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. 2022 Mar 21;20(1):151.
doi: 10.1186/s12951-022-01350-8.

Safety and efficacy of G2-S16 dendrimer as microbicide in healthy human vaginal tissue explants

I Rodríguez-Izquierdo  1   2   3 , M J Serramía  1   2 , R Gómez  4   5 , G Espinosa  6 , M Genebat  7   8 , M Leal  9 , M A Muñoz-Fernandez  10   11   12
Affiliations

Safety and efficacy of G2-S16 dendrimer as microbicide in healthy human vaginal tissue explants

I Rodríguez-Izquierdo et al. J Nanobiotechnology. .

Abstract

Background: The absence of an effective treatment and vaccine in HIV-1 pandemic place preventive strategies such as safety and effective microbicide development as a central therapeutic approach to control HIV-1 pandemic nowadays.

Results: Studies of cytotoxicity, immune population status, inflammation or tissue damage and mainly prophylactic inhibition of HIV-1 infection in vaginal human explants demonstrate the biosafety and effectivity of G2-S16 dendrimer. Human explants treated with G2-S16 dendrimer or treated and HIV-1 infected do not presented signs of irritation, inflammation, immune activation or T cell populations deregulation.

Conclusions: Herein we conclude that G2-S16 dendrimer has demonstrated sufficient efficacy, biosafety, effectivity and behavior in the closest to the real-life condition model represented by the human healthy donor vaginal tissue explants, to raise G2-S16 dendrimer as a promising candidate to clinical trials to develop an effective microbicide against HIV-1 infection.

Keywords: Efficacy; G2-S16; HIV-1; Microbicide; Safety; Vaginal explants.

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Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
Biocompatibility of G2-S16 dendrimer. A Schematic representation of ETP processing. B Biocompatibility of G2-S16 dendrimer at 5 days. C Tissue viability after 48 h or 5 days post-infection. Data represent mean of n = 3 (B) and n = 5 (C) different ectocervix tissue explants made by duplicate (4 ETP/conditions). Graphics B and C represent tissue viability ± SD. NT Non-treated ETP, DPI days post-infection
Fig. 2
Fig. 2
G2-S16 dendrimer inhibition of HIV-1 infection. ETP of ectocervix explants were infected with HIV-1 THRO T/F isolate or treated with G2-S16 dendrimer 3 mM and infected. Tissue viability measured by MTT assay and HIV-1 inhibition titrated on TZM.bl reporter cell line after 2 or 5 DPI were represented. Bars represent the mean of 5 different ectocervix tissue explants made by duplicate (4 ETP/condition) ± SD. NT non-treated, DPI days post-infection
Fig. 3
Fig. 3
Lymphocyte relative abundance in tissue explants. A Representative flow cytometry analysis of CD4 and CD8 abundance in ETP after HIV-1 infection and G2-S16 dendrimer 3 mM treatment (upper panels) or HIV-1 infection solely (lower panels) B Analysis of ectocervix explant T cell population relative abundance (n = 5 ectocervix explants) performed on 4 ETP/condition
Fig. 4
Fig. 4
Effect of G2-S16 dendrimer treatment on T cell activation. ETPs were treated with G2-S16 dendrimer 3 mM, digested, disaggregated and analyzed by flow cytometry for T cell activation markers. Data represent effect on G2-S16 dendrimer on ETP T cell activation markers on T cell CD4 + and CD8+ populations. Bars represent the mean of 5 ectocervix explants ± SD
Fig. 5
Fig. 5
Histopathological analysis. Total accumulative score of each ETP analyzed (Lower graphic). Data represent summary of each individual damage score analyzed for ETP non-treated or G2-S16 dendrimer 3 mM treatment. N9 4.5% was used as tissue damage control. (Upper graphic) Representative images of normal vaginal ectocervix tissue (Left graphic) and Representative images of non-treated ETP (A, D) G2-S16 3 mM treatment (B, E) and N9 4.5% (C, F). Each represented point corresponds to ETP vaginal explants. NT non-treated; N9 Nonoxinol-9; 4.5% w/v
Fig. 6
Fig. 6
G2-S16 polyanionic carbosilane dendrimer. Schematic representation of G2-S16 dendrimer and synthesis
See this image and copyright information in PMC

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