Preparation and evaluation of chitosan-ethylenediaminetetraacetic acid hydrogel films for the mucoadhesive transbuccal delivery of insulin.

Abstract

This manuscript describes the development of a new porous, flexible bilaminated film for buccal protein administration by a simple and mild casting procedure. It consists of a mucoadhesive layer (chitosan-ethylenediaminetetraacetic acid hydrogel film) containing protein drugs and an impermeable protective layer made of ethylcellose. The obtained mucoadhesive layer was characterized in terms of Fourier transform infrared spectroscopy, rheology, swelling, and mucoadhesion. Rheology results showed that chitosan-ethylenediaminetetraacetic acid hydrogel (10:2) possessed the greatest degree of viscoelasticity and was well-structured compared with other hydrogels. The in vitro mucoadhesion studies also showed that the mucoadhesive force of the hydrogel remained over 17,000 N/m2 during 4 h in the simulated oral cavity. The insulin loaded bilaminated film showed a pronounced hypoglycemic effect following buccal administration to healthy rats, achieving a 17% pharmacological availability compared with subcutaneous insulin injection. According to these results, the bilaminated film would be a promising delivery carrier for protein drugs via the buccal route.