The application of layered double hydroxide nanoparticles (LDHs) as potential anticancer drug delivery systems.
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Chemotherapy being one of the principle techniques used in cancer treatment, has been applied in the treatment of a wide spectrum of cancers. However, this mode of treatment is fraught with a myriad of challenges, reducing its effectivity and inducing the need for repeated treatments. Poor drug delivery systems or lack thereof, have led to patients suffering unpleasant side effects that not only cause collateral damage to their bodies but also reduces the quality of their lives. The current array of chemotherapeutic drugs available may be effective in certain cancers, nevertheless the need for their optimization is still necessary for better safety, stability and efficiency of treatment. Thus the current study was designed to investigate the potential of layered double hydroxide (LDH) nanoparticles in the delivery of the broad spectrum anticancer drug, 5-Fluorouracil (5-Fu). Four LDH nanoparticles, MgAl 2:1, MgAl 3:1, ZnAl 2:1and ZnAl 3:1 were successfully synthesized and intercalated with 5-Fu using the calcination reconstruction process to form nanohybrids. The LDHs and their nanohybrids, MgAl 2:1-5-Fu, MgAl 3:1-5-Fu, ZnAl 2:1-5-Fu and ZnAl 3:1-5-Fu were structurally confirmed using XRD, FTIR, UV-Vis, ICP-OES; with size, zeta potential and ultrastructural morphology investigated using nanoparticle tracking analysis (NTA) and electron microscopy (TEM and SEM). LDHs were characteristically hexagonal in shape with sizes ranging from 100 -150 nm, and high zeta potentials enforcing their colloidal stability. The successful intercalation of 5-Fu was confirmed from drug encapsulation efficiency studies to be between 40-60% in the respective LDHs. Furthermore, drug release studies revealed a steady controlled release of the drug over a 7-hour period at pH 4-7, with more than 60% of the drug being released by the end of this period. In vitro MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] and SRB (Sulphorhodamine B) cytotoxicity studies on free 5-Fu and LDH bound 5-Fu in human cell lines, breast adenocarcinoma cell line (MCF-7), hepatocellular carcinoma (HepG2), colorectal adenocarcinoma (CaCo-2) and embryonic kidney (HEK293), showed a dose dependent cytotoxicity profile with the free 5-Fu being more toxic to the cells than the bound drug. This was further confirmed in fluorescent apoptotic studies (dual acridine orange and ethidium bromide staining method), where free 5-Fu had a higher apoptotic index than the LDH bound 5-Fu