Effect of absorption enhancers on nasal delivery of basic fibroblast growth factor

Abstract

The present study was to screen an optimal absorption enhancer for enhancing the nasal absorption of basic 
fibroblast growth factor (bFGF), a promising therapeutic agent to neurodegenerative diseases. In this study, four 
absorption enhancers including chitosan, sodium caprate, poly-L-arginine (poly-L-Arg, 92.0 kDa) and dimethyl- 
cyclodextrin were chosen to evaluate their toxicity using in situ toad palate model and in vitro Calu -3 cell model. 
Transport study of bFGF across Calu-3 cell monolayers in the absence or presence of chitosan was performed to 
determine the optimal concentration of chitosan. Pharmacokinetics study was conducted to monitor changes in the 
blood concentration of bFGF following nasal administration of bFGF solution with or without 0.5% (w/v) chitoson, in 
comparison with intravenous administration of bFGF alone. Of the absorption enhancers tested, chitosan at the 
concentration of 0.25 and 0.5% showed little toxicity to nasal cilia and Calu-3 cells, and exerted reversible effect on 
the reduction of transepithelial electrical resistance. Transport study showed that the apparent permeability 
coefficient (Papp) value was increased by about 16- and 2-fold, respectively with addition of 0.5 and 0.25% chitosan, 
compared with bFGF solution alone. Following nasal administration to rats, the formulation containing 0.5% chitosan 
significantly enhanced the absorption of bFGF with an area under curve (AUC0-120min) nearly 1.4-fold that of bFGF 
solution (p<0.05). The absolute bioavailability of bFGF after intranasal administration was 5.35 and 7.53% for bFGF 
alone and 0.5% chitosan group, respectively. These results indicated that 0.5% chitosan is a safe and effective 
absorption enhancer for intranasal delivery of bFGF.