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Optimization of phytic acid-crosslinked chitosan microspheres for oral insulin delivery using response surface methodology

Authors
JEONG UN KIMHafiz Muhammad ShahbazHyunah LeeKIM TAEHYUNGKYUNGJIK YANGYoung Hoon RohJiyong Park
Issue Date
Oct-2020
Publisher
ELSEVIER SCIENCE BV
Keywords
Oral insulin delivery; Chitosan; Phytic acid; Ionic crosslinking; Response surface methodology
Citation
INTERNATIONAL JOURNAL OF PHARMACEUTICS, v.588, pp.119736-1 - 119736-10
Journal Title
INTERNATIONAL JOURNAL OF PHARMACEUTICS
Volume
588
Start Page
119736-1
End Page
119736-10
URI
https://yscholarhub.yonsei.ac.kr/handle/2021.sw.yonsei/5306
DOI
10.1016/j.ijpharm.2020.119736
ISSN
0378-5173
Abstract
Although oral administration is favorable mode of insulin delivery, it is the most challenging route, owing to poor oral bioavailability. In this study, a chitosan (CS)-based insulin delivery system was developed by ionic crosslinking with phytic acid (PA). CS-PA microspheres were optimized with different crosslinking conditions of CS and PA using response surface methodology to retain insulin during preparation and gastric digestion. Furthermore, the in vitro release profile, morphological structure, cytotoxicity, and intestinal permeability of the optimized microspheres, and its hypoglycemic effect in diabetic rats were evaluated. Under optimal conditions, the entrapment efficiency was 97.1%, and 67.0% of insulin was retained in the microspheres after 2 h of gastric digestion followed by a sustained-release in intestinal fluid. Insulin was primarily distributed in the microsphere core with a monodisperse diameter of 663.3 μm. The microspheres increased the permeability of insulin across Caco-2/HT-29 monolayers by 1.6 times with negligible cytotoxicity. The microspheres had a relative pharmacological bioavailability of 10.6% and significantly reduced blood glucose levels with a long-lasting hypoglycemic effect after oral administration in diabetic rats. This study demonstrated that an optimized formulation of a simple ionic crosslinking system using CS and PA could facilitate efficient oral delivery of insulin.
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