Methotrexatum intercalated layered double hydroxides: Statistical design, mechanism explore and bioassay study

•Increasing NaOH solution gives rise to high drug-loading capacity.•Increasing the alkali solution leads to high layer charge and regular morphology.•The monodispersity has critical effect on the tumor suppression efficiency.

A series of methotrexatum intercalated layered double hydroxide (MTX/LDH for short) hybrids have been synthesized by a mechanochemical–hydrothermal method, the statistical experiments are planned and conducted to find out the critical factor influencing the physicochemical properties. Four variables, i.e., addition of NaOH solution, grinding duration, hydrothermal temperature and time, are chosen to play as the examined factors in the orthogonal design. Furthermore, three respective levels, i.e., high, medium and low levels, are conducted in the design. The resulting hybrids are then characterized by X-ray diffraction (XRD) patterns, transmission electron microscope (TEM) graphs and Zeta potentials. XRD diffractions indicate that MTX anions have been successfully intercalated into LDH interlayers and the amount of NaOH solution can change the gallery height greatly. The information from TEM graphs and Zeta potentials state that the increase of alkali solution gives rise to regular morphology and the increase of Zeta potentials. As a result of the statistical analysis, addition of alkali solution is the major factor affecting the morphology and drug-loading capacity. At last, the mechanism of particle growth is explored emphatically, and the anticancer efficacy of some MTX/LDH hybrids is estimated by MTT assay on A549 cells as well.

Graphical abstractSchematic illustration of synthesis and properties of MTX intercalated LDH hybrids.Figure optionsDownload full-size imageDownload as PowerPoint slide