Center for Neuroscience and Cell Biology, University of Coimbra, Coimbra, 3004-517, Portugal; Faculty of Pharmacy, University of Coimbra, Pólo das Ciências da Saúde Azinhaga de Santa Comba Coimbra, 3000-548, Portugal.
Center for Neuroscience and Cell Biology, University of Coimbra, Coimbra, 3004-517, Portugal; Faculty of Pharmacy, University of Coimbra, Pólo das Ciências da Saúde Azinhaga de Santa Comba Coimbra, 3000-548, Portugal.
Int J Pharm. 2018 Jan 15;535(1-2):261-271. doi: 10.1016/j.ijpharm.2017.11.009. Epub 2017 Nov 11.
The World Health Organization encourages "the development of oral formulations to simplify their transport, storage and administration in poor countries", and to "facilitate an effective immunization program to prevent sexually transmitted hepatitis B". Thus, two distinct and promising delivery systems were developed: recombinant hepatitis B surface antigen (HBsAg) encapsulated into alginate-coated chitosan particles (AlgChiPs) and into glucan particles (GPs) mainly composed of β-1,3-d-glucan. In vitro preliminary studies showed that both could be internalized by peripheral blood mononuclear cells and murine Peyer's patches, an imperative aspect regarding oral immunization. Chitosan particles (ChiPs) have shown interesting immunostimulating properties as mast cells activators. Vaccination studies reveal that three oral immunizations induced serum anti-HBsAg Immunoglobulin G (IgG) in 60 % of the animals and anti-HBsAg secretory IgA in faeces for both formulations. When subcutaneous (SC) priming was done, followed by two oral boosts, all mice were responder and much higher serum anti-HBsAg IgG titers were observed, besides mucosal protective immunity.
世界卫生组织鼓励“开发口服制剂，以简化在贫穷国家的运输、储存和管理”，并“促进有效的免疫规划，以预防性传播乙型肝炎”。因此，开发了两种截然不同且有前途的递药系统：将重组乙型肝炎表面抗原（HBsAg）包封入藻酸盐包被的壳聚糖颗粒（AlgChiPs）和主要由β-1,3-d-葡聚糖组成的葡聚糖颗粒（GPs）。体外初步研究表明，这两种颗粒都可以被外周血单核细胞和小鼠派尔氏斑内吞，这是口服免疫的一个重要方面。壳聚糖颗粒（ChiPs）已显示出作为肥大细胞激活剂的有趣的免疫刺激特性。疫苗接种研究表明，两种制剂的 3 次口服免疫均可使 60%的动物血清抗-HBsAg 免疫球蛋白 G（IgG）和粪便中抗-HBsAg 分泌型 IgA 产生应答。当进行皮下（SC）初免，然后进行两次口服加强时，所有小鼠均有应答，并且观察到更高的血清抗-HBsAg IgG 滴度，以及黏膜保护性免疫。
