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  • Title: Synthesis and evaluation of a novel β-cyclodextrin derivative for oral insulin delivery and absorption.
    Author: Zhang L, Zhang Z, Li N, Wang N, Wang Y, Tang S, Xu L, Ren Y.
    Journal: Int J Biol Macromol; 2013 Oct; 61():494-500. PubMed ID: 23994793.
    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.
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