Effective drug delivery system based on hydrophobin and halloysite clay nanotubes for sustained release of doxorubicin

Abstract

Halloysite clay nanotubes (HNTs), which are natural nano-clays with a hollow tubular structure, have been widely studied for drug delivery and sustained release while largely limited by the complexity of surface modification. Hydrophobins are small surface-active proteins produced by filamentous fungi that self-assemble into nanolayers at hydrophobic/hydrophilic interfaces. In this study, hydrophobins including HGFI-his and a mutant MGF6-his were used as unique biomaterials to modify HNTs to construct drug delivery systems. Water contact angle and HNT dispersion assays demonstrated that MGF6-his performed better surface activity and rendered HNT more lasting stability than HGFI-his. MGF6-his-coated HNTs loaded with the anticancer drug doxorubicin hydrochloride ([email protected]) were further prepared and characterized by dynamic light scattering, fluorescence microscopy and transmission electron microscopy. This composite was found to form nanoparticles in size of 375.62 ± 17.85 nm and possess better dispersion stability owing to the coating of the MGF6-his. Excellent sustained release was observed at pH 3.3 and 5.0 but not at pH 7.4 in in vitro release assay. Moreover, an in vitro cytotoxicity assay showed that this system exhibited good bioactivity, killing about 70% of HeLa cells at a concentration of 150 μg/mL. Herein, the hydrophobin MGF6-his was designed as a novel approach for HNT surface modification, facilitating the dispersion and prolonging drug release simultaneously. These findings suggested that coating with hydrophobins has potential as a novel approach to develop HNT-based drug delivery systems.