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Nanolayer encapsulation of insulin- chitosan complexes improves efficiency of oral insulin delivery

Authors Song L, Zhi ZL, Pickup JC

Received 12 December 2013

Accepted for publication 15 February 2014

Published 2 May 2014 Volume 2014:9(1) Pages 2127—2136

DOI https://doi.org/10.2147/IJN.S59075

Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 4

Lei Song, Zheng-liang Zhi, John C Pickup

Diabetes Research Group, King's College London School of Medicine, Guy's Hospital, London, United Kingdom

Abstract: Current oral insulin formulations reported in the literature are often associated with an unpredictable burst release of insulin in the intestine, which may increase the risk for problematic hypoglycemia. The aim of the study was to develop a solution based on a nanolayer encapsulation of insulin-chitosan complexes to afford sustained release after oral administration. Chitosan/heparin multilayer coatings were deposited onto insulin-chitosan microparticulate cores in the presence of poly(ethylene) glycol (PEG) in the precipitating and coating solutions. The addition of PEG improved insulin loading and minimized an undesirable loss of the protein resulting from redissolution. Nanolayer encapsulation and the formation of complexes enabled a superior loading capacity of insulin (>90%), as well as enhanced stability and 74% decreased solubility at acid pH in vitro, compared with nonencapsulated insulin. The capsulated insulin administered by oral gavage lowered fasting blood glucose levels by up to 50% in a sustained and dose-dependent manner and reduced postprandial glycemia in streptozotocin-induced diabetic mice without causing hypoglycemia. Nanolayer encapsulation reduced the possibility of rapid and erratic falls of blood glucose levels in animals. This technique represents a promising strategy to promote the intestinal absorption efficiency and release behavior of the hormone, potentially enabling an efficient and safe route for oral insulin delivery of insulin in diabetes management.

Keywords: oral insulin, diabetes mellitus, insulin-chitosan complexes, multilayer nanoencapsulation, polyethylene glycol, chitosan, heparin

Creative Commons License This work is published by Dove Medical Press Limited, and licensed under a Creative Commons Attribution License. The full terms of the License are available at http://creativecommons.org/licenses/by/4.0/. The license permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

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