Efficacy of carbosilane dendrimers with an antiretroviral combination against HIV-1 in the presence of semen-derived enhancer of viral infection

García-Broncano, Pilar; Ceña-Díez, Rafael; Mata, F. Javier de la; Gómez, Rafael; Resino, Salvador; Muñoz‐Fernández, María Ángeles

doi:10.1016/j.ejphar.2017.05.060

Cited by 23 publications

(11 citation statements)

References 50 publications

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“…G2-S16 has been proven to block HIV infection in multiple cell lines and human primary blood cells Chonco et al [19]. This dendrimer inhibits infection even in the presence of semen, a known infection enhancer [17, 39], as well as the cell-to-cell transmission and syncytium formation [40]. On the other hand, the biosafety of this nanocompound has been tested not only in vitro but also ex vivo and in vivo [19, 20, 38].…”

Section: Discussionmentioning

confidence: 99%

G2-S16 dendrimer microbicide does not interfere with the vaginal immune system

et al. 2019

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It is essential that prophylactic drugs do not interfere with the normal function of the immune system. The use of nanoparticles as vaginal microbicides is a promising prevention strategy against sexually transmitted infections. With that aim, our group is working with the G2-S16, a second generation carbosilane dendrimer with sulfonate groups in the periphery, which has been previously shown to be effective against HIV-1 and HSV-2 infection, and it is now on the road to clinical trials. Our objective in this new study is to assess the effects of G2-S16 on the immune barrier of the female reproductive tract. The expression of differentiation, maturation and activation markers was measured in epithelial cells, dendritic cells, M and GM macrophages, and T cells using RT-qPCR and flow cytometry. The results demonstrate that G2-S16 does not alter the natural immunity of the vagina, strongly supporting the biosafety of this dendrimer for clinical use.

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Section: Discussionmentioning

confidence: 99%

G2-S16 dendrimer microbicide does not interfere with the vaginal immune system

et al. 2019

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“…To assess the activity of G2-S16 polyanionic carbosilane dendrimer in presence of semen, Vero cells were seeded in 24-well plates at 1.75 × 10 5 cells/well and expose to maximum non-toxic concentration for G2-S16 dendrimer (10 µM) [17]. HSV-2 was incubated for 10 min with semen (10%) or PBS as described previously [17,23]. After the semen/HSV-2 incubation, the Vero cells were infected with HSV-2/semen inoculum at MOI 0.001.…”

Section: Efficacy Of G2-s16 Polyanionic Carbosilane Dendrimer Againstmentioning

confidence: 99%

Cationic Dendrimer G2-S16 Inhibits Herpes Simplex Type 2 Infection and Protects Mice Vaginal Microbiome

et al. 2020

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The G2-S16 polyanionic carbosilane dendrimer is a promising microbicide that inhibits HSV-2 infection in vitro and in vivo in mice models. This G2-S16 dendrimer inhibits HSV-2 infection even in the presence of semen. Murine models, such as BALB/c female mice, are generally used to characterize host-pathogen interactions within the vaginal tract. However, the composition of endogenous vaginal flora remains largely undefined with modern microbiome analyses. It is important to note that the G2-S16 dendrimer does not change healthy mouse vaginal microbiome where Pseudomonas (10.2–79.1%) and Janthinobacterium (0.7–13%) are the more abundant genera. The HSV-2 vaginally infected female mice showed a significant microbiome alteration because an increase of Staphylococcus (up to 98.8%) and Escherichia (30.76%) levels were observed becoming these bacteria the predominant genera. BALB/c female mice vaginally-treated with the G2-S16 dendrimer and infected with the HSV-2 maintained a healthy vaginal microbiome similar to uninfected female mice. Summarizing, the G2-S16 polyanionic carbosilane dendrimer inhibits the HSV-2 infection in the presence of semen and prevents the alteration of mice female vaginal microbiome.

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“…The drug molecule can be either entrapped inside the structure or linked to the external functional groups. This approach was proposed for the carrying of several anti HIV agents [52,53,54,55].…”

Section: Drug Protection Nanosystemsmentioning

confidence: 99%

“…A drug combination including TDF into dendrimers was designed for the evaluation in an in vitro model of semen-enhanced viral infection. The results obtained suggested that this therapeutic strategy could bypass the detrimental effects of amyloid fibrils, present in semen, which seem responsible of the failure of topical vaginal gels action [54]. An approach to the treatment of neuro-AIDS was based on the use of co-encapsulated drugs into ultra-small iron oxide NPs with the addition of dextran sulfate.…”

Section: Nucleoside Reverse Transcriptase Inhibitors Nanosystemsmentioning

confidence: 99%

Reverse Transcriptase Inhibitors Nanosystems Designed for Drug Stability and Controlled Delivery

et al. 2019

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An in-depth analysis of nanotechnology applications for the improvement of solubility, distribution, bioavailability and stability of reverse transcriptase inhibitors is reported. Current clinically used nucleoside and non-nucleoside agents, included in combination therapies, were examined in the present survey, as drugs belonging to these classes are the major component of highly active antiretroviral treatments. The inclusion of such agents into supramolecular vesicular systems, such as liposomes, niosomes and lipid solid NPs, overcomes several drawbacks related to the action of these drugs, including drug instability and unfavorable pharmacokinetics. Overall results reported in the literature show that the performances of these drugs could be significantly improved by inclusion into nanosystems.

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Efficacy of carbosilane dendrimers with an antiretroviral combination against HIV-1 in the presence of semen-derived enhancer of viral infection

Cited by 23 publications

References 50 publications

G2-S16 dendrimer microbicide does not interfere with the vaginal immune system

G2-S16 dendrimer microbicide does not interfere with the vaginal immune system

Cationic Dendrimer G2-S16 Inhibits Herpes Simplex Type 2 Infection and Protects Mice Vaginal Microbiome

Reverse Transcriptase Inhibitors Nanosystems Designed for Drug Stability and Controlled Delivery

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