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Chitosan in 0.5% w/v concentration enhanced the permeability of the isolated pig urinary bladder wall by desquamation of the urothelium as ascertained in our previous study. The aim of the present work was to determine the time and concentration dependence of chitosan's effect on the permeation of a model drug into the bladder wall and to establish if the mechanism of permeation enhancement depends on the concentration of chitosan used. In the permeability studies performed by the use of diffusion cells, transport of a model drug moxifloxacin into the isolated pig urinary bladder wall was determined. For morphological observations of the urothelium in response to chitosan treatment scanning and transmission electron microscopy were applied. Within 90 min the effect of chitosan on the tissue amounts of moxifloxacin gradually increased and approached its plateau. In one hour even 0.0005% w/v dispersion of chitosan significantly enhanced the permeability of the pig urinary bladder wall for the model drug and at 0.001% w/v concentration the maximal effect on the tissue permeability was achieved. All concentrations of chitosan that significantly enhanced the permeability of the bladder wall triggered necrosis of superficial cells or desquamation of the urothelium. However, at lower concentrations and shorter exposure times the damage of the urothelium was limited to the changes in tight junctions. Chitosan was ascertained to increase the permeation of moxifloxacin into the urinary bladder wall in a time and concentration dependent manner.

Permeability of Pig Urinary Bladder Wall: Time and Concentration Dependent Effect of Chitosan