Leonard M, De Boisseson M Rastello, Hubert P, Dalençon F, Dellacherie E
Laboratoire de Chimie Physique Macromoléculaire, Groupe ENSIC, BP 451, UMR CNRS-INPL 7568, 54001 Nancy Cedex, France.
J Control Release. 2004 Aug 27;98(3):395-405. doi: 10.1016/j.jconrel.2004.05.009.
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.
海藻酸钠的两亲性衍生物是通过长烷基链经酯官能团与多糖主链进行化学共价结合制备而成的，它们在水溶液中形成强水凝胶。这些水凝胶的剪切变稀和触变行为已被用于通过分散在氯化钠溶液中来制备颗粒（毫米级珠子或微粒）。这种全水性方法用于包封模型蛋白，如牛血清白蛋白（BSA）和人血红蛋白（Hb），或一种疫苗蛋白（幽门螺杆菌脲酶）。在所有情况下，包封率都非常高（70 - 100%）。与负载蛋白质的海藻酸钙颗粒不同，后者在短短几小时内就会有大量释放，而在数天内未观察到模型蛋白在水中有释放。然而，蛋白质的控释可以通过诱导物理疏水网络的解离来实现。这种解离可以通过添加作为分子间疏水连接破坏剂的表面活性剂，或通过水解烷基链与多糖主链之间酯键的酯酶（如脂肪酶）来实现。还评估了通过全身或黏膜途径给予包封脲酶诱导的小鼠抗幽门螺杆菌感染的免疫水平。
