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

Abstract

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 Å in pristine CaAl-LDH bilayered structure to 18.26 Å 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 Å in pristine LDH to 18.31 Å 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°C as compared with 290°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.