Antifungal Activity of Amphotericin B Conjugated to Carbon Nanotubes

被引:88
|
作者
Benincasa, Monica [2 ]
Pacor, Sabrina [2 ]
Wu, Wei [3 ]
Prato, Maurizio [1 ]
Bianco, Alberto [3 ]
Gennaro, Renato [2 ]
机构
[1] Univ Trieste, Dept Pharmaceut Sci, I-34127 Trieste, Italy
[2] Univ Trieste, Dept Life Sci, I-34127 Trieste, Italy
[3] CNRS, Inst Biol Mol & Cellulaire, Lab Immunol & Chim Therapeut, F-67084 Strasbourg, France
关键词
carbon nanotubes; functionalized carbon nanotubes; amphotericin B; antifungal activity; Candida spp; cytotoxicity; IN-VIVO; PULMONARY TOXICITY; KILLING KINETICS; CANDIDA; POSACONAZOLE; CASPOFUNGIN; RESISTANCE; THERAPY; VORICONAZOLE; FLUCONAZOLE;
D O I
10.1021/nn1023522
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
Amphotericin 8 (AMB) has long been considered the most effective drug in the treatment of: serious invasive fungal infections There are however, major limitations to its use due to several adverse effects, including acute infusional reactions and, most relevant, a dose-dependent nephrotoxicity. At least some of these effects are attributed to the aggregation of AMB as a result of its poor water solubility. To overcome this problem, reformulated versions of the drug have been developed, including a micellar dispersion of AMB With sodium deoxycholate (AMBD), its encapsulation into liposomes, or its incorporation into lipidic complexes. The development of nanobiotechnologies provides novel potential drug delivery systems that make use of nanomaterials such as functionalized carbon nanotubes (f-CNTs), which are emerging as an innovative and efficient tool for the transport and cellular translocation of therapeutic molecules. In this study, we prepared two conjugates between f-CNTs and AMB. The antifungal activity of these conjugates was tested against a; collection of reference and clinical fungal strains, In comparison to that of AMB alone or AMBD. Measured minimum inhibition concentration (MIC) values for f-CNT-AMB conjugates were either comparable to or better than those displayed by AMB and AMBD. Furthermore, AMBD-resistant Candida strains were found to be susceptible to f- CNT-AMB 1. Additional studies, aimed at Understanding the mechanism of action of the conjugates, suggest nonlytic mechanism, since the compounds show a major permeabilizing effect on the tested fungal strains only. after extended incubation. Interestingly, the f-CNT-AMB 1 does not show any significant toxic effect on Jurkat cells at antifungal concentrations.
引用
收藏
页码:199 / 208
页数:10
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