Transdermal Peptide (TD 1 (peptide)), consisting of 11 amino acids, is the first transdermal enhancing peptide discovered by phage display. Transdermal Peptide binds to Na+/K+-ATPase beta-subunit (ATP1B1), and enhances the transdermal delivery of many macromolecules[1,2]. Transdermal Peptide (TD 1 (peptide))1 has been found to facilitate the transdermal delivery of many macromolecules such as botulinum neurotoxin type A (BoNT-A), growth hormone (GH), siRNA and human epidermal growth factor (hEGF) [3,4]. Energy is required for the Transdermal Peptide (TD 1 (peptide))-mediated transdermal protein delivery through rat and human skins.A novel energy-dependent permeation process during the Transdermal Peptide (TD 1 (peptide))-mediated transdermal protein delivery[7].
When ouabain was coadministered, the transdermal delivery of Transdermal Peptide (TD 1 (peptide))-hEGF, a fusion protein composed of Transdermal Peptide (TD 1 (peptide)) and hEGF, was significantly reduced. The addition of the exogenous competitor can also cause a decrease in the transdermal delivery of Transdermal Peptide (TD 1 (peptide))-hEGF. Therefore, ATP1B1 played a key role in the peptide-directed drug delivery across the skin[1].
Coadministration of Transdermal Peptide (TD 1 (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 Transdermal Peptide (TD 1 (peptide)) [2]. Blood glucose level lowered to about 26% of initial after administrating 2.1 IU insulin with 0.5 μmol of TD-34 in 100 μL of saline for 8 h to diabetic rats in vivo[6]. Transdermal Peptide (TD 1 (peptide)) delivery of anti-GAPDH siRNA significantly reduced the level of GAPDH in 72 h. Transdermal Peptide (TD 1 (peptide)) can create a transient opening in non-follicle rat skin for delivery of siRNA and reveal a novel mechanism of transdermal delivery of Transdermal Peptide (TD 1 (peptide)) and siRNA into the epidermis for gene knockdown[5].
参考文献:
[1]: Wang C, Ruan R, et,al. Role of the Na(+)/K(+)-ATPase beta-subunit in peptide-mediated transdermal drug delivery. Mol Pharm. 2015 Apr 6;12(4):1259-67. doi: 10.1021/mp500789h. Epub 2015 Mar 23. PMID: 25734358.
[2]: Chen Y, Shen Y, et,al. Transdermal protein delivery by a coadministered peptide identified via phage display. Nat Biotechnol. 2006 Apr;24(4):455-60. doi: 10.1038/nbt1193. Epub 2006 Mar 26. PMID: 16565728.
[3]: Carmichael NME, Dostrovsky JO, et,al. Peptide-mediated transdermal delivery of botulinum neurotoxin type A reduces neurogenic inflammation in the skin. Pain. 2010 May;149(2):316-324. doi: 10.1016/j.pain.2010.02.024. Epub 2010 Mar 23. PMID: 20223589.
[4]: Zhang T, Qu H, et,al. Transmembrane delivery and biological effect of human growth hormone via a phage displayed peptide in vivo and in vitro. J Pharm Sci. 2010 Dec;99(12):4880-91. doi: 10.1002/jps.22203. PMID: 20821386.
[5]: Lin CM, Huang K, et,al. A simple, noninvasive and efficient method for transdermal delivery of siRNA. Arch Dermatol Res. 2012 Mar;304(2):139-44. doi: 10.1007/s00403-011-1181-5. Epub 2011 Oct 19. PMID: 22009459.
[6]: Chang M, Li X, et,al. Effect of cationic cyclopeptides on transdermal and transmembrane delivery of insulin. Mol Pharm. 2013 Mar 4;10(3):951-7. doi: 10.1021/mp300667p. Epub 2013 Feb 21. PMID: 23391375.
[7]: Ruan R, Jin P, et,al. Peptide-chaperone-directed transdermal protein delivery requires energy. Mol Pharm. 2014 Nov 3;11(11):4015-22. doi: 10.1021/mp500277g. Epub 2014 Oct 13. PMID: 25269793.
透皮肽（TD 1（肽））由 11 个氨基酸组成，是第一个通过噬菌体展示发现的透皮增强肽。透皮肽与 Na+/K+-ATPase β-亚基 (ATP1B1) 结合，增强许多大分子的透皮递送[1,2]。透皮肽（TD 1（肽））1 已被发现可促进许多大分子的透皮递送，例如 A 型肉毒杆菌神经毒素 (BoNT-A)、生长激素 (GH)、siRNA 和人表皮生长因子 (hEGF) [3 ,4].透皮肽（TD 1（肽））介导的透皮蛋白质通过大鼠和人体皮肤递送需要能量。透皮肽（TD 1（肽））介导的透皮蛋白质递送过程中一种新型的能量依赖性渗透过程[7 .
当同时给予哇巴因时，透皮肽（TD 1（肽））-hEGF（一种由透皮肽（TD 1（肽））和 hEGF 组成的融合蛋白）的透皮递送显着降低.添加外源性竞争剂也会导致透皮肽 (TD 1 (肽))-hEGF 的透皮递送减少。因此，ATP1B1 在通过皮肤的肽导向药物递送中发挥了关键作用[1]。
透皮肽（TD 1（肽））和胰岛素共同给药至糖尿病大鼠的腹部皮肤导致全身胰岛素水平升高并抑制血清葡萄糖水平至少 11 小时。与透皮肽（TD 1（肽））[2] 局部联合给药时，人生长激素的全身生物利用度也显着提高。给予糖尿病大鼠体内 0.5 μmol TD-34 在 100 μL 生理盐水中 2.1 IU 胰岛素 8 小时后，血糖水平降至初始值的 26% 左右[6]。抗 GAPDH siRNA 的透皮肽（TD 1（肽））递送在 72 小时内显着降低了 GAPDH 的水平。透皮肽（TD 1（肽））可以在非毛囊大鼠皮肤中产生一个瞬时开口，用于递送 siRNA，并揭示一种将透皮肽（TD 1（肽））和 siRNA 经皮递送到表皮中以进行基因敲除的新机制[5].
| Kinase experiment [1]: | |
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Preparation Method |
Transdermal Peptide (TD 1 (peptide)) or ATP1B1 were incubated in 96-well plates with 0.05 M NaHCO 3 for 12 h at 4 °C. Cell lysates were incubated with fixed Transdermal Peptide (TD 1 (peptide)) for 2 h at 37°C. |
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Reaction Conditions |
0.5 mg/mL Transdermal Peptide (TD 1 (peptide)) for 2 h at 37°C. |
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Applications |
The interaction between Transdermal Peptide (TD 1 (peptide)) (0.5 mg/mL) and the full-length ATP1B1 or the C-terminus of ATP1B1 was dose-dependent. |
| Cell experiment [2]: | |
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Cell lines |
HaCaT cells |
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Preparation Method |
HaCaT cells were treated with Transdermal Peptide (TD 1 (peptide)) to study the expression of ATP1B1. |
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Reaction Conditions |
20 μg/mL Transdermal Peptide (TD 1 (peptide)) |
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Applications |
Transdermal Peptide (TD 1 (peptide)) affects the localization of ATP1B1 in HaCaT cells, ATP1B1 is initially uniformly distributed in cells, whereas after treatment with Transdermal Peptide (TD 1 (peptide)), it accumulates near the cell membrane. |
| Animal experiment [3]: | |
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Animal models |
Adult male SD rats (200 ± 10 g) |
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Preparation Method |
For in vivo skin permeation, 50 μg of Transdermal Peptide (TD 1 (peptide))-hEGF was coadministered with 500 μg of ouabain, 50 μg of GST-ATP1B1, or 50 μg of GST (control group) on the abdomen of rats for 6 h. |
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Dosage form |
50 μg Transdermal Peptide (TD 1 (peptide)) for 6h(i.p). |
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Applications |
When ouabain was coadministered, the transdermal delivery of Transdermal Peptide (TD 1 (peptide))-hEGF, a fusion protein composed of Transdermal Peptide (TD 1 (peptide)) and hEGF, was significantly reduced. The addition of the exogenous competitor can also cause a decrease in the transdermal delivery of Transdermal Peptide (TD 1 (peptide))-hEGF. Therefore, ATP1B1 played a key role in the peptide-directed drug delivery across the skin. |
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参考文献: [1].Wang C, Ruan R,et,al. Role of the Na(+)/K(+)-ATPase beta-subunit in peptide-mediated transdermal drug delivery. Mol Pharm. 2015 Apr 6;12(4):1259-67. doi: 10.1021/mp500789h. Epub 2015 Mar 23. PMID: 25734358. |
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