Pharmacokinetic Study of Liposome-Encapsulated Human Interferon-γ after Intravenous and Intramuscular Injection in Mice

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Abstract
We encapsulated human interferon-γ (HuIFN-γ) into liposomes and analyzed whether this preparation prevented the rapid decay of IFN-γ in the serum of C57BL/6 mice after intravenous or intramuscular injection. Furthermore, we compared the serum decay curve of liposomal and free IFN-γ. Whereas the intramuscular injection of IFN-γ resulted in a serum curve with entrance compartment and subsequent biphasic elimination, intravenously injected IFN-γ was distributed and eliminated in a biphasical manner from serum. Extremely prolonged serum titers are caused by IFN-γ liposomes with a phospholipid composition of dimyristoylphosphatidylcholine/cholesterol/dicetylphosphate and an average particle size of 333 nm. Intramuscular injection of 2.5 μmoles liposome suspension with an antiviral activity of 4.3 × 103 IU/mouse resulted in longer-lasting serum titers than intravenously injected liposomes of a different charge with 2.5 μmoles and 1.2 × 105 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.