The in vitro sustained release profile and antitumor effect of etoposide-layered double hydroxide nanohybrids

Lili Qin,¹ Mei Wang,² Rongrong Zhu,³ Songhui You,¹ Ping Zhou,¹ Shilong Wang<sup>3

1</sup>Department of Physical Education, Tongji University, Shanghai, People's Republic of China; ²Department of Chemistry, Tongji University, Shanghai, People's Republic of China; ³School of Life Science and Technology, Tongji University, Shanghai, People's Republic of China


Abstract: Magnesium-aluminum layered double hydroxides intercalated with antitumor drug etoposide (VP16) were prepared for the first time using a two-step procedure. The X-ray powder diffraction data suggested the intercalation of VP16 into layers with the increased basal spacing from 0.84–1.18 nm was successful. Then, it was characterized by X-ray powder diffraction, Fourier transform infrared spectroscopy, thermogravimetry and differential thermal analysis, and transmission electron microscopy. The prepared nanoparticles, VP16-LDH, showed an average diameter of 62.5 nm with a zeta potential of 20.5 mV. Evaluation of the buffering effect of VP16-LDH indicated that the nanohybrids were ideal for administration of the drugs that treat human stomach irritation. The loading amount of intercalated VP16 was 21.94% and possessed a profile of sustained release. The mechanism of VP16-LDH release in the phosphate buffered saline solution at pH 7.4 is likely controlled by the diffusion of VP16 anions from inside to the surface of LDH particles. The in vitro cytotoxicity and antitumor assays indicated that VP16-LDH hybrids were less toxic to GES-1 cells while exhibiting better antitumor efficacy on MKN45 and SGC-7901 cells. These results imply that VP16-LDH is a potential antitumor drug for a broad range of gastric cancer therapeutic applications.

Keywords: layered double hydroxides, etoposide, drug delivery, antitumor effect, sustained release