title: Synthesis and evaluation of a novel β-cyclodextrin derivative for oral insulin delivery and absorption.
abstract: In this paper, we describe the synthesis and testing of a novel β-cyclodextrin derivative, carboxymethy-hydroxypropyl-β-cyclodextrin (CM-HP-β-CD). After synthesis, we verified that carboxymethyl and hydroxypropyl groups were successfully substituted onto β-cyclodextrin to form CM-HP-β-CD. Then, we performed in vitro experiments to investigate (1) the ability of CM-HP-β-CD to bind insulin, (2) the transportation of insulin-CM-HP-β-CD complexes across a Caco-2 cell monolayer, and (3) the cytotoxicity of CM-HP-β-CD. CM-HP-β-CD showed the strongest insulin-binding ability and the best transport properties compared with the other β-cyclodextrin derivatives we evaluated. In addition, CM-HP-β-CD showed no cytotoxicity up to 200 mM (IC50>200 mM). To examine the effectiveness of the cyclodextrin complexes in delivering insulin in vivo, we administered different insulin-cyclodextrin complexes to diabetic rats. In these studies, we found that the insulin-CM-HP-β-CD complex provided a significant and sustained (5 h) reduction in the blood glucose levels of diabetic rats. Overall, our study showed that CM-HP-β-CD may be a promising protein carrier for use in oral protein drug delivery.
authors.affiliation: Jiangsu Key Laboratory for Supramolecular Medicinal Materials and Applications, College of Life Science, Nanjing Normal University, Nanjing 210046, China. Electronic address: lfzhang@njnu.edu.cn.
authors.forename: Liefeng
authors.initials: L
authors.lastname: Zhang
authors.forename: Zhenhai
authors.initials: Z
authors.lastname: Zhang
authors.forename: Na
authors.initials: N
authors.lastname: Li
authors.forename: Ning
authors.initials: N
authors.lastname: Wang
authors.forename: Yu
authors.initials: Y
authors.lastname: Wang
authors.forename: Shuainan
authors.initials: S
authors.lastname: Tang
authors.forename: Li
authors.initials: L
authors.lastname: Xu
authors.forename: Yong
authors.initials: Y
authors.lastname: Ren
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001786:Blood Glucose / Q000187:drug effects; D002460:Cell Line; D004337:Drug Carriers / Q000138:chemical synthesis / Q000737:chemistry*; D016503:Drug Delivery Systems; D006801:Humans; D007328:Insulin / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics / Q000633:toxicity; D008297:Male; D019906:Nuclear Magnetic Resonance, Biomolecular; D010539:Permeability; D051381:Rats; D017550:Spectroscopy, Fourier Transform Infrared; D013818:Thermogravimetry; D047392:beta-Cyclodextrins / Q000138:chemical synthesis / Q000737:chemistry*
chemical_list: D001786:Blood Glucose; D004337:Drug Carriers; D007328:Insulin; D047392:beta-Cyclodextrins
keywords: Carboxymethy-hydroxypropyl-β-cyclodextrin; Evaluation; Insulin; Synthesis