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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Identifiers
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
Advisors
Journal Title
Journal ISSN
Volume Title
Publisher
Dove Medical Press
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.
Description
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
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
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