Zydowsky Thomas M
Population Council, HIV/AIDS Program, New York, New York 10065-6307, USA.
Curr Opin HIV AIDS. 2008 Sep;3(5):548-53. doi: 10.1097/COH.0b013e32830ab9dd.
To highlight promising areas of research and preview future generations of microbicides, this review will focus on reports that described new cellular or viral targets, drug substances, or strategies that are specifically intended for topical microbicides. Those reports that dealt with the design, discovery, and synthesis of anti-HIV agents for use in oral or parenteral formulations, while important for the microbicide field, are beyond the scope of this review.
Drug substances intended for topical microbicides are becoming increasingly target specific and, structurally, more complex. New production methods might reduce the cost of microbicides that contain these complex molecules. Genetically engineered probiotic vaginal bacteria express an even wider range of antiviral compounds, perhaps resulting in uninterrupted, coitally independent protection. Combination microbicides that contain two or more drug substances frequently act synergistically. The discovery of new cellular targets such as syndecan-3 might lead to more effective microbicides.
Future generations of microbicides will likely contain one or more complex or highly specific drug substances, resulting in safer and more effective products. Since compliance issues continue to confound HIV and herpes simplex virus trials, efforts to bring practical, coitally independent microbicides to developing countries will become a top priority.
为突出有前景的研究领域并展望下一代杀微生物剂,本综述将聚焦于描述新的细胞或病毒靶点、药物实体或专门用于局部用杀微生物剂的策略的报告。那些涉及用于口服或肠胃外制剂的抗HIV药物的设计、发现和合成的报告,虽然对杀微生物剂领域很重要,但不在本综述范围内。
用于局部用杀微生物剂的药物实体越来越具有靶点特异性,并且在结构上更加复杂。新的生产方法可能会降低含有这些复杂分子的杀微生物剂的成本。基因工程改造的益生菌阴道细菌可表达范围更广的抗病毒化合物,这可能会带来持续的、与性行为无关的保护。含有两种或更多种药物实体的复方杀微生物剂常常具有协同作用。新细胞靶点(如Syndecan-3)的发现可能会带来更有效的杀微生物剂。
下一代杀微生物剂可能会含有一种或多种复杂或高度特异性的药物实体,从而产生更安全、更有效的产品。由于依从性问题继续困扰着HIV和单纯疱疹病毒试验,将实用的、与性行为无关的杀微生物剂引入发展中国家的努力将成为首要任务。