scholarly journals High Preventive Effect of G2-S16 Anionic Carbosilane Dendrimer against Sexually Transmitted HSV-2 Infection

Molecules ◽  
2020 ◽  
Vol 25 (13) ◽  
pp. 2965 ◽  
Author(s):  
Ignacio Rodriguez-Izquierdo ◽  
Samanta Gasco ◽  
Maria Angeles Muñoz-Fernández
Keyword(s):  
Vaginal Microbiome ◽  
Preventive Effect ◽  
Carbosilane Dendrimers ◽  
Sexually Transmitted ◽  
Essential Step ◽  
Carbosilane Dendrimer ◽  
Microbicide Development ◽  
Topical Microbicide

Anionic carbosilane dendrimers such as G2-S16 are very effective in preventing HSV-2 infection both in vitro and in vivo. We present the main achievements obtained for the G2-S16 dendrimer in vivo, especially related to its efficacy against HSV-2 infection. Moreover, we discuss the mechanisms by which the G2-S16 dendrimer applied vaginally as a topical microbicide has been demonstrated to be safe and harmless for the vaginal microbiome balance, as both conditions present an essential step that has to be overcome during microbicide development. This review points to the marked protective effect of the G2-S16 dendrimer against sexually transmitted HSV-2 infection, supporting its role as a possible microbicide against HSV-2 infection.

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

Pharmaceutics ◽  
2020 ◽  
Vol 12 (6) ◽  
pp. 515 ◽  
Author(s):  
Carlos Guerrero-Beltrán ◽  
Inmaculada Garcia-Heredia ◽  
Rafael Ceña-Diez ◽  
Ignacio Rodriguez-Izquierdo ◽  
María Jesús Serramía ◽  
...  
Keyword(s):  
Vaginal Microbiome ◽  
Murine Models ◽  
Healthy Mouse ◽  
Infected Female ◽  
Female Mice ◽  
Carbosilane Dendrimer ◽  
Vaginal Tract

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.

scholarly journals G2-S16 Polyanionic Carbosilane Dendrimer Can Reduce HIV-1 Reservoir Formation by Inhibiting Macrophage Cell to Cell Transmission

2021 ◽  
Vol 22 (16) ◽  
pp. 8366
Author(s):  
Ignacio Relaño-Rodríguez ◽  
María de la Sierra Espinar-Buitrago ◽  
Vanessa Martín-Cañadilla ◽  
Rafael Gómez-Ramírez ◽  
María Ángeles Muñoz-Fernández
Keyword(s):  
T Cells ◽  
Developed Countries ◽  
Main Role ◽  
Viral Particles ◽  
Carbosilane Dendrimer ◽  
Science Community ◽  
New Compounds ◽  
Hiv 1

Human immunodeficiency virus (HIV-1) is still a major problem, not only in developing countries but is also re-emerging in several developed countries, thus the development of new compounds able to inhibit the virus, either for prophylaxis or treatment, is still needed. Nanotechnology has provided the science community with several new tools for biomedical applications. G2-S16 is a polyanionic carbosilane dendrimer capable of inhibiting HIV-1 in vitro and in vivo by interacting directly with viral particles. One of the main barriers for HIV-1 eradication is the reservoirs created in primoinfection. These reservoirs, mainly in T cells, are untargetable by actual drugs or immune system. Thus, one approach is inhibiting HIV-1 from reaching these reservoir cells. In this context, macrophages play a main role as they can deliver viral particles to T cells establishing reservoirs. We showed that G2-S16 dendrimer is capable of inhibiting the infection from infected macrophages to healthy T CD4/CD8 lymphocytes by eliminating HIV-1 infectivity inside macrophages, so they are not able to carry infectious particles to other body locations, thus preventing the reservoirs from forming.

scholarly journals Quinolones for the Treatment ofNeisseria GonorrhoeaeandChlamydia Trachomatis

1993 ◽  
Vol 1 (2) ◽  
pp. 108-113 ◽  
Author(s):  
Sebastian Faro
Keyword(s):  
Urinary Tract ◽  
Soft Tissue ◽  
Chlamydia Trachomatis ◽  
Urinary Tract Infections ◽  
Single Agent ◽  
Moderate Activity ◽  
Sexually Transmitted ◽  
Tract Infections

The most commonly sexually transmitted bacteria areNeisseria gonorrhoeaeandChlamydia trachomatis.The quinolones ofloxacin and ciprofloxacin have been shown to have activity against both of these bacteria in vitro and in vivo. Ofloxacin is particularly well suited for the treatment ofN. gonorrhoeaeandC. trachomatiscervical infection, which can be considered the earliest manifestation of pelvic inflammatory disease (PID). Not only can ofloxacin be effectively used as a single agent, it is also useful in treating urinary tract infections caused by Enterobacteriaceae. Although it has moderate activity against anaerobes in general, ofloxacin does have activity against the anaerobes commonly isolated from female patients with soft tissue pelvic infections. Thus, ofloxacin has the potential for being utilized to treat early salpingitis.

scholarly journals Medicinal Plants with Anti-Trichomonas vaginalis Activity in Iran: A Systematic Review

2019 ◽  
Author(s):  
Hajar ZIAEI HEZARJARIBI ◽  
Najmeh NADEALI ◽  
Mahdi FAKHAR ◽  
Masoud SOOSARAEI
Keyword(s):  
Systematic Review ◽  
Medicinal Plants ◽  
Trichomonas Vaginalis ◽  
Scientific Information ◽  
Medicinal Herbs ◽  
In Vivo Studies ◽  
Eligibility Criteria ◽  
Sexually Transmitted

Background: Trichomoniasis, due to Trichomonas vaginalis, is one of the most common sexually transmitted parasitic diseases in the world such as Iran. This systematic review aimed to explore the studies evaluating the medicinal herbs with anti- T. vaginalis activity which used in Iran. Methods: Articles published in 4 Persian and 4 English databases were obtained between 2000 and 2015 including Google Scholar, PubMed, Science Direct, Scopus, Magiran, Barakatkns (formerly IranMedex), Elm net, and SID (Scientific Information Database). Studies out of Iran, studies on animal models and articles on other parasite species than T. vaginalis were excluded from this review. Results: Twenty-one articles including in vitro experiments, met our eligibility criteria. Thoroughly, 26 types of plants were examined against T. vaginalis. Medicinal herbs such as Artemisia, Zataria multiflora, and Lavandula angustifolia are remarkably effective on T. vaginalis. As such, use of other parts of these plants in different concentrations and timelines is recommended for future in vivo studies. Conclusion: The present systematic review provides comprehensive and useful information about Iranian medicinal plants with anti-T. vaginalis activity, which would be examined in the future experimental and clinical trials and herbal combination therapy.

scholarly journals Emergence of Nanotechnology to Fight HIV Sexual Transmission: The Trip of G2-S16 Polyanionic Carbosilane Dendrimer to Possible Pre-Clinical Trials

2020 ◽  
Vol 21 (24) ◽  
pp. 9403
Author(s):  
Ignacio Relaño-Rodríguez ◽  
Maria Ángeles Muñoz-Fernández
Keyword(s):  
Clinical Trials ◽  
Histopathological Examination ◽  
Early Stage ◽  
Sexual Transmission ◽  
Reaction Times ◽  
Vaginal Mucosa ◽  
Carbosilane Dendrimer ◽  
Anti Hiv

Development of new, safe, and effective microbicides to prevent human immunodeficiency virus HIV sexual transmission is needed. Unfortunately, most microbicides proved ineffective to prevent the risk of HIV-infection in clinical trials. We are working with G2-S16 polyanionic carbosilane dendrimer (PCD) as a new possible vaginal topical microbicide, based on its short reaction times, wide availability, high reproducibility, and quantitative yields of reaction. G2-S16 PCD exerts anti-HIV activity at an early stage of viral replication, by blocking gp120/CD4/CCR5 interaction, and providing a barrier against infection for long periods of time. G2-S16 PCD was stable at different pH values, as well as in the presence of seminal fluids. It maintained the anti-HIV activity against R5/X4 HIV over time, did not generate any type of drug resistance, and retained the anti-HIV effect when exposed to semen-enhanced viral infection. Importantly, G2-S16 PCD did not modify vaginal microbiota neither in vitro or in vivo. Histopathological examination did not show vaginal irritation, inflammation, lesions, or damage in the vaginal mucosa, after administration of G2-S16 PCD at different concentrations and times in female mice and rabbit animal models. Based on these promising data, G2-S16 PCD could become a good, safe, and readily available candidate to use as a topical vaginal microbicide against HIV.

Effect of bovine lactoferrin onChlamydia trachomatisinfection and inflammation

2017 ◽  
Vol 95 (1) ◽  
pp. 34-40 ◽  
Author(s):  
Rosa Sessa ◽  
Marisa Di Pietro ◽  
Simone Filardo ◽  
Alessia Bressan ◽  
Luigi Rosa ◽  
...  
Keyword(s):  
Acute Infection ◽  
Host Cells ◽  
Developmental Cycle ◽  
Bovine Lactoferrin ◽  
Bacterial Disease ◽  
Chronic Infections ◽  
Sexually Transmitted ◽  
Obligate Intracellular Pathogen

Chlamydia trachomatis is an obligate, intracellular pathogen responsible for the most common sexually transmitted bacterial disease worldwide, causing acute and chronic infections. The acute infection is susceptible to antibiotics, whereas the chronic one needs prolonged therapies, thus increasing the risk of developing antibiotic resistance. Novel alternative therapies are needed. The intracellular development of C. trachomatis requires essential nutrients, including iron. Iron-chelating drugs inhibit C. trachomatis developmental cycle. Lactoferrin (Lf), a pleiotropic iron binding glycoprotein, could be a promising candidate against C. trachomatis infection. Similarly to the efficacy against other intracellular pathogens, bovine Lf (bLf) could both interfere with C. trachomatis entry into epithelial cells and exert an anti-inflammatory activity. In vitro and in vivo effects of bLf against C. trachomatis infectious and inflammatory process has been investigated. BLf inhibits C. trachomatis entry into host cells when incubated with cell monolayers before or at the moment of the infection and down-regulates IL-6/IL-8 synthesized by infected cells. Six out of 7 pregnant women asymptomatically infected by C. trachomatis, after 30 days of bLf intravaginal administration, were negative for C. trachomatis and showed a decrease of cervical IL-6 levels. This is the first time that the bLf protective effect against C. trachomatis infection has been demonstrated.

scholarly journals Dendrimers, a New Class of Candidate Topical Microbicides with Activity against Herpes Simplex Virus Infection

2000 ◽  
Vol 44 (9) ◽  
pp. 2471-2474 ◽  
Author(s):  
N. Bourne ◽  
L. R. Stanberry ◽  
E. R. Kern ◽  
G. Holan ◽  
B. Matthews ◽  
...  
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Antiviral Activity ◽  
Rectal Mucosa ◽  
Biological Properties ◽  
Sexually Transmitted ◽  
Topical Microbicides ◽  
Simplex Virus

ABSTRACT Dendrimers are large highly branched macromolecules synthesized from a polyfunctional core. They have shown a variety of biological properties, including, in some instances, antiviral activity. In this study, five dendrimers were evaluated for in vitro activity against herpes simplex virus (HSV) types 1 and 2 by cytopathic effect (CPE) inhibition and plaque reduction (PR) assay in human foreskin fibroblast cells. All of the compounds were active against both virus types in the CPE inhibition assay, in which drug was added to the cells prior to the addition of virus. Antiviral activity was reduced or lost in the PR assays, in which the cells were incubated with the virus before the drug was added. The prophylactic efficacy suggested that the dendrimers might have potential as topical microbicides, products intended to be applied to the vaginal or rectal mucosa to protect against sexually transmitted infections. Three dendrimers were evaluated for this application against genital HSV infection in mice. Two of the compounds, BRI-2999 and BRI-6741, significantly reduced infection rates when 15 μl of a 100-mg/ml solution was administered immediately prior to intravaginal challenge, and the most effective compound, BRI-2999, provided significant protection even when applied 30 min before challenge. This is the first report of microbicidal activity by dendrimers in vivo.

scholarly journals In Vitro Microbicidal Activities of Cecropin Peptides D2A21 and D4E1 and Gel Formulations Containing 0.1 to 2% D2A21 against Chlamydia trachomatis

2002 ◽  
Vol 46 (1) ◽  
pp. 34-41 ◽  
Author(s):  
L. M. Ballweber ◽  
J. E. Jaynes ◽  
W. E. Stamm ◽  
M. F. Lampe
Keyword(s):  
Chlamydia Trachomatis ◽  
Initial Exposure ◽  
Sexually Transmitted ◽  
Ultrastructural Studies ◽  
Ph Values ◽  
Further Development ◽  
Gel Formulations ◽  
Powerful Strategy ◽  
Topical Microbicide

ABSTRACT Topically applied microbicides that eradicate pathogens at the time of initial exposure represent a powerful strategy for the prevention of sexually transmitted infections. To aid in the further development of an effective topical microbicide, we assessed the minimum cidal concentration (MCC) of two cecropin peptides, D2A21 and D4E1, and gel formulations containing 0.1 to 2% D2A21 against Chlamydia trachomatis in vitro. The MCC of peptide D2A21was 5 μM (18.32 μg/ml), and that of peptide D4E1 was 7.5 μM (21.69 μg/ml). The MCC of gel formulations containing 2% D2A21 was 0.2 mM (0.7 mg/ml), and that of gel formulations containing 0.5% D2A21 was 0.2 mM (0.7 mg/ml). There was no significant variation in the results when two different C. trachomatis strains were tested, and the addition of 10% human blood did not significantly alter the MCCs. pH values above and below 7 reduced the activity of the D2A21 peptide alone, but the MCC of the 2% D2A21 gel formulation was only slightly altered at the various pHs tested. Ultrastructural studies indicated that C. trachomatis membranes were disrupted after D2A21 exposure, resulting in leakage of the cytoplasmic contents. These in vitro results suggest that these cecropin peptides may be an effective topical microbicide against C. trachomatis and support the need for further evaluation.

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