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Transdermal protein delivery by a coadministered peptide identified via phage display

Nature Biotechnology volume 24, pages 455–460 (2006)Cite this article

Abstract

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 μm. 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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Figure 1: Systemic protein drug delivery mediated by TD-1.
Figure 2: Exploring TD-1's mode of action.
Figure 3: Hair follicle penetration of insulin-FITC.

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Acknowledgements

We thank Yong Chen for help on sequence analysis. This work was supported by the One Hundred Talent Project and Nanomedicine Research Project (kjcx2-sw-h12-01) of the Chinese Academy of Sciences, Anhui Talent Fund (2004Z023) and National Natural Science Foundation of China (30470871).

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Author notes

  1. Yongping Chen, Yuanyuan Shen and Xin Guo: These authors contributed equally to this work.

Authors and Affiliations

  1. Hefei National Laboratory for Physical Sciences at Microscale and School of Life Sciences, University of Science & Technology of China, Hefei, 230027, Anhui, China

    Yongping Chen, Yuanyuan Shen, Xin Guo, Caoshou Zhang, Wenjuan Yang, Minglu Ma, Shu Liu, Maobin Zhang & Long-Ping Wen

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Correspondence to Long-Ping Wen.

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Supplementary information

Supplementary Fig. 1

Inhibition of transdermal activity of PH-1 by TD-1 (PDF 67 kb)

Supplementary Fig. 2

Insulin dose response (PDF 71 kb)

Supplementary Fig. 3

Assessment of direct interaction between TD-1 and insulin (PDF 32 kb)

Supplementary Fig. 4

Time course of hair follicle penetration of insulin-FITC (PDF 142 kb)

Supplementary Fig. 5

Hair follicle penetration of TD-1 (PDF 125 kb)

Supplementary Table 1

DLS measurement (PDF 18 kb)

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Chen, Y., Shen, Y., Guo, X. et al. Transdermal protein delivery by a coadministered peptide identified via phage display. Nat Biotechnol 24, 455–460 (2006). https://doi.org/10.1038/nbt1193

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