US EPA

1104426 

Journal Article 

Interferon-gamma liposomes: Drug binding properties and antiviral in vitro activity 

Herrmann, J; Stricker, H 

1995 

1 

European Journal of Pharmaceutics and Biopharmaceutics
ISSN: 0939-6411
EISSN: 1873-3441 

41 

6 

English 

Recombinant human interferon-gamma (IFN-gamma), a promising protein drug with immunomodulating properties, was adsorbed to the surface of multilamellar liposomes by simple incubation (adsorption method) or encapsulated in liposomes (encapsulation method), in order to identify crucial parameters for the formulation of a potential liposomal IV-dosage form. By incorporating negatively charged phospholipids (e.g. dipalmitoylphosphatidylserine) into the liposomal membrane, the amount of liposome-bound interferon-gamma was multiplied compared with uncharged liposomes, due to electrostatic interactions between the cationic protein and the anionic liposomes. The specific antiviral activity of interferon-gamma- adsorbed to negatively charged liposomes increased with increasing drug loadin,g. The adsorption to liposomes prepared from negatively charged phospholipids caused a lower reduction in biological activity than the adsorption to neutral liposomes. The encapsulation method resulted in aroximately 50-180% higher binding rates than the absorption method. The stability profile of liposome-bound interferon-gamma, monitored in vitro as a decrease in antiviral activity, was comparable to that of aqueous drug solutions. Interferon-gamma solutions with a concentration < 25 mu g ml(-1) lost part of the dissolved protein by adsorption to the container walls, two other interferon fractions had a different storage stability profile. Desorption of interferon-gamma from the liposome surface at 37 degrees C was slow and the presence of human serum albumin did not lead to a significant displacement of liposome-bound interferon-gamma.