Discovery of transdermal penetration enhancers by high-throughput screening
Discovery of transdermal penetration enhancers by high-throughput screening
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DOI：
10.1038/nbt928
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发表时间：
2004-02-01
影响因子：
46.9
通讯作者：
Mitragotri, S
中科院分区：
文献类型：
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作者：
Karande, P;Jain, A;Mitragotri, S
虽然经皮给药比注射给药更有吸引力，但由于皮肤渗透性低，尚未应用于大分子药物。在这里，我们描述了渗透促进剂的特定混合物，其将皮肤对大分子（~ 1 - 10 kDa）的渗透性增加高达约100倍而不诱导皮肤刺激。这些混合物的发现是通过一种实验工具实现的，即体外皮肤阻抗引导的高通量（INSIGHT）筛选，其效率比当前工具高100倍以上。体外实验表明，该混合物通过皮肤递送大分子药物，包括肝素、促黄体生成素释放激素（LHRH）和寡核苷酸。在无毛大鼠中进行的醋酸亮丙瑞林体内实验证实了月桂醇聚醚硫酸钠（SLA）和苯基哌嗪（PP）混合物的效力和安全性。这些研究显示了使用渗透促进剂从透皮贴剂全身递送大分子的可行性。
Although transdermal drug delivery is more attractive than injection, it has not been applied to macromolecules because of low skin permeability. Here we describe particular mixtures of penetration enhancers that increase skin permeability to macromolecules (-1-10 kDa) by up to similar to100-fold without inducing skin irritation. The discovery of these mixtures was enabled by an experimental tool, in vitro skin impedance guided high-throughput (INSIGHT) screening, which is >100-fold more efficient than current tools. In vitro experiments demonstrated that the mixtures delivered macromolecular drugs, including heparin, leutinizing hormone releasing hormone (LHRH) and oligonulceotides, across the skin. In vivo experiments on hairless rats with leuprolide acetate confirmed the potency and safety of one such mixture, sodium laureth sulfate (SLA) and phenyl piperazine (PP). These studies show the feasibility of using penetration enhancers for systemic delivery of macromolecules from a transdermal patch.