Three cationic lipids with lysylated（1）, histidylated（2）, and arginylated（3） headgroups and cholesterol hydrophobic moiety were synthesized. The average sizes of liposomes and lipoplexes were around 100 and 160 ...Three cationic lipids with lysylated（1）, histidylated（2）, and arginylated（3） headgroups and cholesterol hydrophobic moiety were synthesized. The average sizes of liposomes and lipoplexes were around 100 and 160 nm, respectively. The gene transfection efficiency of the three lipoplexes loaded with pGL3 or pORF-LacZ was compared on 293T cells in the presence or the absence of serum. The transfection efficiency of the three lipoplexes in a serum-free medium was 2 to 3-fold higher than that of dioleoyl-trimethylammonium propane（DOTAP）. In the presence of serum, however, most of the lipoplexes showed lower transfection activities; only lipoplex 3 retained its high transfection efficiency.展开更多
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 t...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.展开更多
Nucleic acid-based bioactive substances have recently emerged as a new class of nextgeneration therapeutics, but their development has been limited by their relatively weakdelivery into target cells. Cationic liposome...Nucleic acid-based bioactive substances have recently emerged as a new class of nextgeneration therapeutics, but their development has been limited by their relatively weakdelivery into target cells. Cationic liposomes have been studied as a means to enhance thestability of nucleic acid therapeutics in the bloodstream and improve their cellular delivery.As nucleic acid therapeutics, siRNA and plasmid DNA have been extensively tested fordelivery using cationic liposomes. This review discusses recent progress in the applicationof cationic liposomes for the delivery of nucleic acid therapeutics.展开更多
基金Supported by the National Basic Research Program of China(No.2005CB623903).
文摘Three cationic lipids with lysylated（1）, histidylated（2）, and arginylated（3） headgroups and cholesterol hydrophobic moiety were synthesized. The average sizes of liposomes and lipoplexes were around 100 and 160 nm, respectively. The gene transfection efficiency of the three lipoplexes loaded with pGL3 or pORF-LacZ was compared on 293T cells in the presence or the absence of serum. The transfection efficiency of the three lipoplexes in a serum-free medium was 2 to 3-fold higher than that of dioleoyl-trimethylammonium propane（DOTAP）. In the presence of serum, however, most of the lipoplexes showed lower transfection activities; only lipoplex 3 retained its high transfection efficiency.
基金supported by National Natural Science Foundation of China(No.82073801)。
文摘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.
基金This work was supported by Research Settlement Fund for the new faculty of Seoul National University,and grants from Ministry of Science,ICT and Future Planning(No.2013035166)from Business for Cooperative R&D between Industry,Academy,and Research Institute funded Korea Small and Medium Business Administration in 2012(No.C0010962).
文摘Nucleic acid-based bioactive substances have recently emerged as a new class of nextgeneration therapeutics, but their development has been limited by their relatively weakdelivery into target cells. Cationic liposomes have been studied as a means to enhance thestability of nucleic acid therapeutics in the bloodstream and improve their cellular delivery.As nucleic acid therapeutics, siRNA and plasmid DNA have been extensively tested fordelivery using cationic liposomes. This review discusses recent progress in the applicationof cationic liposomes for the delivery of nucleic acid therapeutics.
