School of Pharmacy, University of Lincoln, Joseph Banks Laboratories, Green Lane, Lincoln, LN6 7DL, United Kingdom.
Bacteriology Division, The National Institute for Biological Standards and Control (NIBSC), Blanche Lane, South Mimms, Potters Bar, EN6 3QG, United Kingdom.
Carbohydr Polym. 2018 Jun 15;190:248-254. doi: 10.1016/j.carbpol.2018.02.084. Epub 2018 Feb 27.
This study compared in vitro and in vivo antigen delivery effects of ultrapure chitosan (CS) chloride. CS nanoparticles were formulated to incorporate ovalbumin (OVA) as a model antigen and characterised for size, charge, OVA complexation and release. The effect of CS:OVA nanoparticles on cell viability, epithelial tight junctions and transepithelial permeation of OVA was tested on Caco-2 monolayer in vitro intestinal model. The system's ability to elicit immune responses was subsequently tested in vivo. The work confirmed that CS complexes with OVA into nano-size entities. Nanocomplexes displayed favourable delivery properties, namely OVA release and no notable cytotoxicity. CS:OVA markedly enhanced antigen delivery across Caco-2 monolayers. However, the system did not elicit notable in vivo immune responses (some mucosal response was apparent) following oral delivery. The study highlights that a clear effect on antigen permeability across epithelial monolayers in vitro may predict the in vivo mucosal but not systemic immune response following oral delivery.
本研究比较了超纯几丁聚糖（CS）氯化物的体外和体内抗原递呈效果。将 CS 纳米颗粒制成含有卵清蛋白（OVA）的模型抗原，并对其大小、电荷、OVA 复合和释放进行了表征。在体外肠道模型 Caco-2 单层上，测试了 CS:OVA 纳米颗粒对细胞活力、上皮紧密连接和 OVA 经上皮渗透的影响。随后在体内测试了该系统引发免疫反应的能力。这项工作证实 CS 可将 OVA 复合成纳米大小的实体。纳米复合物表现出良好的递药特性，即 OVA 释放和无明显细胞毒性。CS:OVA 显著增强了 OVA 在 Caco-2 单层中的传递。然而，该系统在口服给药后并未引起明显的体内免疫反应（出现了一些黏膜反应）。该研究表明，体外上皮单层中抗原通透性的明显影响可能预测口服给药后黏膜但不是系统免疫反应。
