School of Pharmacy, CHIRI, Western Australia Biomedical Research Institute, Curtin University, Perth, Western Australia 6845, Australia.
J Pharm Sci. 2012 Jan;101(1):233-44. doi: 10.1002/jps.22763. Epub 2011 Sep 22.
The objective of the present study was to evaluate immunological activities of chitosan-dextran sulfate (CS-DS) nanoparticle formulation of pertussis toxoid (PTXd) and its combination with a potential immunological adjuvant, immunoglobulin A (IgA). CS-DS nanoparticles were prepared using a complex coacervation (polyelectrolyte complexation) technique. CS-DS nanoparticle formulations with size and zeta potential in a range of 300-350 nm and +40-+55 mV, respectively, were obtained. An entrapment efficiency of more than 90% was obtained for pertussis toxin and IgA in CS-DS nanoparticles. All loaded nanoparticle formulations showed less than 20% of release within 24 h in in vitro release studies. The immunological evaluation of developed formulations in female Balb/c mice groups showed that the CS-DS nanoparticles formulations induced significantly higher serum IgG and IgG1 titers (p < 0.05) as compared with conventional alum-adjuvanted PTXd formulation administered by subcutaneous route. This study indicated the potential of CS-DS nanoparticles to be a simple and effective particulate delivery system with in-built immunological adjuvant property for acellular protein antigens. The study also revealed the potential important role of IgA-loaded CS-DS nanoparticles as a novel immunological adjuvant for vaccine delivery.
本研究的目的是评估壳聚糖-葡聚糖硫酸酯(CS-DS)纳米颗粒载体吸附百日咳毒素(PTXd)的免疫活性,及其与潜在免疫佐剂免疫球蛋白 A(IgA)联合的效果。采用复凝聚(聚电解质复合)技术制备 CS-DS 纳米颗粒。CS-DS 纳米颗粒制剂的粒径和 Zeta 电位分别在 300-350nm 和+40-+55mV 范围内。PTXd 和 IgA 在 CS-DS 纳米颗粒中的包封效率均超过 90%。在体外释放研究中,所有负载纳米颗粒制剂在 24 小时内的释放率均低于 20%。在雌性 Balb/c 小鼠组中对所开发制剂的免疫学评价表明,与皮下给予常规铝佐剂吸附 PTXd 制剂相比,CS-DS 纳米颗粒制剂诱导的血清 IgG 和 IgG1 滴度显著更高(p<0.05)。这项研究表明 CS-DS 纳米颗粒具有成为简单有效的蛋白抗原颗粒传递系统的潜力,同时具有内在的免疫佐剂特性。该研究还揭示了负载 IgA 的 CS-DS 纳米颗粒作为新型免疫佐剂在疫苗传递中的潜在重要作用。