Rafati H, Lavelle E C, Coombes A G, Stolnik S, Holland J, Davis S S
Department of Pharmaceutical Sciences, University of Nottingham, UK.
Vaccine. 1997 Dec;15(17-18):1888-97. doi: 10.1016/s0264-410x(97)00134-5.
The effect of different surfactants on the surface characteristics of poly(D,L-lactideco-glycolide) microparticles prepared by the emulsification/solvent evaporation technique was investigated and the immune response to a protein antigen (OVA) associated with these microparticles was measured. Three surfactants--polyvinyl alcohol (PVA, a conventional stabilizer of PLG microparticles), the non-ionic surfactant, poly(oxyethylene glycerol mono-oleate) [Tagat] and Bile salts (a natural emulsifer)--were used to produce OVA-loaded PLG microparticles. Antigen was detected at the surface of all three types of OVA-loaded microparticles, in amounts in excess of 40% of the total protein load. The levels of specific serum IgG antibody elicited to OVA were significantly higher (P < 0.05) after a single subcutaneous administration of antigen associated with the Bile salts and Tagat formulations compared to the PVA formulation. A strong correlation was revealed between the levels of antibody measured and the magnitude of negative surface charge of the particulate carrier. The pattern of the IgG antibody response to OVA was similar in all three cases, indicating that the degradation rate of the PLG polymer determined the duration of the response. The results demonstrate the potential of using different surfactants to produce PLG microparticles with increased adjuvant activity.
研究了不同表面活性剂对通过乳化/溶剂蒸发技术制备的聚（D，L-丙交酯-乙交酯）微粒表面特性的影响，并测定了与这些微粒相关的蛋白质抗原（OVA）的免疫反应。使用三种表面活性剂——聚乙烯醇（PVA，PLG微粒的传统稳定剂）、非离子表面活性剂聚（氧乙烯甘油单油酸酯）[Tagat]和胆盐（一种天然乳化剂）——来制备负载OVA的PLG微粒。在所有三种负载OVA的微粒表面均检测到抗原，其含量超过总蛋白负载量的40%。与PVA制剂相比，单次皮下注射与胆盐和Tagat制剂相关的抗原后，引发的针对OVA的特异性血清IgG抗体水平显著更高（P<0.05）。所测抗体水平与颗粒载体负表面电荷的大小之间存在很强的相关性。在所有三种情况下，对OVA的IgG抗体反应模式相似，表明PLG聚合物的降解速率决定了反应的持续时间。结果证明了使用不同表面活性剂制备具有增强佐剂活性的PLG微粒的潜力。
