Publication:
G1-S4 or G2-S16 carbosilane dendrimer in combination with Platycodin D as a promising vaginal microbicide candidate with contraceptive activity.

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Date

2019

Authors

Ceña-Diez, Rafael
Martin-Moreno, Alba
de la Mata, F Javier
Gomez-Ramirez, Rafael
Muñoz, Eduardo
Ardoy, Manuel
Muñoz-Fernández, Mª Angeles

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Dove Medical Press
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Abstract

HIV-1 and herpes simplex virus type-2 (HSV-2) represent two of the most relevant sexually transmitted diseases (STDs) worldwide. Moreover, each year there are >200 million pregnancies worldwide, and more than half are unintended. Continued high rates of unintended pregnancies and spread of HIV-1 and HSV-2 require new approaches to address these problems. G1-S4 and G2-S16 dendrimers emerge as potential candidates for the development of a topical microbicide due to their safety and effectivity against HIV-1 and HSV-2 infection, both in vitro and in vivo. Our goal is to develop a dual topical microbicide to prevent the transmission of STDs and unintended pregnancies. Platycodin D (PD) was selected for its great spermicidal activity, topical application, and biocompatibility. Toxicology and inhibitory profile of G1-S4/PD and G2-S16/PD were evaluated in vitro and in vivo. Spermicidal activity was assessed by a computer-assisted sperm analysis system (CASA). G1-S4/PD and G2-S16/PD presented >95% of HIV-1 inhibition in TZM-bl cells and peripheral blood mononuclear cells. CASA assessment determined that 0.25 mM of PD with therapeutic concentrations of G1-S4 or G2-S16 was able to induce 100% immobilization of the sperm in 30 seconds. To evaluate the toxicity in vivo, a vaginal toxicity assay was performed in BALB/c mice. No significant changes or damage to the vaginal epithelium after 7 consecutive days of application were observed. Our data indicate that G1-S4/PD and G2-S16/PD combinations are promising candidates to be developed for vaginal microbicides with contraceptive activity.

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MeSH Terms

Animals
Anti-Infective Agents
Cell Proliferation
Chlorocebus aethiops
Contraceptive Agents
Dendrimers
Female
Herpesvirus 2, Human
Humans
Leukocytes, Mononuclear
Male
Mice, Inbred BALB C
Saponins
Silanes
Sperm Capacitation
Spermatozoa
Toxicity Tests
Triterpenes
Vagina
Vero Cells

DeCS Terms

Anticonceptivos
Antiinfecciosos
Capacitacion espermatica
Leucocitos mononucleares
Proliferación celular
Pruebas de toxicidad
Dendrimeros

CIE Terms

Keywords

G1-S4 dendrimer, G2-S16 dendrimer, HIV-1, HSV-2, Platycodin D, topical microbicide

Citation

Ceña-Diez R, Martin-Moreno A, de la Mata FJ, Gómez-Ramirez R, Muñoz E, Ardoy M, et al. G1-S4 or G2-S16 carbosilane dendrimer in combination with Platycodin D as a promising vaginal microbicide candidate with contraceptive activity. Int J Nanomedicine. 2019 Apr 2;14:2371-2381