Original articles
Xiaotong Yang, Xianchun Chen, Ting Lei, Lin Qin, Yang Zhou, Chuan Hu, Qingfeng Liu, Huile Gao. The construction of in vitro nasal cavity-mimic M-cell model, design of M cell-targeting nanoparticles and evaluation of mucosal vaccination by nasal administration[J]. Acta Pharmaceutica Sinica B, 2020, 10(6): 1094-1105

The construction of in vitro nasal cavity-mimic M-cell model, design of M cell-targeting nanoparticles and evaluation of mucosal vaccination by nasal administration
Xiaotong Yanga, Xianchun Chenb, Ting Leia, Lin Qina, Yang Zhoua, Chuan Hua, Qingfeng Liuc, Huile Gaoa
a Key Laboratory of Drug Targeting and Drug Delivery System of the Education Ministry, Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy Sichuan University, Chengdu 610041, China;
b College of Materials Science and Engineering, Sichuan University, Chengdu 610064, China;
c Shanghai University of Medicine & Health Sciences Affiliated Sixth People's Hospital South Campus, Shanghai 201499, China
Abstract:
In order to better evaluate the transport effect of nanoparticles through the nasal mucosa, an in vitro nasal cavity-mimic model was designed based on M cells. The differentiation of M cells was induced by co-culture of Calu-3 and Raji cells in invert model. The ZO-1 protein staining and the transport of fluorescein sodium and dexamethasone showed that the inverted co-culture model formed a dense monolayer and possessed the transport ability. The differentiation of M cells was observed by upregulated expression of Sialyl Lewis A antigen (SLAA) and integrin β1, and down-regulated activity of alkaline phosphatase. After targeting M cells with iRGD peptide (cRGDKGPDC), the transport of nanoparticles increased. In vivo, the co-administration of iRGD could result in the increase of nanoparticles transported to the brain through the nasal cavity after intranasal administration. In the evaluation of immune effect in vivo, the nasal administration of OVA-PLGA/iRGD led to more release of IgG, IFN-γ, IL-2 and secretory IgA (sIgA) compared with OVA@PLGA group. Collectively, the study constructed in vitro M cell model, and proved the enhanced effect of targeting towards M cell with iRGD on improving nasal immunity.
Key words:   
Received: 2020-01-07     Revised: 2020-02-13
DOI: 10.1016/j.apsb.2020.02.011
Funds: The work was supported by National Natural Science Foundation of China (81603057), Research Funds of Sichuan Science and Technology Department (2019YJ0048 and 19YYJC2250, China), the Fundamental Research Funds for the Central Universities (China), and 111 Project (B18035, China).
Corresponding author: Qingfeng Liu, Huile Gao     Email:155135562@qq.com;gaohuile@scu.edu.cn
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Xiaotong Yang
Xianchun Chen
Ting Lei
Lin Qin
Yang Zhou
Chuan Hu
Qingfeng Liu
Huile Gao

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