Facile synthesis of methotrexate intercalated layered double hydroxides: Particle control, structure and bioassay explore

•The particle size can be precisely controlled between 90 and 140 nm.•Different dropping ways can affect the morphology greatly.•Larger particles are more efficient in the suppression of the tumor cells.•Longer time treatment will weaken the bond between the MTX and LDH layers.

To study the influence of particle size on drug efficacy and other properties, a series of methotrexate intercalated layered double hydroxides (MTX/LDHs) were synthesized through the traditional coprecipitation method, using a mixture of water and polyethylene glycol (PEG-400) as the solvent. To adjust the particle size of MTX/LDHs, the dropping way, the volume ratio of water to PEG-400 and different hydrothermal treatment time changed accordingly, and the results indicate that the particle size can be controlled between 90 and 140 nm. Elemental C/H/N and inductive coupled plasma (ICP) analysis indicated that different synthesis conditions almost have no effect on the compositions of the nanohybrids. X-ray diffraction (XRD) patterns manifested the successful intercalation of MTX anions into the LDH interlayers, and it's also found out that different volume ratios of water to PEG-400 and variable dropping way can affect the crystallinity of the final samples, i.e., the volume ratio of 3:1 and pH decreasing are proved to be optimum conditions. Furthermore, both antiparallel monolayer and bilayers adopting different orientations are suggested for four samples from XRD results. Fourier transform infrared spectroscopy (FTIR) investigations proved the coexistence of CO32− and MTX anions in the interlayer of the nanohybrids. MTX/LDH particles exhibited hexagonal platelet morphology with round corner and different dropping  ways can affect the morphology greatly. Moreover, a DSC study indicated that longer time treatment can weaken the bond between the MTX anions and LDH layers. The kinetic release profiles told us that larger MTX/LDH particles have enhanced the ability of LDH layers to protect interlayer molecules. At last, the bioassay study indicated that the nanohybrids with larger diameters have higher tumor suppression efficiency.

Graphical abstractA series of methotrexate intercalated layered double hydroxides were synthesized by changing the dropping way, volume ratio of PEG-400 to water and hydrothermal treatment time and the release mechanism and the bioassay tests had been systematically investigated. Our study indicated that nanohybrids with larger diameters have higher tumor suppression efficiency.Figure optionsDownload full-size imageDownload as PowerPoint slide