Lipoplex-mediated gene delivery to the lung occurs within 60 minutes of intravenous administration.
We have defined the critical time period for gene delivery in the lung after intravenous administration of cationic lipoplex. We accomplished this through the displacement of intravenously injected cationic lipoplexes from the lungs by the subsequent administration of anionic liposomes. When reporter gene-bearing lipoplexes were injected intravenously and followed by anionic liposomes 5 min later, reporter gene expression was reduced up to 400-fold compared with animals into which lipoplex alone was administered. Administration of anionic liposomes 60-90 min after lipoplex injection yielded no significant reduction in lung transfection. When lipoplexes were disrupted 5 min after administration, the pulmonary distribution of the cationic lipid and DNA components was reduced by 80%. Lipids subsequently accumulated primarily in the liver, while the plasmid DNA constituent distributed into the blood and liver. As the interval between lipoplex and anionic liposome injection increased, the degree of lipoplex displacement from the lung decreased to such a point that, 60 min after lipoplex injection, the anionic liposome injection did not displace significant quantities of the lipoplex. We conclude that cationic lipid-DNA complexes can be disrupted in vivo via the administration of anionic liposomes; moreover, we have employed this phenomenon to demonstrate that transfectionally active DNA is taken up within 60 min of systemic lipoplex administration.
Barron
L G
LG
Department of Biopharmaceutical Sciences, School of Pharmacy, University of California, San Francisco, 94143-0446, USA.
Gagné
L
L
Szoka
F C
FC
D000818:Animals; D000838:Anions; D002412:Cations; D004337:Drug Carriers; D005260:Female; D018014:Gene Transfer Techniques; D007275:Injections, Intravenous; D008055:Lipids; D008081:Liposomes; D008156:Luciferases / Q000235:genetics; D008168:Lung; D051379:Mice; D010957:Plasmids; D013997:Time Factors
D000838:Anions; D002412:Cations; D004337:Drug Carriers; D008055:Lipids; D008081:Liposomes; D008156:Luciferases