Nystatin antifungal micellar systems on endotracheal tubes: Development, characterization and in vitro evaluation

Decontamination of patients’ clinical devices in intensive care units is generally performed with an antifungal suspension. Nystatin is a widely-used high spectrum antifungal due to its low systemic absorption. However, nystatin has high hydrophobicity which hinders the contact with the internal lumen of the devices. In this work, hydrophilic micellar systems of nystatin were developed with sodium deoxycholate on silicone endotracheal tubes. The physical characteristics of the micellar system at different nystatin:deoxycholate ratios were studied using scanning electron microscopy, X-ray powder diffraction and differential scanning calorimetry. The electron microscopy results reveal that the deoxycholate micellar system altered the surface morphology, and the size of the aggregates was observed to be smaller. The hydrophilic structures of deoxycholate produce systems with a high surface area containing nystatin molecules on their interior. The X-ray and differential scanning calorimetry assays revealed a typical change in the crystallinity of micellar systems when the deoxycholate proportion increases. The endothermic peak of nystatin was not observed in the micellar systems as a consequence of the reduced crystallinity. Nystatin was homogenously dispersed in the surfactant matrix. Micellar systems with 1:0.8 nystatin:deoxycholate ratio (MS-N:DC [1:0.8]) showed increased antifungal activity compared to nystatin raw material. Micellar systems also achieved an over 40% inhibition of Candida albicans biofilm formation. The results obtained in this study conclude that the higher hydrophilic characteristic of the surfactant deoxycholate enhances nystatin penetration into the surface of the endotracheal tubes.