Breaking fungal biofilms and multidrug resistance using intelligent ciclopirox-based nanotechnology: Design and experimental validation

F. G. Ali; A. F. Abdullah; T. I. Qasim; H. H. Chasb

doi:10.15421/0226046

F. G. Ali University of Basrah
A. F. Abdullah University of Basrah
T. I. Qasim University of Basrah
H. H. Chasb University of Basrah

Keywords: Ciclopirox, CPX-NP, extracellular polymeric substance, Candida albicans.

Abstract

Fungal diseases and especially those linked to biofilms and multidrug resistance (MDR) are a growing health issue around the world, thus leading to the need to develop advanced methods of therapy. The standard antifungal treatment often does not have sufficient efficacy against such multifactorial problems. This study was intended to develop and test an intell i gent c iclopirox -based nanoplatform (CPX-NP) that would bypass mechanisms of MDR and interfere with fungal biofilms . CPX-NPs were produced by nanoprecipitation , and nanospheres with the best physicochemical properties (diameter less than 150 nm, low polydispersity , negative zeta potential) were obtained. Their action against MDR fungal isolates was investiga t ed in vitro , inclu d ing the establishment of the minimum inhibitory concentration (MIC), efflux pump inhibition, cytotoxicity tests, and biofilm penetration tests. CPX-NPs could selectively release c iclopirox in the acidic biofilm microenvironment leading to a decrease in MIC to a maximum of eight-fold compared to free c iclopirox . The nanoplatform also exhibited sup e rior biofilm penetration, strong efflux pumping and high therapeutic selectivity index (SI = 100) which are reflective of insi g nificant cytotoxicity of the human cell. The intelligent CPX-NP platform represents a viable and effective approach to the fight against the MDR fungi infe c tion and biofilm eradication, which will subsequently result in the development of safer and more effective antifungal therapies.

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