Chitosan as a nasal delivery system: the effect of chitosan solutions on in vitro and in vivo mucociliary transport rates in human turbinates and volunteers.

In these studies, we examined the effect on mucociliary transport rates (MTR) of various 0.25% (w/v) chitosan solutions applied to human nasal tissue both ex vivo and in vivo. In the first study a range of chitosans with different molecular weights were applied to freshly amputated human nasal turbinates, and their effect on MTR was recorded. The transient inhibitory effect on turbinate MTR that was found for most of the chitosan preparations showed a marked dependence on the volume of chitosan solution applied and the molecular weight of the chitosan tested. The higher the molecular weight of the chitosan and the more chitosan applied, the longer the original MTR was depressed. A small scale human trial, investigating the effect of chitosan glutamate, on saccharin clearance times, was also undertaken. The study showed that a once daily application of a 0.25% solution of the chitosan for 7 days had no effect on either saccharin clearance times or nasal histology as examined by light microscopy.

Measurement of nasal mucociliary transport rates on the isolated human inferior turbinate.

The mucociliary transport rate was measured using sequential images of graphite particles moving on 17 isolated human inferior turbinates. These had been removed from 13 patients who had normal saccharin clearance tests on the day of surgery. The initial mean mucociliary transport rate was found to be 4.1 mm/min rising to 5.0 mm/min 2 h after harvesting. After 4 h it fell to 3.7 mm/min. Where the rate was measured at two different sites on the same turbinate (n = 4), there was a close correlation over 6 h (r = 0.95, P < 0.001). When the turbinates were exposed to an aqueous solution of adrenaline (1:10,000) or a 2.5% cocaine solution, the rate increased or decreased respectively by 100% and 58% but returned to within 10% of the initial level within 2 h. We believe that the isolated inferior turbinate can be considered a useful model for the study of mucociliary clearance and agents that may influence it.