Citation: Luyu Zhang, Zirong Dong, Shuai Yu, Guangyue Li, Weiwen Kong, Wenjuan Liu, Haisheng He, Yi Lu, Wei Wu, Jianping Qi. Ionic liquid-based in situ dynamically self-assembled cationic lipid nanocomplexes (CLNs) for enhanced intranasal siRNA delivery[J]. Chinese Chemical Letters, ;2024, 35(7): 109101. doi: 10.1016/j.cclet.2023.109101 shu

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

Luyu Zhang ^a ,
Zirong Dong ^a ,
Shuai Yu ^b ,
Guangyue Li ^c ,
Weiwen Kong ^a ,
Wenjuan Liu ^a ,
Haisheng He ^a ,
Yi Lu ^a ,
Wei Wu ^a ,
Jianping Qi ^{a, *,}

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

qijianping@fudan.edu.cn

Received Date: 29 June 2023
Revised Date: 13 September 2023
Accepted Date: 14 September 2023
Available Online: 16 September 2023

Figures(4)

This research aims to develop a non-invasive strategy for small interfering RNA (siRNA) nasal delivery 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 simultaneously 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.
- Ionic liquids,
- Cationic lipids,
- Lipid nanoparticles,
- siRNA,
- Allergic rhinitis
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