Polypeptide-based polyelectrolyte complexes overcoming the biological barriers of oral insulin delivery

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In this study, a novel oral insulin delivery system was prepared by combining two different artificial polypeptides with insulin. Negatively charged poly(L-glutamate-co-N-3-L-glutamylsulfanilic acid) (PLGS), cationic alpha helical peptide poly-L-lysine (PLL), and insulin formed polyelectrolyte complexes (PCs) were characterized. The property of the PCs was examined by an in vitro study. A significantly higher amount of the loaded FITC insulin was released in the intestinal condition, suggesting the controlled release of the PCs to protect insulin in the acidic stomach condition while releasing it in the small intestine. The in vitro cellular uptake study with Caco-2 cells also revealed the improved penetration of the loaded FITC labeled insulin. By virtue of the cell penetration enhancing ability of PLL, the permeation of insulin in the small intestine was notably augmented. Furthermore, the feasibility of the PCs was confirmed through an in vivo hypoglycemic effect study. The PCs showed an improved hypoglycemic effect suggesting the success of the delivery and penetration of the loaded insulin. The blood glucose level was lowered to 80% of its initial value after the oral administration of the PCs, and the hypoglycemia lasted for more than 14 h. The long lasting hypoglycemic effect of the PCs can reduce the number of administrations, and it will contribute to improving the quality of patients' lives. The PCs provided reasonable results as a competitive candidate for oral insulin delivery. The introduction of the PCs will promote the oral delivery of charged proteins or drugs. (C) 2017 The Korean Society of Industrial and Engineering Chemistry. Published by Elsevier B.V. All rights reserved.
Publisher
ELSEVIER SCIENCE INC
Issue Date
2017-04
Language
English
Article Type
Article
Keywords

DIABETES-MELLITUS; DRUG-DELIVERY; NANOPARTICLES; COMPLICATIONS; VESICLES; DESIGN; MODELS; MUCUS

Citation

JOURNAL OF INDUSTRIAL AND ENGINEERING CHEMISTRY, v.48, pp.79 - 87

ISSN
1226-086X
DOI
10.1016/j.jiec.2016.12.022
URI
http://hdl.handle.net/10203/223417
Appears in Collection
NT-Journal Papers(저널논문)BiS-Journal Papers(저널논문)CBE-Journal Papers(저널논문)
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