Surface-modified P(HEMA-co-MAA) nanogel carriers for oral vaccine delivery: design, characterization, and in vitro targeting evaluation.
Surface-modified P(HEMA-co-MAA) nanogel carriers for oral vaccine delivery: design, characterization, and in vitro targeting evaluation.
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DOI：
10.1021/bm500588x
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发表时间：
2014-07-14
影响因子：
6.2
通讯作者：
Peppas NA
中科院分区：
文献类型：
--
作者：
Durán-Lobato M;Carrillo-Conde B;Khairandish Y;Peppas NA
口服给药是疫苗给药的一种选择途径，因为它是非侵入性的，因此努力的重点是将疫苗抗原有效地输送到粘膜部位。一个有效的口服疫苗递送系统必须保护抗原在粘膜递送时不被降解，穿透粘膜屏障，并控制抗原以及共刺激和免疫调节剂向特定免疫细胞(即APC)的释放。本文合成了甘露聚糖改性的pH响应型P(HEMA-co-MAA)纳米凝胶，并对其作为口服疫苗载体进行了评价。纳米凝胶表现出对pH敏感的性质，在低pH值下对装载的货物进行包埋和保护，并在切换到肠道pH值后触发蛋白质释放。以甘露聚糖为碳水化合物的表面修饰可增强巨噬细胞的内化，并增加相关共刺激分子的表达。这些发现表明，甘露聚糖改性的P(HEMA-co-MAA)纳米凝胶是一种很有希望的更有效的口服疫苗接种方案。
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.