Rodríguez-Izquierdo, IgnacioSepulveda-Crespo, DanielLasso, Jose MaríaResino, SalvadorMuñoz-Fernández, María Ángeles2022-05-262022-05-262022-05Wiley Interdiscip Rev Nanomed Nanobiotechnol. 2022 May;14(3):e1774.http://hdl.handle.net/20.500.12105/14552Although a wide variety of topical microbicides provide promising in vitro and in vivo efficacy, most of them failed to prevent sexual transmission of human immunodeficiency virus type 1 (HIV-1) in human clinical trials. In vitro, ex vivo, and in vivo models must be optimized, considering the knowledge acquired from unsuccessful and successful clinical trials to improve the current gaps and the preclinical development protocols. To date, dendrimers are the only nanotool that has advanced to human clinical trials as topical microbicides to prevent HIV-1 transmission. This fact demonstrates the importance and the potential of these molecules as microbicides. Polyanionic dendrimers are highly branched nanocompounds with potent activity against HIV-1 that disturb HIV-1 entry. Herein, the most significant advancements in topical microbicide development, trying to mimic the real-life conditions as closely as possible, are discussed. This review also provides the preclinical assays that anionic dendrimers have passed as microbicides because they can improve current antiviral treatments' efficacy.engVoRHIV-1AcceptabilityDendrimerPreclinical stepsRegulationVaginal microbicideAttribution-NonCommercial-NoDerivatives 4.0 Internacional35018739143e177410.1002/wnan.17741939-0041Wiley Interdisciplinary Reviews. Nanomedicine and Nanobiotechnologyopen access