Abstract：
Oral delivery of cells, such as probiotics and vaccines, has proved to be inefficient since cells are generally damaged in an acidic stomach prior to arrival at the intestine to exert their health benefits. In addition, short retention in the intestine is another obstacle which affects inefficiency. To overcome these obstacles, a cell-in-shell structure was designed with pH-responsive and mucoadhesive properties. The pH-responsive shell consisting of three cationic layers of chitosan and three anionic layers of trans-cinnamic acid (t-CA) was made via layer-by-layer (LbL) assembly. t-CA layers are hydrophobic and impermeable to protons in acid, thus enhancing cell gastric resistance in the stomach, while chitosan layers endow strong interaction between the cell surface and the mucosal wall which facilitates cell mucoadhesion in the intestine. Two model cells, probiotic L. rhamnosus GG and dead Streptococcus iniae, which serve as inactivated whole-cell vaccine were chosen to test the design. Increased survival and retention during oral administration were observed for coated cells as compared with naked cells. Partial removal of the coating (20-60% removal) after acid treatment indicates that the coated vaccine can expose its surface immunogenic protein after passage through the stomach, thus facilitating vaccine immune stimulation in the intestine. As a smart oral delivery platform, this design can be extended to various macromolecules, thus providing a promising strategy to formulate oral macromolecules in the prevention and treatment of diseases at a cellular level.
摘要：
口服细胞，比如益生菌和疫苗，已被证明是无效的，因为细胞通常在到达肠道之前在酸性胃中受损以发挥其健康益处。此外,在肠道中的短暂滞留是影响低效率的另一个障碍。为了克服这些障碍,设计了具有pH响应性和粘膜粘附特性的壳细胞结构。通过逐层（LbL）组装制备了由三个壳聚糖阳离子层和三个反式肉桂酸（t-CA）阴离子层组成的pH响应壳。t-CA层是疏水性的，对酸性中的质子是不可渗透的，从而增强胃中细胞胃的抵抗力，而壳聚糖层赋予细胞表面和粘膜壁之间的强相互作用，促进细胞在肠道中的粘膜粘附。两个模型细胞，益生菌鼠李糖乳杆菌GG和死亡链球菌，选择作为灭活的全细胞疫苗来测试设计。与裸细胞相比,观察到包被细胞在口服施用期间的存活和保留增加。酸处理后涂层的部分去除（20-60％去除）表明涂层的疫苗在通过胃后可以暴露其表面免疫原性蛋白，从而促进疫苗在肠道中的免疫刺激。作为智能口腔分娩平台，这种设计可以扩展到各种大分子，因此提供了在细胞水平上预防和治疗疾病中配制口服大分子的有前途的策略。
