Durán-Lobato Matilde, Carrillo-Conde Brenda, Khairandish Yasmine, Peppas Nicholas A
Department of Biomedical Engineering, §Department of Chemical Engineering, and ∥Division of Pharmaceutics, University of Texas at Austin , 1 University Station, C0800, Austin, Texas 78712-0238, United States.
Biomacromolecules. 2014 Jul 14;15(7):2725-34. doi: 10.1021/bm500588x. Epub 2014 Jul 2.
Oral drug delivery is a route of choice for vaccine administration because of its noninvasive nature and thus efforts have focused on efficient delivery of vaccine antigens to mucosal sites. An effective oral vaccine delivery system must protect the antigen from degradation upon mucosal delivery, penetrate mucosal barriers, and control the release of the antigen and costimulatory and immunomodulatory agents to specific immune cells (i.e., APCs). In this paper, mannan-modified pH-responsive P(HEMA-co-MAA) nanogels were synthesized and assessed as carriers for oral vaccination. The nanogels showed pH-sensitive properties, entrapping and protecting the loaded cargo at low pH values, and triggered protein release after switching to intestinal pH values. Surface decoration with mannan as carbohydrate moieties resulted in enhanced internalization by macrophages as well as increasing the expression of relevant costimulatory molecules. These findings indicate that mannan-modified P(HEMA-co-MAA) nanogels are a promising approach to a more efficacious oral vaccination regimen.
口服给药是疫苗接种的首选途径，因为其具有非侵入性，因此研究重点一直是将疫苗抗原有效递送至粘膜部位。有效的口服疫苗递送系统必须在粘膜递送时保护抗原不被降解，穿透粘膜屏障，并控制抗原以及共刺激和免疫调节因子向特定免疫细胞（即抗原呈递细胞）的释放。本文合成了甘露聚糖修饰的pH响应性聚（甲基丙烯酸羟乙酯-共-甲基丙烯酸）纳米凝胶，并评估其作为口服疫苗载体的性能。纳米凝胶表现出pH敏感特性，在低pH值下包裹并保护负载的物质，并在转变为肠道pH值后触发蛋白质释放。用甘露聚糖作为碳水化合物部分进行表面修饰导致巨噬细胞的内化增强，以及相关共刺激分子的表达增加。这些发现表明，甘露聚糖修饰的聚（甲基丙烯酸羟乙酯-共-甲基丙烯酸）纳米凝胶是实现更有效口服疫苗接种方案的一种有前景的方法。
