Stabilization of aerosolized IFN-gamma by liposomes.
Aerosolized IFN-gamma is very unstable. We have improved the stability of IFN-gamma in the jet nebulizer by adding small liposomes. Aerosolized IFN-gamma was recovered in PBS solution by bubbling and its concentration was determined. After nebulization for 30 min, aerosolized IFN-gamma was detected only 0.4+/-0.2% of the initial amount in the PBS solution and 3.1+/-0.7% in the reservoir. On the other hand, the addition of small liposomes (HSPC/DSPG=10/1 (molar ratio), 45+/-24 nm) in the nebulizer increased the stability of IFN-gamma, 27.2+/-4.7% of the initial amount in the PBS solution and 25.7+/-12.6% in the reservoir. The present study also examined the effects of composition and concentration of liposomes on the stabilization of aerosolized IFN-gamma. Liposome prepared from distearoyl phosphatidylcholine (DSPC) or hydrogenated soy phosphatidylcholine (HSPC) was very effective for stabilization of aerosolized IFN-gamma (DSPC/DPPG=10/1, HSPC/DSPG=10/1). HSPC/DSPG liposome was efficient at the concentration higher than 12.5 micromols/ml for the stabilization of 5x10(5) JRU/ml of IFN-gamma. In considering the mechanism of this stabilization, the results of gel filtration chromatography suggest that IFN-gamma is inactivated by polymerization or aggregation in nebulization, while the inactivation is suppressed by liposomes due to their adsorption to IFN-gamma.
Kanaoka
E
E
Formulation Research & Development Laboratories, Shionogi & Co., Ltd. 12-4, Sagisu 5, Fukushima-ku, Osaka, Japan.
Nagata
S
S
Hirano
K
K
D000336:Aerosols / Q000737:chemistry; D002626:Chemistry, Pharmaceutical; D004305:Dose-Response Relationship, Drug; D004339:Drug Compounding / Q000379:methods; D004355:Drug Stability; D007371:Interferon-gamma / Q000737:chemistry* / Q000187:drug effects; D008081:Liposomes / Q000737:chemistry* / Q000494:pharmacology; D009330:Nebulizers and Vaporizers
D000336:Aerosols; D008081:Liposomes; D007371:Interferon-gamma