Maryam Moazeni
1,2 , Majid Saeedi
3 , Hamidreza Kelidari
3 , Behrad Roohi
4, Mohammad T Hedayati
1,2 , Tahereh Shokohi
1,2 , Mojtaba Nabili
5 , Kofi Asare-Addo
6 , Ali Nokhodchi
7,8* 1 Invasive Fungi Research Center, Communicable Diseases Institute, Mazandaran University of Medical Sciences, Sari, Iran
2 Department of Medical Mycology, School of Medicine, Mazandaran University of Medical Sciences, Sari, Iran
3 Department of Pharmaceutics, Faculty of Pharmacy, Mazandaran University of Medical Sciences, Sari, Iran
4 Student Research Committee Center, Mazandaran University of Medical Sciences, Sari, Iran
5 Faculty of Medicine, Sari Branch, Islamic Azad University, Sari, Iran
6 Department of Pharmacy, University of Huddersfield, Queensgate, Huddersfield, HD1 3DH, UK
7 Pharmaceutics Research Laboratory, School of Life Sciences, University of Sussex, Arundel Building, Brighton BN1 9QJ, UK
8 Lupin Pharmaceutical Research Center, Coral Springs, Florida, USA
Abstract
Introduction: This study was proposed to assess the potential role of efflux transporters in reversing fluconazole resistance in Candida glabrata isolates treated with fluconazole loaded nanostructured lipid carriers (FLZ-NLCs).
Methods: The ultrasound technique was used to synthesize the FLZ-NLCs. Four fluconazole-resistant, as well as one susceptible standard C. glabrata isolates, were applied and exposed to FLZ/ FLZ-NLCs for 20 h at 37°C. Real-time PCRs were done to estimate the likely changes in ATP-binding cassette transporter genes.
Results: Similar to the FLZ-exposed-susceptible standard strain which showed no alteration, the genes were not up-regulated significantly under the FLZ-NLCs treated condition. While they were over-expressed when the yeasts were treated with fluconazole.
Conclusion: It is highly suggested that due to the nature of the NLCs which shields the whole conformation of the drug, FLZ is not recognized by the efflux transporter subunits and consequently the translocation would not happen.