Effects of a Dosing Solution of the Nasal Absorption of Non-glycosylated Recombinant Human Graunlocyte Colony-Stimulating Factor in Rats

Abstract

The nasal absorption of non-glycosylated recombinant human granulocyte colony-stimulating factor produced by Esherichia coli (E. coli-rhG-CSF) was studied in rats. We investigated the effects of the basic conditions of the soding solution and the enhancing effects of various substances to find means to improve the nasal absorption of E. coli-rhG-CSF. Relative bioavaliability following the nasal administration of E. coli-rhG-CSF solution of subcutaneous administration was 3.6%. Osmotic pressure of the dosing solution had virtually no effect of the nasal absorption of E. coli-rhG-CSF. Absorption was enhanced by a decrease in pH, an increase in buffer concentration at pH 2 and an increase in drug concentration. Sodium cholate, ascorbic acid, tartaric acid, β-cyclodextrin and dimethyl-β-cyclodextrin remarkably increased the nasal absorption of E. coli-rhG-CSF. Condition adjustments to the dosing solution and the use of several enhancers were significantly concluded to increase the intranasal absorption of E. coli-rhG-CSF.