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Prevention vaginally of HIV-1 transmission in humanized BLT mice and mode of antiviral action of polyanionic carbosilane dendrimer G2-S16

Abstract The development of a safe, effective, and low-priced topical microbicide to prevent HIV-1 sexual transmission is urgently needed. The emerging field of nanotechnology plays an important role in addressing this challenge. We demonstrate that topical vaginal administration of 3% G2-S16 preven...

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Published in:Nanomedicine 2015-08, Vol.11 (6), p.1299-1308
Main Authors: Sepúlveda-Crespo, Daniel, PhD, Serramía, María Jesús, MLT, Tager, Andrew M., PhD, Vrbanac, Vladimir, PhD, Gómez, Rafael, PhD, De La Mata, Francisco Javier, PhD, Jiménez, José Luis, PhD, Muñoz-Fernández, Mª Ángeles, PhD, MD
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Language:English
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Summary:Abstract The development of a safe, effective, and low-priced topical microbicide to prevent HIV-1 sexual transmission is urgently needed. The emerging field of nanotechnology plays an important role in addressing this challenge. We demonstrate that topical vaginal administration of 3% G2-S16 prevents HIV-1JR-CSF transmission in humanized (h)-BLT mice in 84% with no presence of HIV-1 RNA and vaginal lesions. Second-generation polyanionic carbosilane dendrimer G2-S16 with silica core and 16 sulfonate end-groups exerts anti-HIV-1 activity at an early stage of viral replication, blocking the gp120/CD4 interaction, acting on the virus, and inhibiting the cell-to-cell HIV-1 transmission, confirming its multifactorial and non-specific ability. This study represents the first demonstration that transmission of HIV-1 can be efficiently blocked by vaginally applied G2-S16 in h-BLT mice. These findings provide a step forward in the development of G2-S16-based vaginal microbicides to prevent vaginal HIV-1 transmission in humans. From the Clinical Editor HIV infections remain a significant problem worldwide and the major route of transmission is through sexual activity. In this article, the authors developed an antiviral agent containing polyanionic carbosilane dendrimer with silica core and 16 sulfonate end-groups. When applied vaginally, this was shown to exert anti-HIV protection. These positive findings may offer hope in the fight against the spread of HIV epidemic.
ISSN:1549-9634
1549-9642
DOI:10.1016/j.nano.2015.04.013