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Incorporation of 2-amino-thiophene derivative in nanoparticles: enhancement of antifungal activity

  • Clinical Microbiology - Research Paper
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Abstract

The objective of this study was to evaluate the effects of nanoparticles (nanospheres and nanocapsules) of the promising antifungal 2-amino-thiophene (6CN10) and 6CN10 complexed with 2-hydroxypropyl-β-cyclodextrin (6CN10:HP-β-CD) in vitro and compared with free drug against Candida and Cryptococcus, using a microdilution method to measure susceptibility. The Candida and Cryptococcus clinical strains were identified using phenotypic methods and matrix-assisted laser desorption/ionization-time of flight (MALDI-TOF). To measure in vitro antifungal susceptibility, we used microdilution trials. Serial drug or nanoparticle dilutions were prepared according to the CLSI M27-A3 guidelines. Anti-biofilm activity was verified for Cryptococcus neoformans. All Candida isolates were sensitive to the free drug (MIC = 41.66–333.33 μg/mL) and were able to grow even at the higher concentration tested for all 6CN10 nanoparticles. However, the Cryptococcus neoformans strains presented MIC values of 0.32–83.33 μg/mL for 6CN10 nanoparticles, and MIC values of 0.1–0.2 μg/mL for 6CN10:HP-β-CD nanoparticles, i.e., 3333 times more active than the free drug (MIC values 166.66–333.33 μg/mL), and presenting activity greater than that of the reference drug amphotericin B (MIC = 0.5–0.125 μg/mL). 6CN10:HP-β-CD nanosphere also showed high anti-biofilm potential. The in vitro study showed that the nanoparticles allowed better drug efficiency against Cryptococcus than did the free drug. These results suggest that 6CN10-loaded nanoparticles may become a future alternative for cryptococcosis and candidiasis therapy. In vivo experiments are essential prior to clinical use.

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Acknowledgments

The authors wish to thank the Fundação de Amparo à Ciência e Tecnologia de Pernambuco (FACEPE, Pernambuco, Brazil) for the scholarship of Giovanna R. A. Eleamen and the Diretoria de Inovação e Empreendedorismo (DINE/UFPE) for support funding by Edital de Apoio a Inovação 2014. We also would like to thank the Center for Strategic Technologies Northeastern (CETENE, Brazil) for MALDI-TOF MS, ZETATRAC, and SEM analyses and URM Culture Collection (UFPE, Brazil) for providing the isolates. This work was conducted during a scholarship of Wendell Wons Neves Financed by CAPES – Brazilian Federal Agency for Support and Evaluation of Graduate Education within the Ministry of Education of Brazil.

Funding

This work was financially supported by the Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq, Brazil) (grant numbers 455745/2014-5 and 308590/2017-1) and State University of Paraiba through the Research and Post-Graduation Program (PROPESQ/PRPGP). R. G. Lima-Neto is a researcher fellow of Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq, Grant 310822/2018-1).

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Correspondence to Reginaldo Gonçalves de Lima-Neto.

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The collection of the clinical samples from patients was approved by the Ethics Committee of the Centre of Health Sciences of the Federal University of Pernambuco under protocol 01847812.0.0000.5208.

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The authors declare that they have no conflict of interest.

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Responsible Editor: Luis Henrique Souza Guimaraes.

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Neves, W.W., Neves, R.P., Macêdo, D.P.C. et al. Incorporation of 2-amino-thiophene derivative in nanoparticles: enhancement of antifungal activity. Braz J Microbiol 51, 647–655 (2020). https://doi.org/10.1007/s42770-020-00248-7

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  • DOI: https://doi.org/10.1007/s42770-020-00248-7

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