Optimization of phytic acid-crosslinked chitosan microspheres for oral insulin delivery using response surface methodology
- JEONG UN KIM; Hafiz Muhammad Shahbaz; Hyunah Lee; KIM TAEHYUNG; KYUNGJIK YANG; Young Hoon Roh; Jiyong Park
- Issue Date
- ELSEVIER SCIENCE BV
- Oral insulin delivery; Chitosan; Phytic acid; Ionic crosslinking; Response surface methodology
- INTERNATIONAL JOURNAL OF PHARMACEUTICS, v.588, pp.119736-1 - 119736-10
- Journal Title
- INTERNATIONAL JOURNAL OF PHARMACEUTICS
- Start Page
- End Page
- 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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- College of Life Science and Biotechnology > Biotechnology > 1. Journal Articles
- 일반대학원 > 일반대학원 생명과학부 > 1. Journal Articles
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