Hydrophobically modified alginate hydrogels as protein carriers with specific controlled release properties.
Amphiphilic derivatives of sodium alginate, 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 microparticles) 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 (Helicobacter pylori (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.
Laboratoire de Chimie Physique Macromoléculaire, Groupe ENSIC, BP 451, UMR CNRS-INPL 7568, 54001 Nancy Cedex, France. Michele.Leonard@ensic.inpl-nancy.fr
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M
Leonard
M Rastello
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De Boisseson
P
P
Hubert
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F
Dalençon
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E
Dellacherie
D000464:Alginates / Q000737:chemistry*; D000818:Animals; D001428:Bacterial Vaccines / Q000276:immunology; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D003692:Delayed-Action Preparations; D004337:Drug Carriers / Q000737:chemistry*; D004339:Drug Compounding; D016650:Fluorescein-5-isothiocyanate; D016480:Helicobacter pylori / Q000276:immunology; D006454:Hemoglobins / Q000276:immunology; D020100:Hydrogels / Q000737:chemistry*; D006863:Hydrogen-Ion Concentration; D007114:Immunization; D007115:Immunization Schedule; D007074:Immunoglobulin G / Q000096:biosynthesis; D051379:Mice; D008863:Microspheres; D010316:Particle Size; D011506:Proteins / Q000008:administration & dosage* / Q000493:pharmacokinetics; D012710:Serum Albumin, Bovine / Q000737:chemistry; D014510:Urease / Q000276:immunology
D000464:Alginates; D001428:Bacterial Vaccines; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D006454:Hemoglobins; D020100:Hydrogels; D007074:Immunoglobulin G; D011506:Proteins; D012710:Serum Albumin, Bovine; D014510:Urease; D016650:Fluorescein-5-isothiocyanate