Transdermal protein delivery by a coadministered peptide identified via phage display.
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 microm. Time-lapse studies suggested that the peptide creates a transient opening in the skin barrier to enable macromolecular drugs to reach systemic circulation.
Chen
Yongping
Y
Hefei National Laboratory for Physical Sciences at Microscale and School of Life Sciences, University of Science & Technology of China, Hefei, Anhui 230027, China.
Shen
Yuanyuan
Y
Guo
Xin
X
Zhang
Caoshou
C
Yang
Wenjuan
W
Ma
Minglu
M
Liu
Shu
S
Zhang
Maobin
M
Wen
Long-Ping
LP
D000287:Administration, Topical; D004337:Drug Carriers / Q000737:chemistry; D016503:Drug Delivery Systems / Q000379:methods*; D018832:Molecular Chaperones / Q000737:chemistry*; D019151:Peptide Library; D010455:Peptides / Q000737:chemistry* / Q000493:pharmacokinetics*; D011506:Proteins / Q000008:administration & dosage* / Q000737:chemistry*
D004337:Drug Carriers; D018832:Molecular Chaperones; D019151:Peptide Library; D010455:Peptides; D011506:Proteins