Synthesis of methotrexatum intercalated layered double hydroxides by different methods: Biodegradation process and bioassay explore

• The MTX/LDH hybrids were synthesized by four different routes.
• The anticancer effect of the hybrids is closely related with their monodispersity and regularity.
• The biodegradation process of MTX/LDH hybrids is explored emphatically to make out the mechanism of drug-release.

A series of methotrexatum intercalated layered double hydroxides (MTX/LDHs) hybrids were synthesized by four different routes, i.e., typical coprecipitation method, reverse-microemulsion approach, ion-exchange and mechanochemical–hydrothermal procedures, at the same synthesis condition. The resulting hybrids were then characterized by X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), transmission electron microscopy (TEM), atomic force microscope (AFM) and thermogravimetry (TG) testing. From XRD and FTIR analysis, MTX anions were successfully intercalated into LDH interlayers for all hybrids. TEM images reveal that the monodispersity of samples from coprecipitation and reverse-microemulsion methods was much better than that of the others. Importantly, the biodegradation process of MTX/LDH hybrids is also examined in phosphate buffer solution (PBS). The results show that the biodegradation procedure can be divided into three stages: the release of drug by ion-exchange, the subsequent destruction of LDH structure and then the complete disintegration of LDHs. At last, bioassay results give the evidence that MTX/LDH hybrids synthesized from coprecipitation method present the highest tumor suppression effect.