Effect of poly- l-arginine on the nasal absorption of FITC-dextran of different molecular weights and recombinant human granulocyte colony-stimulating factor (rhG-CSF) in rats

Abstract

The effect of poly- l-arginine (poly- l-Arg) on the in vivo nasal absorption of FITC-dextrans with a mean molecular weight ranging from 4.3 to 167 kDa and recombinant human granulocyte colony-stimulating factor (rhG-CSF) in rats were studied. When FITC-dextrans were co-administered intranasally with 1.0 w/v% poly- l-Args of different molecular weight (MW, ca. 45.5 and 92 kDa, poly- l-Arg (50) and poly- l-Arg (100)), the bioavailability ( F ∞) increased markedly compared with that after administration of FITC-dextran alone. However, the F ∞ decreased exponentially with the increasing molecular weight of FITC-dextrans. There was no significant difference between the enhanced nasal absorption of FITC-dextrans achieved by the co-administration of poly- l-Arg (50) and poly- l-Arg (100). Moreover, the relationship between the F ∞ and the molecular weight of FITC-dextrans indicated that the molecular weight of protein drugs, which exhibited efficient absorption with poly- l-Arg, was about 20 kDa, when the lower limit of bioavailability for developing a potent transnasal delivery system was assumed to be about 10%. Indeed, the nasal absorption of rhG-CSF, which has a molecular weight of 18.8 kDa, was also increased after co-administration of 1.0 w/v% poly- l-Arg (50) and the F ∞ was about 11%. It seems likely that poly- l-Arg can be used to provide adequate nasal absorption of various protein drugs which have a molecular weight of about 20 kDa, thereby allowing the successful development of a variety of transnasal drug delivery systems.