INTRANASAL ABSORPTION OF GRANULOCYTE-COLONY-STIMULATING FACTOR (G-CSF) FROM POWDER FORMULATIONS, IN SHEEP

Granulocyte-colony stimulating factor (G-CSF) was administered to shee p in three different nasal formulations and as a subcutaneous injectio n. The nasal formulations were: a solution containing L-alpha-lysophos phatidylglycerol (LPG), a powder formulation comprising small starch m icrospheres (SSMS) and a powder formulation comprising SSMS and LPG. A bsorption of G-CSF was assessed directly by quantitation in plasma and indirectly by measurement of the pharmacodynamic response in terms of leucocyte and neutrophil counts. After the nasal delivery of the G-CS F powder formulation containing SSMS and LPG the absorption of G-CSF w as significantly higher (P < 0.01) than that from the simple nasal sol ution or the powder without the enhancer, but the resulting pharmacolo gical response was not significantly different. The bioavailability of G-CSF from the powder formulation containing SSMS and LPG relative to the subcutaneous injection was 8.4% (+/-3.4). We also found that at t he respective G-CSF doses investigated, the pharmacodynamic response o f this nasal formulation, was similar to that obtained after the subcu taneous administration. The study indicates that the powder formulatio n containing enhancers could offer an alternative delivery route for G -CSF in the form of intranasal administration. (C) 1998 Elsevier Scien ce B.V.