Hydrophobically modified alginate hydrogels as protein carriers with specific controlled release properties

Amphiphilic derivatives of sodium alginale, prepared by chemical covalent binding of long alkyl chains onto the polysaccharide backbone via ester functions, form strong hydrogels in aqueous solutions. The shear-thinning and thixotropic behaviors of these hydrogels have been exploited to prepare particles (millimetric beads or mickoparticles) by dispersion in sodium chloride solutions. This all-aqueous procedure was used for the encapsulation of model proteins, such as bovine serum albumin (BSA) and human hemoglobin (Hb), or of a vaccine protein (Helicobacterpylori (H. pylori) urease). In all cases, the encapsulation yields were very high (70-100%). No release of model proteins was observed in water within several days, in contrast with protein-loaded calcium alginate particles, which exhibit an important release within only a few hours. The controlled release of proteins can, however, be achieved by inducing the dissociation of the physical hydrophobic network. This dissociation has been obtained either by addition of surfactants, acting as disrupting agents of intermolecular hydrophobic junctions, or of esterases such as lipases, which hydrolyze the ester bond between alkyl chains and the polysaccharide backbone. The level of immunization against H. pylori infection in mice, induced by encapsulated urease administrated by either systemic or mucosal routes, was also assessed. (C) 2004 Published by Elsevier BX.