRV), and polyanionic carbosilane dendrimers against HIV-1 strains were evaluated. METHODS: Cellular in-vitro models were used to evaluate the antiviral action of combinations of carbosilane dendrimers/MRV against CCR5 and dual tropic viral strains in TZM.bl cells and peripheral blood mononuclear cells. Combinatorial analysis was performed using Calcusyn software. RESULTS: In the majority of combinations tested, dendrimers showed synergistic profile with MRV against CCR5 and dual tropic HIV-1. CONCLUSION: The evaluated two-drug combinations increase their antiviral potency supporting further clinical investigations to develop combinatorial formulated topical microbicides to fight against the worldwide HIV spread.
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OBJECTIVE: Dendrimers have been shown as effective and safe anti-HIV compounds with great potential as topical microbicides. Currently, the most advanced microbicides are based on antiretrovirals. However, nowadays none of them has shown any success in clinical trials. DESIGN: Antiviral activity and combinatorial profile of different combinations between CCR5 co-receptor antagonist, maraviroc (MRV), and polyanionic carbosilane dendrimers against HIV-1 strains were evaluated. METHODS: Cellular in-vitro models were used to evaluate the antiviral action of combinations of carbosilane dendrimers/MRV against CCR5 and dual tropic viral strains in TZM.bl cells and peripheral blood mononuclear cells. Combinatorial analysis was performed using Calcusyn software. RESULTS: In the majority of combinations tested, dendrimers showed synergistic profile with MRV against CCR5 and dual tropic HIV-1. CONCLUSION: The evaluated two-drug combinations increase their antiviral potency supporting further clinical investigations to develop combinatorial formulated topical microbicides to fight against the worldwide HIV spread.
Key concepts: Maraviroc, CCR5 receptor antagonist, Microbicides for sexually transmitted diseases, Dendrimer, Microbicide, In vitro, Pharmacology, Potency