Drug development and industrial pharmacy

Heparin decreases permeability of pig urinary bladder wall preliminarily enhanced by chitosan.

PMID 18302041


Chitosan significantly increases the permeability of the isolated pig urinary bladder wall by causing urothelial desquamation, the extent of which depends also on the concentration of the polymer. By desquamation permeability barriers of the urothelium are removed. To gain additional insight into the mechanism by which chitosan acts an absorption enhancer into urinary bladder mucosa, we evaluated the influence of a polysaccharide heparin on the permeability of isolated pig urinary bladder wall preliminarily treated with chitosan. Moreover, we aimed to establish whether the effect of heparin depends on its concentration and on the degree of urothelial desquamation caused by chitosan. In the permeability studies performed by the use of diffusion cells, transport of a model drug, pipemidic acid, into the isolated pig urinary bladder wall was determined. Heparin did not have a significant effect on the permeability of the intact urothelium. When applied to the urinary bladder wall, whose permeability was preliminarily enhanced by 0.005% or 0.001% w/v chitosan, heparin decreased the permeation of pipemidic acid into the bladder wall to a level not significantly different from the intact tissue. However, the effect of heparin was not significant at the highest concentration of chitosan tested, where the damage to the urothelium was much more intense compared with that found at lower concentrations of the polymer. The formation of complexes between pipemidic acid and heparin cannot be excluded completely, but it seems that they are not the main reason for the decreased permeation of pipemidic acid in the presence of heparin. By application on the urothelium, damaged by chitosan, heparin is supposed to form a layer on the surface of the urothelium that prevents the transport of the model drug into the bladder wall. In this way heparin probably restores the impermeability properties of the urinary bladder wall to a degree dependent on the urothelial damage.

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Pipemidic acid