Effect of Cationic Cyclopeptides on Transdermal and Transmembrane Delivery of Insulin
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- 作者：Mingming Chang ; Xiaohui Li ; Yuming Sun ; Fang Cheng ; Qing Wang ; Xiaohuan Xie ; Weijie Zhao ; Xin Tian
- 刊名：Molecular Pharmaceutics
- 出版年：2013
- 出版时间：March 4, 2013
- 年：2013
- 卷：10
- 期：3
- 页码：951-957
- 全文大小：276K
- 年卷期：v.10,no.3(March 4, 2013)
- ISSN：1543-8392
文摘
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 (ACSSKKSKHCG) 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 渭mol of TD-34 in 100 渭L of saline for 8 h to diabetic rats in vivo. In addition, the transmembrane permeability in Caco-2 cell monolayers (BL鈫扐P) exhibited preferable correlation with percutaneous absorption of insulin (R2 = 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鈫扐P) might be applied to predict the percutaneous absorption of insulin chaperoned by a transdermal peptide in vivo.