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.
|Journal||International Journal of Pharmaceutics|
|Publication status||Published - 2020 Oct 15|
Bibliographical noteFunding Information:
This research was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Science, ICT & Future Planning (No. 2014M3A7B4051898 ). This research was also supported by a grant ( 17162MFDS027 ) from the Ministry of Food and Drug Safety in 2019. The work was supported in part by Brain Korea 21 (BK21) PLUS program. K.Y. was supported by the NRF-2017-Global Ph.D. Fellowship Program.
© 2020 Elsevier B.V.
All Science Journal Classification (ASJC) codes
- Pharmaceutical Science