Intranasal absorption of granulocyte-colony stimulating factor (G-CSF) from powder formulations, in sheep.
Granulocyte-colony stimulating factor (G-CSF) was administered to sheep in three different nasal formulations and as a subcutaneous injection. The nasal formulations were: a solution containing L-alpha-lysophosphatidylglycerol (LPG), a powder formulation comprising small starch microspheres (SSMS) and a powder formulation comprising SSMS and LPG. Absorption 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-CSF powder formulation containing SSMS and LPG the absorption of G-CSF was significantly higher (P<0.01) than that from the simple nasal solution or the powder without the enhancer, but the resulting pharmacological 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 the respective G-CSF doses investigated, the pharmacodynamic response of this nasal formulation, was similar to that obtained after the subcutaneous administration. The study indicates that the powder formulation containing enhancers could offer an alternative delivery route for G-CSF in the form of intranasal administration.
Gill
I J
IJ
Danbiosyst UK Ltd, Albert Einstein Centre, Highfields Science Park, Nottingham, NG7 2TN, UK.
Fisher
A N
AN
Farraj
N
N
Pitt
C G
CG
Davis
S S
SS
Illum
L
L
D000281:Administration, Intranasal; D000818:Animals; D001682:Biological Availability; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D006801:Humans; D007279:Injections, Subcutaneous; D008246:Lysophospholipids / Q000737:chemistry; D011208:Powders / Q000737:chemistry*; D012756:Sheep; D012996:Solutions / Q000737:chemistry; D013213:Starch / Q000737:chemistry
D008246:Lysophospholipids; D011208:Powders; D012996:Solutions; C083286:degradable starch microspheres; C026223:lysophosphatidylglycerol; D016179:Granulocyte Colony-Stimulating Factor; D013213:Starch