Layered double hydroxide nanoparticles (LDHs) have shown the excellent capability and good adjuvant function as a nanocarrier for protein antigen delivery to enhance the immune response. Furthermore, LDHs have good biocompatibility and low cytotoxicity. However, their oral vaccine delivery efficiency is limited due to acidic/enzyme degradation in the stomach and low bioavailability in the small intestine. To overcome these challenges, alginate-chitosan coated LDHs nanocomposites (ALG-CHT-LDH) have been developed and used as a carrier for oral protein vaccine delivery. The physicochemical properties of ALG-CHT-LDH have been determined by dynamic light scattering (DLS), transmission electron microscopy (TEM), and ultraviolet visible (UV-Vis) spectroscopy. Protein release properties of LDHs with/without polymer coating have been investigated at various pHs. The protein release profile of ALG-CHT-LDH nanocomposites indicated that ALG-CHT coating could partially protect protein release at the acidic condition (pH 1.2). The cellular uptake efficiency of protein delivered by ALG-CHT-LDH for the intestine cells and macrophages were studied. After alginate layer falls from ALG-CHT-LDH nanocomposite, flow cytometry analysis (FACS) data suggest that chitosan-coated LDHs significantly enhance the internalization of proteins at the Caco2 and macrophage cells. (C) 2019 Elsevier Inc. All rights reserved.