Transdermal delivery of bFGF with sonophoresis facilitated by chitosan nanocarriers

The basic fibroblast growth factor (bFGF) is a potent angiogenic growth factor. Supplemental bFGF is essential for healing damaged skin, but its therapeutic use has been limited owing to its inherent instability. In this study, we propose a transdermal delivery system using sonophoresis along with the use of carboxymethyl chitosan nanocarriers which enables the administration of bFGF over a wide area of skin. The transdermal effect of the low-frequency ultrasound-enhanced delivery system was demonstrated in ex vivo experiments using hairless mouse skin. The subcutaneous administration of chitosan nanoparticles was evaluated by using fluorescence-labeled chitosan. To stably load bFGF into chitosan nanoparticles, a carrier with carboxymethyl chitosan was synthesized under a pH of around 7. Based on the results, we evaluated the effectiveness of transdermal drug delivery using sonophoresis. In skin cryosections, bFGF-loaded carboxymethyl chitosan nanocarriers delivered by ultrasound irradiation were present subcutaneously. We analyzed the bFGF content in skin tissue by ELISA and found that bFGF penetration in skin irradiated by ultrasound with nanocarriers. Penetration of bFGF-leaded carboxymethyl chitosan nanocarriers by ultrasound was significantly higher than that by ultrasound irradiation alone. Our results lay the groundwork for further utilization of polymeric nanocarriers using sonophoresis for the administration of biomacromolecules.