title: 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.
authors.affiliation: State Key Laboratory of Genetic Engineering, Department of Pharmaceutical Sciences, School of Life Sciences, Fudan University, Shanghai 200433, China.
authors.forename: Fuying
authors.initials: F
authors.lastname: Cui
authors.forename: Chunbai
authors.initials: C
authors.lastname: He
authors.forename: Miao
authors.initials: M
authors.lastname: He
authors.forename: Cui
authors.initials: C
authors.lastname: Tang
authors.forename: Lichen
authors.initials: L
authors.lastname: Yin
authors.forename: Feng
authors.initials: F
authors.lastname: Qian
authors.forename: Chunhua
authors.initials: C
authors.lastname: Yin
mesh_terms: D000268:Adhesiveness / Q000187:drug effects; D000278:Administration, Buccal; D000818:Animals; D001786:Blood Glucose / Q000187:drug effects; D048271:Chitosan / Q000138:chemical synthesis*; D002942:Circular Dichroism; D016503:Drug Delivery Systems; D004492:Edetic Acid / Q000138:chemical synthesis*; D005944:Glucosamine / Q000378:metabolism; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate / Q000138:chemical synthesis*; D007279:Injections, Subcutaneous; D007328:Insulin / Q000008:administration & dosage* / Q000494:pharmacology*; D008297:Male; D008855:Microscopy, Electron, Scanning; D009061:Mouth Mucosa / Q000166:cytology / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012212:Rheology / Q000187:drug effects; D017550:Spectroscopy, Fourier Transform Infrared; D014783:Viscosity / Q000187:drug effects
chemical_list: D001786:Blood Glucose; D007328:Insulin; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate; D048271:Chitosan; D004492:Edetic Acid; D005944:Glucosamine