School of Engineering, Center for Biomedical Engineering, Institute for Molecular and Nanoscale Innovation, Brown University, Providence, Rhode Island, USA.
Department of Chemistry, Brown University, Providence, Rhode Island, USA.
J Biomed Mater Res A. 2020 Nov 1;108(11):2263-2276. doi: 10.1002/jbm.a.36984. Epub 2020 Jun 12.
Fungal infections can cause significant patient morbidity and mortality. Nanoparticle therapeutics have the potential to improve treatment of these infections. Here we report the development of liposomal nanoparticles incorporating anidulafungin, a potent antifungal, with the goal of increasing its solubility and aiding in localization to fungi. Liposomes were fabricated with three concentrations of anidulafungin yielding monodisperse ~100 nm unilamellar vesicles. All three formulations inhibited planktonic Candida albicans growth at a minimum inhibitory concentration equivalent to free drug. All three formulations also disrupted preformed C. albicans biofilms, reducing fungal burden by as much as 99%, exhibiting superior biofilm disruption compared with free drug. Liposome formulations tested in vivo in C. albicans infected Galleria mellonella wax moth larvae demonstrated increased survival compared to free drug equivalents, leading to a survival of 33 to 67% of larvae over 7 days depending on the liposome utilized compared with only 25% survival of larvae administered free drug. Liposomal formulations along with free anidulafungin did not cause red blood cell lysis. Ultimately, the liposome formulations reported here increased anidulafungin solubility, displayed promising efficacy against planktonic and biofilm C. albicans, and improved the survival of C. albicans-infected G. mellonella compared to free anidulafungin.
真菌感染可导致患者发病率和死亡率显著增加。纳米颗粒疗法具有改善这些感染治疗的潜力。在这里，我们报告了载有那非那胺的脂质体纳米颗粒的开发，那非那胺是一种有效的抗真菌药物，旨在提高其溶解度并帮助其定位到真菌。脂质体采用三种浓度的那非那胺制备，得到单分散性~100nm 的单层囊泡。所有三种配方都能以相当于游离药物的最小抑菌浓度抑制浮游念珠菌的生长。所有三种配方还破坏了预先形成的白色念珠菌生物膜，使真菌负荷减少多达 99%，与游离药物相比，表现出更好的生物膜破坏作用。在感染白色念珠菌的大蜡螟幼虫体内进行的脂质体配方试验表明，与游离药物等效物相比，存活率有所提高，导致 7 天内 33%至 67%的幼虫存活，而给予游离药物的幼虫存活率仅为 25%。脂质体配方和游离那非那胺均不会导致红细胞裂解。最终，本文报道的脂质体配方提高了那非那胺的溶解度，对浮游和生物膜白色念珠菌显示出有希望的疗效，并提高了感染白色念珠菌的大蜡螟的存活率，优于游离那非那胺。
