Preparation and evaluation of the in vitro drug release properties and mucoadhesion of novel microspheres of hyaluronic acid and chitosan

Rapid mucociliary clearance of intranasally administered drugs is often a key factor in determining the bioavailability of such therapeutic agents. The use of mucoadhesive microparticles provide a potential strategy for improving retention of drugs within the nasal cavity, and thereby improve the resultant pharmacokinetic profile. This study describes the comparison of a number of novel, potentially mucoadhesive microspheres, prepared by solvent evaporation, composed of hyaluronic acid (HA), chitosan glutamate (CH) and a combination of the two with microcapsules of HA and gelatin prepared by complex coacervation. The microspheres had a mean particle size of 19.91±1.57 μm (HA), 28.60±1.34 μm (HA/CH), 29.47±3.58 μm (CH). The incorporation of a model drug, gentamicin sulphate (%) was 46.90±0.53 (HA), 28.04±1.21 (HA/CH) and 13.32±1.04 (CH). The in vitro release profiles of microsphere formulations prepared by solvent evaporation were determined. The release of gentamicin from HA and HA/CH was 50% longer than CH and was best modelled as a release from a matrix. The degree of mucoadhesion of each formulation was investigated by determining the mucociliary transport rate (MTR) of the microparticles across an isolated frog palate. Acacia/gelatin microcapsules were used as a positive control. The rank order of mucoadhesion for the microspheres and the microparticles was HA=HA/CH>CH>HA/gelatin>CH ins. The entrapment of gentamicin did not affect the mucoadhesive properties ( P>0.05, Mann–Whitney U-test). The combination of HA with chitosan may afford additional advantages in combining the mucoadhesive potential of HA with the penetration enhancing effect of chitosan.