Combined antifungal nanocarriers based on self-assembled nystatin and pillar[5]arene with a terpene moiety

In this study, nanocarriers based on self-assembled nystatin and pillar[5]arene were proposed. It was shown that pillar[5]arene with a terpene moiety is capable of targeted delivery of the natural antifungal drug nystatin to the cell membrane of opportunistic fungi (<i>Candida</i> sp.). A water-soluble pillar[5]arene containing a farnesyl moiety was synthesized for the first time. The membranotropic properties of the synthesized pillar[5]arene were demonstrated using the model lipid systems DPPC and DPPC : POPG. The formation of associates between pillar[5]arene and nystatin was confirmed by 2D DOSY, ¹H-¹H NOESY spectroscopy, and molecular dynamics. UV spectroscopy revealed that pillar[5]arene interacts with nystatin in a 1 : 2 stoichiometry. Dynamic light scattering and transmission electron microscopy showed that pillar[5]arene and nystatin form a stable monodisperse system with spherical-shaped associates. This study revealed that the pillar[5]arene/nystatin system exhibits more effective antifungal activity against clinical isolates of <i>Candida</i> sp. and <i>Saccharomyces cerevisiae</i> compared to free nystatin or pillar[5]arene. These findings represent a promising approach for the discovery of new membrane-targeting nanocarriers for the treatment of fungal diseases.