Singh Manmohan, Kazzaz Jina, Chesko James, Soenawan Elawati, Ugozzoli Mildred, Giuliani Marzia, Pizza Mariagrazia, Rappouli Rino, O'Hagan Derek T
Chiron Vaccines Research, Chiron Corporation, 4560 Horton Street, Emeryville, CA 94608, USA.
J Pharm Sci. 2004 Feb;93(2):273-82. doi: 10.1002/jps.10538.
The adsorption behavior of model proteins onto anionic poly(lactide-co-glycolide) (PLG) microparticles was evaluated. PLG microparticles were prepared by a w/o/w solvent evaporation process in the presence of the anionic surfactant dioctyl sodium sulfosuccinate (DSS). The effect of surfactant concentration and adsorption conditions on the adsorption efficiency and release rates in vitro was also studied. Subsequently, the microparticle formulation was tested to evaluate the efficacy of anionic microparticles as delivery systems for recombinant antigens from Neisseria meningitides type B (Men B), with and without CpG adjuvant. Protein (antigen) binding to anionic PLG microparticles was influenced by both electrostatic interaction and by other mechanisms, including hydrophobic attraction. The Men B antigens adsorbed efficiently onto anionic PLG microparticles and, following immunization in mice, induced potent enzyme-linked immunosorbent assay (ELISA) and serum bactericidal activity in comparison to alum-adsorbed formulations. These Men B antigens represent an attractive approach for vaccine development.
评估了模型蛋白在阴离子聚（丙交酯 - 乙交酯）（PLG）微粒上的吸附行为。PLG微粒是在阴离子表面活性剂磺基琥珀酸二辛酯钠（DSS）存在下通过w/o/w溶剂蒸发法制备的。还研究了表面活性剂浓度和吸附条件对体外吸附效率和释放速率的影响。随后，测试了微粒制剂，以评估阴离子微粒作为携带B型脑膜炎奈瑟菌（Men B）重组抗原的递送系统的功效，有无CpG佐剂。蛋白质（抗原）与阴离子PLG微粒的结合受静电相互作用和其他机制（包括疏水吸引）的影响。Men B抗原有效地吸附到阴离子PLG微粒上，并且在小鼠免疫后，与明矾吸附制剂相比，诱导了高效的酶联免疫吸附测定（ELISA）和血清杀菌活性。这些Men B抗原代表了一种有吸引力的疫苗开发方法。
