Cui Zhengrong, Mumper Russell J
Division of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, Lexington, KY 40536-0082, USA.
Int J Pharm. 2002 May 15;238(1-2):229-39. doi: 10.1016/s0378-5173(02)00079-0.
A significant emphasis has been placed on the development of improved adjuvants and delivery systems to improve both antibody production and cell-mediated immunity. The overall goal of this project was to cationize a model protein antigen, beta-galactosidase (nGal), coat the cationized Gal (cGal) on the surface of novel anionic nanoparticles engineered from microemulsion precursors, and assess the immune response of this system after subcutaneous injection to mice. Gal was chemically cationized as evidenced by gel electrophoresis. The cGal was coated on anionic nanoparticles (78+/-11 nm) engineered from oil-in-water microemulsion precursors to produce cGal-coated nanoparticles. The immune response to nGal with 'Alum', cGal alone, and cGal-coated nanoparticles were assessed after subcutaneous injection to Balb/c mice. cGal alone elicited similar antibody titer to nGal with 'Alum'. However, cGal-coated nanoparticles elicited the strongest and most reproducible antibody titer. cGal alone produced very high levels of Th1 cytokines, but low levels of Th2 cytokines. In contrast, cGal-coated nanoparticles significantly enhanced both the Th1 and Th2 cytokines. The results demonstrated the utility of antigen-coated nanoparticles to enhance both the humoral and Th1-type immune responses, in parallel.
人们一直非常重视开发改良佐剂和递送系统，以提高抗体产生和细胞介导的免疫。该项目的总体目标是将模型蛋白抗原β-半乳糖苷酶（nGal）阳离子化，将阳离子化的Gal（cGal）包被在由微乳液前体制备的新型阴离子纳米颗粒表面，并在皮下注射给小鼠后评估该系统的免疫反应。凝胶电泳证明Gal已被化学阳离子化。将cGal包被在由水包油微乳液前体制备的阴离子纳米颗粒（78±11nm）上，以生产cGal包被的纳米颗粒。在向Balb/c小鼠皮下注射后，评估了对nGal与“明矾”、单独的cGal以及cGal包被的纳米颗粒的免疫反应。单独的cGal引发的抗体滴度与nGal加“明矾”相似。然而，cGal包被的纳米颗粒引发了最强且最可重复的抗体滴度。单独的cGal产生非常高水平的Th1细胞因子，但Th2细胞因子水平较低。相比之下，cGal包被的纳米颗粒显著增强了Th1和Th2细胞因子。结果表明，抗原包被的纳米颗粒可同时增强体液免疫和Th1型免疫反应。
