G1-S4 or G2-S16 carbosilan dendrimer in combination with Platycodin D as a promising vaginal microbicide candidate with contraceptive activity
Received 24 September 2018
Accepted for publication 19 December 2018
Published 2 April 2019 Volume 2019:14 Pages 2371—2381
Checked for plagiarism Yes
Review by Single anonymous peer review
Peer reviewer comments 2
Editor who approved publication: Prof. Dr. Thomas J. Webster
Rafael Ceña-Diez,1,2 Alba Martin-Moreno,1 F Javier de la Mata,2,3 Rafael Gómez-Ramirez,2,3 Eduardo Muñoz,4 Manuel Ardoy,5 Ma Ángeles Muñoz-Fernández1,2
1Immunology Section, Head Inmuno-Biology Molecular Laboratory, Gregorio Marañón University General Hospital, Gregorio Marañón Health Research Institute (IiSGM), Spanish HIV HGM BioBank, Madrid, Spain; 2Networking Research Center on Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Madrid, Spain; 3Organic and Inorganic Chemistry Department, Alcalá University, Alcalá de Henares, Spain; 4Department of Cell Biology, Physiology and Immunology, Instituto Maimónides de Investigación Biomédicas de Córdoba (IMIBIC), Reina Sofía University Hospital, University of Córdoba, Córdoba, Spain; 5Human Reproduction Unit, Gregorio Marañon University General Hospital, Madrid, Spain
Purpose: 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.
Materials and methods: 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).
Results: 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.
Conclusion: Our data indicate that G1-S4/PD and G2-S16/PD combinations are promising candidates to be developed for vaginal microbicides with contraceptive activity.
Keywords: topical microbicide, HIV-1, HSV-2, Platycodin D, G1-S4 dendrimer, G2-S16 dendrimer
This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution - Non Commercial (unported, v3.0) License. By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms.Download Article [PDF] View Full Text [HTML][Machine readable]