Nature Biotechnology 24, 455 - 460 (2006)
Published online: 26 March 2006; | doi:10.1038/nbt1193
Transdermal protein delivery by a coadministered peptide identified via phage displayYongping Chen1, 2, Yuanyuan Shen1, 2, Xin Guo1, 2, Caoshou Zhang1, Wenjuan Yang1, Minglu Ma1, Shu Liu1, Maobin Zhang1
& Long-Ping Wen11
Hefei National Laboratory for Physical Sciences at Microscale and School of Life Sciences, University of Science & Technology of China, Hefei, Anhui 230027, China. 2
These authors contributed equally to this work.
Correspondence should be addressed to Long-Ping Wen lpwen@ustc.edu.cn Efficient transdermal drug delivery of large hydrophilic drugs is challenging. Here we report that the short synthetic peptide, ACSSSPSKHCG, identified by in vivo phage display, facilitated efficient transdermal protein drug delivery through intact skin. Coadministration of the peptide and insulin to the abdominal skin of diabetic rats resulted in elevated systemic levels of insulin and suppressed serum glucose levels for at least 11 h. Significant systemic bioavailability of human growth hormone was also achieved when topically coadministered with the peptide. The transdermal-enhancing activity of the peptide was sequence specific and dose dependent, did not involve direct interaction with insulin and enabled penetration of insulin into hair follicles beyond a depth of 600  m. Time-lapse studies suggested that the peptide creates a transient opening in the skin barrier to enable macromolecular drugs to reach systemic circulation.
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