Pharmacokinetic study of liposome-encapsulated human interferon-gamma after intravenous and intramuscular injection in mice.
We encapsulated human interferon-gamma (HuIFN-gamma) into liposomes and analyzed whether this preparation prevented the rapid decay of IFN-gamma in the serum of C57BL/6 mice after intravenous or intramuscular injection. Furthermore, we compared the serum decay curve of liposomal and free IFN-gamma. Whereas the intramuscular injection of IFN-gamma resulted in a serum curve with entrance compartment and subsequent biphasic elimination, intravenously injected IFN-gamma was distributed and eliminated in a biphasical manner from serum. Extremely prolonged serum titers are caused by IFN-gamma liposomes with a phospholipid composition of dimyristoylphosphatidylcholine/cholesterol/dicetylphosphate and an average particle size of 333 nm. Intramuscular injection of 2.5 mumoles liposome suspension with an antiviral activity of 4.3 x 10(3) IU/mouse resulted in longer-lasting serum titers than intravenously injected liposomes of a different charge with 2.5 mumoles and 1.2 x 10(5) IU/mouse. Liposomes after intravenous injection could be detected for up to 62 h at a titer of 20 IU/ml serum. Intramuscularly injected liposomes of the lower activity still had a titer of 30-80 IU/ml after 80 h p.i.
Rutenfranz
I
I
Institute of Immunology and Transfusion Medicine, University of Lübeck, FRG.
Bauer
A
A
Kirchner
H
H
D000818:Animals; D004337:Drug Carriers; D007273:Injections, Intramuscular; D007275:Injections, Intravenous; D007371:Interferon-gamma / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D008081:Liposomes; D051379:Mice; D008810:Mice, Inbred C57BL
D004337:Drug Carriers; D008081:Liposomes; D007371:Interferon-gamma