Ionic liquid-based in situ dynamically self-assembled cationic lipid nanocomplexes(CLNs)for enhanced intranasal siRNA delivery

Luyu Zhang ¹Zirong Dong ¹Shuai Yu ²Guangyue Li ³Weiwen Kong ¹Wenjuan Liu ¹Haisheng He ¹Yi Lu ¹Wei Wu ¹Jianping Qi¹

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作者信息

1. Key Laboratory of Smart Drug Delivery of MOE,School of Pharmacy,Fudan University,Shanghai 201203,China
2. School of Pharmacy,Shandong Academy of Sciences,Qilu University of Technology,Ji'nan 250353,China
3. College of Chemical Engineering,North China University of Science and Technology,Tangshan 063210,China
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Abstract

This research aims to develop a non-invasive strategy for small interfering RNA(siRNA)nasal deliv-ery based on ionic liquids(ILs)and cationic lipid(2,3-dioleoyloxy-propyl)-trimethylammonium-chloride(DOTAP).Other than the classical role of penetration enhancer,ILs also acted as superior solvents to si-multaneously load siRNA and DOTAP,forming siRNA-DOTAP-ILs(siRNA-DILs)formulations.During nasal mucosa penetration,DOTAP and ILs components self-assembled into cationic lipid nanocomplexes to load siRNA for enhanced in situ transfection.The siRNA-DILs demonstrated resistance against RNase,significant mucosa penetration,prolonged nasal retention,and satisfying gene-silencing efficacy at lower dosage.Meanwhile,DILs were also able to deliver KCa3.1-targeted siRNA effectively for the treatment of allergic rhinitis in rat model by nasal route.Thus,DILs have great potentials to deliver biological macromolecules across nasal mucosa by in situ dynamic self-assembly.

Key words

Ionic liquids/Cationic lipids/Lipid nanoparticles/siRNA/Allergic rhinitis

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基金项目

National Natural Science Foundation of China(82073801)

出版年

2024

中国化学快报(英文版)

中国化学会

中国化学快报(英文版)

CSTPCDCSCD

影响因子：0.771

ISSN：1001-8417

参考文献量25

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