Chair and Department of Chemical Technology of Drugs, Poznan University of Medical Sciences, Grunwaldzka 6, 60-780 Poznań, Poland.
Chair and Department of Genetics and Pharmaceutical Microbiology, Poznan University of Medical Sciences, Swiecickiego 4, 60-781 Poznań, Poland.
J Control Release. 2021 Feb 10;330:599-617. doi: 10.1016/j.jconrel.2020.12.021. Epub 2020 Dec 24.
Fungal based diseases currently affect nearly a quarter of the population around the world, which diseases are usually limited to superficial infections. Perversely, along with the development of modern medicine, cases of life-threatening systemic fungi are more and more often encountered. Compared to antibacterial drugs, significantly fewer fungicides are tested and introduced to clinical practice. At the same time, the drug resistance of pathological fungi is constantly growing. In addition to obtaining new derivatives of already-established classes of drugs, such as azoles, there is a growing interest in new compounds with potentially new mechanisms and application possibilities. Polymers are included in the flow of these studies, and among them - dendrimers. Dendrimers are a special type of polymers with a strictly defined structure and a plethora of functionalization possibilities. This allows them to not only be used as effective antifungal drug carriers but also enables them to exhibit antifungal activity per se. In this review, we have introduced to the epidemiology of fungal infections and summarized the aspects related to their control and therapy. Various polymers and dendrimers with antifungal activity were presented. In the subsequent sections antifungal acting dendrimers were discussed within three subchapters, based on their chemical structure: (i) amino acid-based dendrimers, (ii) amino based dendrimers, and (iii) other, which do not share similarities in structure. We have gathered and summarized the reports regarding the direct action of dendrimers on infectious fungi, as well as their effect when used as solubilizers, carriers or adjuvants with currently used antifungals. Use of dendrimers for the sensing of fungi or their metabolites are also considered. Special attention was also paid to the applications of dendrimers together with photosensitizers in antimicrobial photodynamic therapy.
目前,全球近四分之一的人口受到真菌病的影响,这些疾病通常局限于浅表感染。但反常的是,随着现代医学的发展,越来越多地遇到危及生命的系统性真菌感染病例。与抗菌药物相比,经过测试并引入临床实践的杀真菌剂要少得多。同时,致病真菌的耐药性也在不断增强。除了获得已建立的唑类药物等类别的新衍生物外,人们对具有潜在新机制和应用可能性的新型化合物越来越感兴趣。聚合物也被纳入了这些研究的范畴,其中就包括树状聚合物。树状聚合物是一种特殊类型的聚合物,具有严格定义的结构和大量的功能化可能性。这不仅使它们能够用作有效的抗真菌药物载体,而且还使它们本身具有抗真菌活性。在这篇综述中,我们介绍了真菌病的流行病学,并总结了与它们的控制和治疗相关的方面。介绍了具有抗真菌活性的各种聚合物和树状聚合物。在随后的章节中,根据它们的化学结构,将具有抗真菌作用的树状聚合物分为三个子章节进行了讨论:(i)基于氨基酸的树状聚合物,(ii)基于氨基的树状聚合物,和(iii)其他结构上不相似的树状聚合物。我们收集并总结了关于树状聚合物对感染真菌的直接作用以及将其用作目前使用的抗真菌药物的增溶剂、载体或佐剂的效果的报告。还考虑了树状聚合物用于真菌或其代谢物检测的应用。特别关注了树状聚合物与光敏剂一起在抗菌光动力疗法中的应用。