Immersion delivery of plasmid DNA. I. A study of the potentials of a liposomal delivery system in rainbow trout (Oncorhynchus mykiss) fry.
A successful regime for intramuscular injection of naked DNA is developed in fish, but the exploration of other ways of administration has not yet been studied in any detail. Immersion is a delivery route offering many advantages compared to conventional ways of administration. Applying cationic liposomes as a delivery system for DNA by this route, however, is met with severe toxicity problems. In this report, the underlying mechanisms of the acute toxicity were investigated in vivo and in vitro. The most critical factor was found to be the charge of the liposomes. Cationic liposomes above a certain threshold concentration had a lethal effect in rainbow trout fry. In contrast, similar concentrations of neutral or anionic liposomes were not toxic. Furthermore, large liposome-mucin complexes were formed upon addition of mucin to cationic liposomes. This was not observed with neutral or anionic liposomes. Lipoplexes were less toxic and interacted less with mucin compared to cationic liposomes. Hence, the mechanism of the acute toxicity in rainbow trout fry is suggested to be an interaction between the cationic liposomes and anionic components of gill mucin. The consequence is hypoxia and this is most likely the cause of acute toxicity observed in rainbow trout fry.
Romøren
Kristine
K
Department of Pharmaceutics, School of Pharmacy, University of Oslo, PO Box 1068, Blindern, N-0316, Oslo, Norway. kristine.romoren@farmasi.uio.no
Thu
Beate J
BJ
Smistad
Gro
G
Evensen
Øystein
Ø
D000818:Animals; D016503:Drug Delivery Systems / Q000379:methods*; D049454:Firefly Luciferin / Q000032:analysis; D007101:Immersion; D008081:Liposomes / Q000032:analysis / Q000633:toxicity*; D017686:Oncorhynchus mykiss / Q000378:metabolism*; D010957:Plasmids / Q000008:administration & dosage* / Q000032:analysis; D015996:Survival Rate
D008081:Liposomes; D049454:Firefly Luciferin