One-pot synthesis of CaAl-layered double hydroxide–methotrexate nanohybrid for anticancer application

One-pot (co-precipitation) synthesis route was employed for the first time to synthesize pristine CaAl-layered double hydroxide (LDH) and in-situ intercalation of the anticancer drug methotrexate (MTX) to prepare CaAl-LDH–MTX nanohybrid. An increase in the interplanar spacing of the (003) plane from 8.6 A in pristine CaAl-LDH bilayered structure to 18.26 A in CaAl-LDH–MTX nanohybrid indicated successful intercalation of anionic MTX into the interlayer space of CaAl-LDH. This was supported by the transmission electron micrographs, which showed an increase in average interlayer spacing from 8.7 A in pristine LDH to 18.31 A in LDH–MTX nanohybrid. Particle size and morphology analysis of pristine CaAl-LDH and LDH–MTX nanohybrid using both dynamic light scattering (DLS) technique and transmission electron microscopy (TEM) indicated a decrease in average particle size in LDH–MTX nanohybrid as compared with that of pristine LDH. Thermogravimetric analyses (TGA) revealed an enhancement in decomposition temperature of MTX bound to CaAl-LDH nanohybrid to $$380{^\circ }\hbox {C}$$ as compared with $$290{^\circ }\hbox {C}$$ in pure MTX molecule, indicating enhanced thermal stability, which supports stable electrostatic interaction of MTX within the interlayer position of LDH. CHN (carbon hydrogen nitrogen) analysis revealed nearly 49 wt% of MTX loading into CaAl-LDH, which closely matched with the result obtained from TGA of the nanohybrid. Cumulative release of MTX from CaAl-LDH–MTX in phosphate buffer solution showed a non-linear dependence with incubation time. Release mechanism of MTX from LDH–MTX nanohybrid was governed by diffusion mechanism at physiological pH of 7.4. The in vitro cytotoxicity study of LDH–MTX nanohybrid using MG-63 human osteosarcoma cell line indicated enhanced inhibition of the cancer cell proliferation compared with the MTX drug alone.