Transdermal delivery of a ~13 kDa protein—an in vivo comparison of physical enhancement methods

Abstract

The availability of several enhancement techniques has made it possible to study delivery of macromolecules through skin. This study was conducted to evaluate the transdermal delivery of a ~13 kDa protein using iontophoresis, sonophoresis, and microneedles alone or in combination. In vivo delivery experiments were carried out using hairless rats with daniplestim (DP) as the model protein (molecular weight: 12.760 kDa; isoelectric point, 6.2). Delivery enhancement abilities of the above techniques were evaluated at two different drug concentrations in the patch: 2 mg/mL and 5 mg/mL. At a drug loading concentration of 2 mg/mL maximum delivery was seen with the combination of microneedles and iontophoresis. At 5 mg/mL, sonophoresis alone gave a C_max of 8.22 ± 5.9 ng/mL and a combination of sonophoresis and iontophoresis gave a C_max of 4.9 ± 1.8 ng/mL. The results of this study suggest that combination of microneedles and iontophoresis was the most effective approach in delivering a 13 kDa protein through the skin.

Keywords::

• Iontophoresis
• protein delivery
• microneedles
• microporation
• sonophoresis

Acknowledgments

We would like to thank Pfizer Inc., Global Biologics, Missouri (USA) for funding this project. Also, we would like to thank Pharsight Corporation (Mountain View, CA) for the academic license to WinNonlin software.