壳聚糖
免疫系统
纳米载体
抗原
口服
化学
体内
微生物学
药理学
免疫学
药物输送
生物化学
生物
生物技术
有机化学
作者
Pei Cao,Felicity Y. Han,Lisbeth Grøndahl,Zhi Ping Xu,Li Li
出处
期刊:ACS omega
[American Chemical Society]
日期:2020-07-17
卷期号:5 (29): 18185-18197
被引量:35
标识
DOI:10.1021/acsomega.0c01792
摘要
Oral administration of vaccines has been limited due to low immune response compared to parenteral administration. Antigen degradation in the acidic gastrointestinal environment (GI), mucus barriers, and inefficient cellular uptake by immune cells are the major challenges for oral vaccine delivery. To solve these issues, the current study investigates calcium phosphate nanoparticles (CaP NPs) coated with polysaccharides as nanocarriers for oral protein antigen delivery. In this design, the CaP NP core had an optimized antigen encapsulation capacity of 90 mg (BSA-FITC)/g (CaP NPs). The polysaccharides chitosan and alginate were coated onto the CaP NPs to protect the antigens against acidic degradation in the GI environment and enhance the immune response in the small intestine. The antigen release profiles showed that alginate-chitosan-coated CaP NPs prevented antigen release in a simulated gastric fluid (pH 1.2), followed by sustained release in simulated intestinal (pH 6.8) and colonic (pH 7.4) fluids. Cellular uptake and macrophage stimulation data revealed that the chitosan coating enhanced antigen uptake by intestine epithelia cells (Caco-2) and macrophages and improved surface expression of costimulatory molecules on macrophages. In vivo test further demonstrated that oral administration of alginate-chitosan-coated CaP@OVA NPs significantly enhanced the mucosal IgA and serum IgG antibody responses as compared to naked OVA, indicating that the CaP-Chi-Alg nanoparticle can potentially be used as a promising oral vaccine delivery system.
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