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Indexed by:期刊论文

Date of Publication:2013-03-01

Journal:MOLECULAR PHARMACEUTICS

Included Journals:SCIE、PubMed、Scopus

Volume:10

Issue:3

Page Number:951-957

ISSN No.:1543-8384

Key Words:cyclopeptide; insulin; transdermal; Caco-2 cells; enhancement activity

Abstract: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.