Ceña-Diez, RafaelMartin-Moreno, Albade la Mata, F JavierGomez-Ramirez, RafaelMuñoz, EduardoArdoy, ManuelMuñoz-Fernández, Mª Angeles2023-01-252023-01-252019Ceña-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;14:2371-2381http://hdl.handle.net/10668/13896HIV-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.enAttribution-NonCommercial 4.0 Internationalhttp://creativecommons.org/licenses/by-nc/4.0/G1-S4 dendrimerG2-S16 dendrimerHIV-1HSV-2Platycodin Dtopical microbicideAnimalsAnti-Infective AgentsCell ProliferationChlorocebus aethiopsContraceptive AgentsDendrimersFemaleHerpesvirus 2, HumanHumansLeukocytes, MononuclearMaleMice, Inbred BALB CSaponinsSilanesSperm CapacitationSpermatozoaToxicity TestsTriterpenesVaginaVero Cellsresearch article31040662open accessAnticonceptivosAntiinfecciososCapacitacion espermaticaLeucocitos mononuclearesProliferación celularPruebas de toxicidadDendrimeros10.2147/IJN.S1884951178-2013PMC6452809https://www.dovepress.com/getfile.php?fileID=48876https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6452809/pdf