Antifungal Activity of Amphotericin B Conjugated to Carbon Nanotubes
详细信息 查看全文
- 作者：Monica Benincasa ; Sabrina Pacor ; Wei Wu ; Maurizio Prato ; Alberto Bianco ; Renato Gennaro
- 刊名：ACS Nano
- 出版年：2011
- 出版时间：January 25, 2011
- 年：2011
- 卷：5
- 期：1
- 页码：199-208
- 全文大小：464K
- 年卷期：0
- ISSN：1936-086X
文摘
Amphotericin B (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 a 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.