Sepúlveda-Crespo Daniel, Gómez Rafael, De La Mata Francisco Javier, Jiménez José Luis, Muñoz-Fernández M Ángeles
Laboratorio InmunoBiología Molecular, IISGM, BioBank VIH HGM, CIBER-BBN, Madrid, Spain; Plataforma de Laboratorio, Hospital Gregorio Marañón, IISGM, BioBank VIH HGM, CIBER-BBN, Madrid, Spain.
Departamento de Química Inorgánica, Universidad de Alcalá, Campus Universitario, Alcalá de Henares, CIBER-BBN, Madrid, Spain.
Nanomedicine. 2015 Aug;11(6):1481-98. doi: 10.1016/j.nano.2015.03.008. Epub 2015 Mar 31.
Polyanionic carbosilane dendrimers (PCDs) are potential candidates for the development of new microbicides for the prevention of HIV transmission. Tenofovir (TFV), which has dual antiviral activity (anti-HIV/HSV-2), and maraviroc (MRV) are the most studied antiretrovirals as microbicides. Here, we introduce developments in the design of innovative dendrimer-based microbicides. We also review and discuss the combination of various PCDs with TFV and/or MRV for their anti-HIV-1 activity and synergistic combinatory potential. Well-defined combinations blocking HIV-1 infection in early steps of HIV-1 replication provide greater efficacy than monotherapy, as reflected by the decrease in concentration and increase in HIV-1 inhibition. These combinations are characterized by lower doses, which minimize toxic side-effects and the emergence of multi-drug resistant mutants. The above facts suggest that the combination of first- and second-generation PCDs with TFV and/or MRV represents a promising candidate microbicide for preventing HIV-1 sexual transmission and simultaneously suppressing HSV-2.
HIV infection remains a significant and unresolved problem for humankind, despite the development of combination antiretroviral therapy. It has been found that polyanionic carbosilane dendrimers have efficacy in preventing HIV transmission. In this comprehensive review article, the authors discuss the current status and latest development of the use of dendrimers in combination with other antiretroviral drugs as microbicides, which should stimulate others into further research in the fight against HIV.
聚阴离子碳硅烷树枝状大分子（PCD）是开发用于预防HIV传播的新型杀菌剂的潜在候选物。具有双重抗病毒活性（抗HIV/HSV-2）的替诺福韦（TFV）和马拉维罗（MRV）是作为杀菌剂研究最多的抗逆转录病毒药物。在此，我们介绍了基于树枝状大分子的创新杀菌剂设计的进展。我们还回顾并讨论了各种PCD与TFV和/或MRV组合的抗HIV-1活性及其协同组合潜力。在HIV-1复制早期阶段阻断HIV-1感染的明确组合比单一疗法具有更高的疗效，这体现在浓度降低和HIV-1抑制增加上。这些组合的特点是剂量较低，可将毒副作用和多药耐药突变体的出现降至最低。上述事实表明，第一代和第二代PCD与TFV和/或MRV的组合是预防HIV-1性传播并同时抑制HSV-2的有前景的候选杀菌剂。
尽管联合抗逆转录病毒疗法有所发展，但HIV感染对人类来说仍然是一个重大且未解决的问题。已发现聚阴离子碳硅烷树枝状大分子在预防HIV传播方面具有疗效。在这篇全面的综述文章中，作者讨论了树枝状大分子与其他抗逆转录病毒药物联合用作杀菌剂的现状和最新进展，这应会促使其他人在抗击HIV的斗争中进行进一步研究。
