Chitosan/hyaluronate polyelectrolyte complexes for peptide and protein nasal delivery

Over the past decades, the nasal route of administration has gained in interest among mucosal sites, as a non-invasive alternative for systemic delivery of drugs with poor oral bioavailability, including peptide and protein drugs [1]. That is because the large surface area, porous endothelial basement membrane, high total blood flow of the nasal mucosa ensure a rapid absorption of compounds under circumvention of the hepatic first-pass metabolism. Major problems of peptide and protein nasal delivery is the mucociliary clearance mechanism and the poor ability of large molecular weight and polar molecules to cross mucosal membranes. Chitosan is gaining increasing importance in pharmaceutical applications due to its good mucoadhesion and absorption enhancing ability. Moreover, chitosan can form hydrogels able to control the rate of drug release from the delivery system as well as protect the drug from chemical and enzymatic degradation in the administration site. In particular, when chitosan is cross-linked or complexed with an oppositely charged polyelectrolyte, a three-dimensional network is formed in which the drug can be incorporated to control its release. In this work the release and permeation behaviour of insulin and vancomycin hydrochloride from mucoadhesive nasal inserts based on chitosan/hyaluronate polyelectrolyte complexes was evaluated. Nasal inserts prepared with chitosan/hyaluronate complexes obtained in different preparative conditions were characterized with respect to mucoadhesion potential, water uptake ability, drug release and permeation behaviour. [1] Illum, L. (2003) Nasal drug delivery-possibility, problems and solutions. J. Control. Release, 87, 187-198.