School of Pharmacy, China Pharmaceutical University, No. 24 Tongjia Xiang, Nanjing 210009, PR China; School of Pharmacy, Nantong University, No.19 Qixiu Road, Nantong 226001, PR China.
School of Pharmacy, China Pharmaceutical University, No. 24 Tongjia Xiang, Nanjing 210009, PR China.
Int J Biol Macromol. 2018 Jul 1;113:534-542. doi: 10.1016/j.ijbiomac.2018.02.016. Epub 2018 Feb 3.
The aim of this study was to develop a novel biodegradable polymeric carrier for the delivery of protein vaccine orally in order to target the antigen presenting cells (APCs) in the region of Peyer's patches (PPs). Here, bovine serum albumin (BSA) was chosen as a model protein vaccine and was loaded into the mannosylated chitosan nanoparticles (MCS NPs) by ionic gelation method with tripolyphosphate (TPP), followed by coating MCS NPs with Eudragit® L100 (Eud) by electrostatic interaction. The spherical NPs were successfully prepared with appropriate particle size around 558.2±35.6nm, high entrapment efficiency about 90.38±9.12%, good stability and reasonable release behavior in the simulated gastrointestinal fluid, meanwhile high resistance of enzymatic and acid degradations were verified. The targeting ability of the NPs to PPs in rat was investigated by a closed ileal loop assay, where fluorescence visualization was performed. MCS NPs were accumulated more specifically into PPs after Eudragit® L100 dissolved in intestinal juices. Oral immunization using BSA-loaded Eudragit® L100-coated MCS NPs was found to elicit strong systemic IgG antibody and mucosal IgA responses. These results suggested that enteric-coated MCS NPs could serve as a promising carrier for oral protein vaccine delivery.
本研究旨在开发一种新型可生物降解聚合物载体，用于口服递送蛋白质疫苗，以靶向派伊尔氏结（PPs）中的抗原提呈细胞（APCs）。在这里，牛血清白蛋白（BSA）被选为模型蛋白质疫苗，并通过离子凝胶法与三聚磷酸（TPP）将其载入甘露糖化壳聚糖纳米颗粒（MCS NPs）中，随后通过静电相互作用用 Eudragit® L100（Eud）包被 MCS NPs。成功制备了具有适当粒径（约 558.2±35.6nm）、高包封效率（约 90.38±9.12%）、良好稳定性和合理释放行为的球形 NPs，同时验证了其对酶和酸降解的高抗性。通过封闭回肠袢试验研究了 NPs 对大鼠 PPs 的靶向能力，并进行了荧光可视化。当 Eudragit® L100 在肠液中溶解时，MCS NPs 更特异性地积聚到 PPs 中。使用负载 BSA 的 Eudragit® L100 包被的 MCS NPs 进行口服免疫接种，发现可引起强烈的全身 IgG 抗体和黏膜 IgA 反应。这些结果表明，肠溶性 MCS NPs 可以作为口服蛋白质疫苗递送的有前途的载体。
