Controlled In Vitro Release of the Anticancer Drug Chlorogenic Acid Using Magnesium/Aluminium-Layered Double Hydroxide as a Nanomatrix

The anticancer agent chlorogenic acid was intercalated into 2D nanolamellae containing a Mg/Al-NO3-layered double hydroxide using direct (co-precipitation) and indirect (ion-exchange) techniques to form new nanocomposites called CMAC and CMAE, respectively. The loading of chlorogenic acid in the nanocomposites was estimated to be 37.3% for CMAE and 54.2% for CMAC; both nanocomposites show mesoporous properties. The basal spacings of CMAE and CMAC were expanded to 11.79 and 12.18 angstrom, respectively, compared to the host, suggesting that chlorogenates, or the anions of chlorogenic acid, were intercalated into the nanolamellae of Mg/Al-layered double hydroxides, arranging themselves in a horizontal monolayer at a 90 angle from the x-axis in CMAE and at a 50 angle for CMAC. The intercalation process was also confirmed using X-ray diffraction and Fourier transform infrared studies, and the intercalated chlorogenic acid was more thermally stable than free chlorogenic acid. The release of chlorogenate from the CMAE and CMAC in pH 7.4 and 4.8 phosphate buffer occurred in a controlled manner and was governed by a pseudo-second order release mechanism. The in vitro anti-cancer properties of both CMAE and CMAC against various human cancer cells including MCF-7, HeLa, HepG2, A549, and normal 3T3 fibroblast cells were investigated using a cell cytotoxicity assay. The CMAE and CMAC showed better cytotoxicity against cancer cells, particularly the HepG2 liver cancer cells, in a dose-dependent manner, and these nanocomposites did not produce any toxicity behavior in normal fibroblast cells. This preliminary investigation suggests that the nanocomposites showed anti-tumor properties against cancer cells without showing toxicity towards normal fibroblast cells; therefore, further pre-clinical studies must explore the potential of nanocomposites as an anticancer drug delivery system.