Transdermal protein delivery by a coadministered peptide identified via phage display
Transdermal protein delivery by a coadministered peptide identified via phage display
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通过噬菌体展示鉴定的共同施用的肽进行透皮蛋白质递送
DOI：
10.1038/nbt1193
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发表时间：
2006-04-01
影响因子：
46.9
通讯作者：
Wen, LP
中科院分区：
文献类型：
--
作者：
Chen, YP;Shen, YY;Wen, LP
大亲水性药物的有效透皮给药是具有挑战性的。在这里，我们报告，短的合成肽，ACSSSPSKHCG，在体内噬菌体展示，促进有效的蛋白质药物通过完整的皮肤透皮给药。在糖尿病大鼠腹部皮肤上同时给予肽和胰岛素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。当与肽局部共同给药时，也实现了人生长激素的显著全身生物利用度。该肽的透皮增强活性是序列特异性的和剂量依赖性的，不涉及与胰岛素的直接相互作用，并且能够使胰岛素渗透到超过600 μ m深度的毛囊中。延时研究表明，这种肽在皮肤屏障上产生了一个短暂的开口，使大分子药物能够到达体循环。
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 mu m. Time-lapse studies suggested that the peptide creates a transient opening in the skin barrier to enable macromolecular drugs to reach systemic circulation.