Abstract
The effects of various surfactants and protease inhibitors on the nasal absorption of recombinant human granulocyte colony-stimulating factor (rhG-CSF) were examined in rats. No effects of bile salts and acids such as sodium glycocholate or taurocholic acid, amphoteric surfactants such as lauryldimethyl betaine, or anionic surfactants such as sodium lauryl sulfate on the absorption were found at a concentration of 1%. But non-ionic surfactants with hydrophile/lipophile balance (HLB) of 13 to 18 increased the total leukocyte numbers maximally by about 250% as a relative increase ratio to the control without surfactants. The increase in the plasma rhG-CSF concentration was obviously observed only in the presence of non-ionic surfactants, and in particular, the effects of Laureth-9 on the increase in total leukocyte numbers and plasma rhG-CSF concentration were maximal. In the presence of various kinds of protease inhibitors, the increasing effect of rhG-CSF on the total leukocyte numbers was not changed. Consequently, it is considered that the permeation of rhG-CSF through the nasal epithelium can be improved by non-ionic surfactants, but the effect of a protease inhibitor is smaller than that of the surfactant.
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