Layered Double Hydroxides as a Drug Delivery Vehicle for S-Allyl-Mercapto-Cysteine (SAMC)

Abstract

The intercalations of anionic molecules and drugs in layered double hydroxides (LDHs) have been intensively investigated in recent years. Due to their properties, such as versatility in chemical composition, good biocompatibility, high density and protection of loaded drugs, LDHs seem very promising nanosized systems for drug delivery. In this work, we report the intercalation of S-allyl-mercapto-cysteine (SAMC), which is a component of garlic that is well-known for its anti-tumor properties, inside ZnAl-LDH (hereafter LDH) nanostructured crystals. In order to investigate the efficacy of the intercalation and drug delivery of SAMC, the intercalated compounds were characterized using X-ray powder diffraction (XRD), Fourier-transform infrared spectroscopy (FT-IR) and scanning electron microscopy (SEM). The increase in the interlayer distance of LDH from 8.9 Å, typical of the nitrate phase, to 13.9 Å indicated the intercalation of SAMC, which was also confirmed using FT-IR spectra. Indeed, compared to that of the pristine LDH precursor, the spectrum of LDH-SAMC was richly structured in the fingerprint region below 1300 cm−1, whose peaks corresponded to those of the functional groups in the SAMC molecular anion. The LDH-SAMC empirical formula, obtained from UV-Vis spectrophotometry and thermogravimetric analysis, was [Zn0.67Al0.33(OH)2]SAMC0.15(NO3)0.18·0.6H2O. The morphology of the sample was investigated using SEM: LDH-SAMC exhibited a more irregular size and shape of the flake-like crystals in comparison with the pristine LDH, with a reduction in the average crystallite size from 3 µm to about 2 µm. In vitro drug release studies were performed in a phosphate buffer solution at pH 7.2 and 37 °C and were analyzed using UV-Vis spectrophotometry. The SAMC release from LDH-SAMC was initially characterized by a burst effect in the first four hours, during which, 32% of the SAMC is released. Subsequently, the release percentage increased at a slower rate until 42% after 48 h; then it stabilized at 43% and remained constant for the remaining period of the investigation. The LDH-SAMC complex that was developed in this study showed the improved efficacy of the action of SAMC in reducing the invasive capacity of a human hepatoma cell line.