Effect of Cationic Cyclopeptides on Transdermal and Transmembrane Delivery of Insulin
Effect of Cationic Cyclopeptides on Transdermal and Transmembrane Delivery of Insulin
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阳离子环肽对胰岛素透皮和跨膜递送的影响
DOI：
10.1021/mp300667p
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发表时间：
2013-03-01
影响因子：
4.9
通讯作者：
Tian, Xin
中科院分区：
文献类型：
--
作者：
Chang, Mingming;Li, Xiaohui;Tian, Xin
角质层的渗透性差限制了胰岛素穿过皮肤的运输。透皮肽对胰岛素透皮递送表现出增强活性。根据TD-1的序列，采用部分精氨酸或赖氨酸扫描的方法设计了一系列阳离子环肽（ACSSSPSKHCG）。在这些肽中，在N-5和N-6中具有双取代赖氨酸的TD-34（ACSSICKSKHCG）显示出最好的透皮促进活性，在体内将2.1IU胰岛素与0.5 μ mol TD-34的100 μ L盐水溶液一起施用给糖尿病大鼠8小时后，血糖水平降低到初始的约26%。Caco-2细胞单层的跨膜通透性（BL -> AP）与胰岛素的经皮吸收有较好的相关性（R-2 = 0.73）。结论：环肽中阳离子基团的含量和位置可以提高胰岛素的透皮吸收和跨膜能力，Caco-2细胞单层（BL -> AP）模型可以用于预测经皮肽陪伴胰岛素的体内透皮吸收。
Poor permeability of stratum corneum limits the transportation of insulin across the skin. A transdermal peptide has exhibited enhancement activity on insulin transdermal delivery. A series of cationic cyclopeptides based on the sequence of TD-1 (ACSSSPSKHCG) were designed by the partial arginine or lysine scan method. Among these peptides, TD-34 (ACSSICKSKHCG) with bis-substituted lysine in N-5 and N-6 showed the best transdermal enhancement activity, with the blood glucose level lowered to about 26% of initial after administrating 2.1 IU insulin with 0.5 mu mol of TD-34 in 100 mu L of saline for 8 h to diabetic rats in vivo. In addition, the transmembrane permeability in Caco-2 cell monolayers (BL -> AP) exhibited preferable correlation with percutaneous absorption of insulin (R-2 = 0.73). It can be concluded that the appropriate content and position of cationic group in cyclopeptides may improve percutaneous absorption and transmembrane ability of insulin, and Caco-2 cell monolayers (BL -> AP) might be applied to predict the percutaneous absorption of insulin chaperoned by a transdermal peptide in vivo.