Enhanced intranasal delivery of mRNA vaccine by overcoming the nasal epithelial barrier via intra- and paracellular pathways

被引：158

作者：

Li, Man ^{[1
]}

Zhao, Mengnan ^{[1
]}

Fu, Yao ^{[1
]}

Li, You ^{[1
]}

Gong, Tao ^{[1
]}

Zhang, Zhirong ^{[1
]}

Sun, Xun ^{[1
]}

机构：

[1] Sichuan Univ, West China Sch Pharm, Minist Educ, Key Lab Drug Targeting, Chengdu 610041, Peoples R China

来源：

JOURNAL OF CONTROLLED RELEASE | 2016年 / 228卷

基金：

中国国家自然科学基金;

关键词：

mRNA vaccination; CD-PEI; Nasal epithelial barrier; Intracellular delivery; Paracellular delivery; IN-VITRO; IMMUNE-RESPONSES; DRUG-DELIVERY; DENDRITIC CELLS; LYMPHOID-TISSUE; GENE DELIVERY; HIV-1; CHITOSAN; CANCER; NANOPARTICLES;

D O I：

10.1016/j.jconrel.2016.02.043

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

Facing the threat of highly variable virus infection, versatile vaccination systems are urgently needed. Intranasal mRNA vaccination provides a flexible and convenient approach. However, the nasal epithelium remains a major biological barrier to deliver antigens to nasal associated lymphoid tissue (NALT). To address this issue, a potent polymer-based intranasal mRNA vaccination system for HIV-1 treatment was synthesized using cationic cyclodextrin-polyethylenimine 2k conjugate (CP 2k) complexed with anionic mRNA encoding HIV gp120. The delivery vehicle containing CP 2k and mRNA overcame the epithelial barrier by reversibly opening the tight junctions, enhanced the paracellular delivery of mRNA and consequently minimized absorption of toxins in the nasal cavity. Together with the excellent intracellular delivery and prolonged nasal residence time, strong system and mucosal anti-HIV immune responses as well as cytokine productions were achieved with a balanced Th1/Th2/Th17 type. Our study provided the first proof of evidence that cationic polymers can be used as safe and potent intranasal mRNA vaccine carriers to overcome the nasal epithelial barrier. The safe and versatile polymeric delivery system represents a promising vaccination platform for infectious diseases. (C) 2016 Elsevier B.V. All rights reserved.

引用

页码：9 / 19

页数：11

共 51 条

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