Effect of trehalose on structural state of bovine serum albumin adsorbed onto mesoporous silica and the protein release kinetics in vitro

Abstract

Protein – silica composites are promising platform for development of novel formulations of protein drugs with improved pharmacological and consumer properties. Adsorption is simple and frequently used method of preparation of the composites. However often proteins undergo significant conformation changes upon interaction with silica surface leading to decrease or loss of their biological functionality. The aim of this study was to elucidate the ability of disaccharide trehalose to protect structure of bovine serum albumin (BSA) as model protein drug from unfolding in the protein – silica composites prepared by adsorption as well as an effect of the disaccharide on release kinetics of the protein from the composites. For this purpose, BSA was adsorbed onto presinthesized mesoporous silica from solutions containing trehalose and without it. The adsorbent was thoroughly characterized by X-ray diffraction, nitrogen adsorption/desorption, FTIR spectroscopy, dynamic light scattering. The influence of different amounts of trehalose on the protein loading, structural alterations of BSA in solutions and in the composites was studied. The protein release behavior from the composites was analyzed in vitro. It was found that trehalose promotes a higher protein loading in mesoporous silica, stabilization of BSA structure in the solid BSA- silica composites and the protein structure released from the composites. Trehalose also promotes a higher release rate of the protein from the synthesized composites. The effects increase with increasing amount of the disaccharide in the adsorption medium. Thus, use of trehalose can help to prepare high loaded BSA-silica composite with minimal structural alteration of the protein by adsorption and to regulate the protein release rate.