Combination Therapy of Clinically Approved Antifungal Drugs Is Enhanced by Conjugation with Silver Nanoparticles

  • Muhammad Asim Hussain
  • Dania Ahmed
  • Ayaz Anwar
  • Samina Perveen
  • Shakil Ahmed
  • Itrat Anis
  • Muhammad Raza Shah
  • Naveed Ahmed Khan
Original Article


Silver nanoparticles (SN) have been recently developed as a new class of antimicrobial agents against numerous pathogenic microorganisms. SN have also been used as efficient drug delivery systems and have been linked with increasing drug potency. Here, we demonstrated the enhanced antifungal efficacy of nystatin (NYT) and fluconazole (FLU) after conjugation with SN. The antifungal bioactivity of NYT- and FLU-coated SN was evaluated against Candida albicans ATCC 10231 and Aspergillus brasiliensis ATCC 16404 by the agar tube dilution method. The aim of this study was to determine and compare the antifungal efficacy of NYT and FLU with their SN and, finally, the combination of both nanoparticles as NYT-SN + FLU-SN against pathogenic fungi. The results indicated that all test samples showed a dose-dependent response against tested fungi. SN significantly enhanced the antifungal effects of NYT and FLU as compared to drugs alone. We observed a remarkable increase in the percent inhibition of both fungi (90–100%) when treated with a combination of both nanoparticles NYT-SN + FLU-SN at 200 μg/mL only. Furthermore, the morphological modifications occurred at the surface of fungal species were also analyzed by atomic force microscopy (AFM) and scanning electron microscopy (SEM). While tested against primary human cell line, all SN showed negligible cytotoxicity. Hence, these results suggest that the combination of SN with NYT and FLU may have clinical implications in the treatment of fungal infections. However, in vivo studies are needed before recommending the use of these nanoparticles safely in clinical situations.


Nystatin Fluconazole Silver nanoparticles Antifungal activity Combination therapy 



The authors acknowledge the Higher Education Commission of Pakistan, and the International Center for Chemical and Biological Sciences, Karachi, Pakistan, and Sunway University, Selangor, Malaysia, for their support.

Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no conflict of interest.


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Copyright information

© Springer Nature Switzerland AG 2018

Authors and Affiliations

  1. 1.Department of ChemistryUniversity of KarachiKarachiPakistan
  2. 2.International Center for Chemical and Biological Sciences, H.E.J. Research Institute of ChemistryUniversity of KarachiKarachiPakistan
  3. 3.Department of Biological Sciences, School of Science and TechnologySunway UniversitySubang JayaMalaysia

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