UniSA Clinical and Health Sciences, University of South Australia, Adelaide, SA, 5000, Australia.
Basil Hetzel Institute for Translational Health Research, Woodville South, Woodville, SA, 5011, Australia.
Drug Deliv Transl Res. 2021 Aug;11(4):1586-1597. doi: 10.1007/s13346-021-00943-4. Epub 2021 Mar 13.
Infections caused by fungal biofilms with rapidly evolving resistance against the available antifungal agents are difficult to manage. These difficulties demand new strategies for effective eradication of biofilms from both biological and inert surfaces. In this study, polymeric micelles comprised of di-block polymer, poly-(ethylene glycol) methyl ether methacrylate and poly 2-(N,N-diethylamino) ethyl methacrylate polymer, P(PEGMA-b-DEAEMA), were observed to exhibit remarkable inhibitory effects on hyphal growth of Candida albicans (C. albicans) and C. tropicalis, thus preventing biofilm formation and removing existing biofilms. P(PEGMA-b-DEAEMA) micelles showed biofilm removal efficacy of > 40% and a 1.4-log reduction in cell viability of C. albicans in its single-species biofilms. In addition, micelles alone promoted high removal percentage in a mixed biofilm of C. albicans and C. tropicalis (~ 70%) and remarkably reduced cell viability of both strains. Co-delivery of fluconazole (Flu) and amphotericin B (AmB) with micelles showed synergistic effects on C. albicans biofilms (3-log reduction for AmB and 2.2-log reduction for Flu). Similar effects were noted on C. albicans planktonic cells when treated with the micellar system combined with AmB but not with Flu. Moreover, micelle-drug combinations showed an enhancement in the antibiofilm activity of Flu and AmB against dual-species biofilms. Furthermore, in vivo studies using Caenorhabditis elegans nematodes revealed no obvious toxicity of the micelles. Targeting morphologic transitions provides a new strategy for defeating fungal biofilms of polymorphic resistance strains and can be potentially used in counteracting Candida virulence.
由对抗真菌药物迅速产生耐药性的真菌生物膜引起的感染难以治疗。这些困难需要新的策略来有效清除生物膜，包括从生物和惰性表面。在这项研究中，观察到由二嵌段聚合物、聚（乙二醇）甲基醚甲基丙烯酸酯和聚 2-（N，N-二乙基氨基）乙基甲基丙烯酸酯聚合物组成的聚合物胶束对白色念珠菌（C. albicans）和热带念珠菌（C. tropicalis）的菌丝生长表现出显著的抑制作用，从而阻止生物膜的形成并去除现有的生物膜。P(PEGMA-b-DEAEMA)胶束对其单种生物膜中的 C. albicans 显示出超过 40%的生物膜去除效力和 1.4 对数减少的细胞活力。此外，胶束本身在 C. albicans 和 C. tropicalis 的混合生物膜中促进了高去除百分比（~70%），并显著降低了两种菌株的细胞活力。与胶束共递送氟康唑（Flu）和两性霉素 B（AmB）对 C. albicans 生物膜显示出协同作用（AmB 降低 3 对数，Flu 降低 2.2 对数）。当用包含 AmB 的胶束系统处理时，对 C. albicans 浮游细胞也观察到类似的效果，但用 Flu 处理则没有。此外，胶束-药物组合增强了 Flu 和 AmB 对双种生物膜的抗生物膜活性。此外，使用秀丽隐杆线虫的体内研究表明胶束没有明显的毒性。针对形态转变提供了一种击败多态性耐药菌株真菌生物膜的新策略，可潜在用于对抗念珠菌的毒力。
