title: Effect of cationic cyclopeptides on transdermal and transmembrane delivery of insulin.
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 (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 μmol of TD-34 in 100 μL 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.
authors: School of Pharmaceutical Science and Technology, Dalian University of Technology , 2 Linggong Road, Dalian, Liaoning 116024, China.
authors: Mingming
authors: M
authors: Chang
authors: Xiaohui
authors: X
authors: Li
authors: Yuming
authors: Y
authors: Sun
authors: Fang
authors: F
authors: Cheng
authors: Qing
authors: Q
authors: Wang
authors: Xiaohuan
authors: X
authors: Xie
authors: Weijie
authors: W
authors: Zhao
authors: Xin
authors: X
authors: Tian
mesh_terms: D000279:Administration, Cutaneous; D000818:Animals; D018938:Caco-2 Cells; D002470:Cell Survival / Q000187:drug effects; D016503:Drug Delivery Systems / Q000379:methods; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D066298:In Vitro Techniques; D007328:Insulin / Q000008:administration & dosage* / Q000493:pharmacokinetics; D008297:Male; D018613:Microscopy, Confocal; D010455:Peptides / Q000008:administration & dosage / Q000009:adverse effects / Q000138:chemical synthesis / Q000737:chemistry; D051381:Rats; D012867:Skin / Q000378:metabolism
chemical_list: D007004:Hypoglycemic Agents; D007328:Insulin; D010455:Peptides