Enhanced permeability of the urinary bladder wall : the role of polymer charge

The urothelium is usually impermeable to substances present in the urine. In the current work the possibility of using different absorption enhancers in the development of intravesical drug delivery systems was explored. To establish the role of the polymer charge on its ability to improve bladder wall permeability, cationic poly-L-arginine, anionic NaCMC and alginate as well as nonionic HPC and HPMC were tested. The permeability experiments were performed on isolated pig urinary bladders. We established that the charge of the polymer affects its ability to enhance the permeability of the urinary bladder wall, but to a limited extent. Positively charged polymers were the most promising absorption enhancers for the urinary bladder wall. In order to significantly enhance the permeability of the bladder wall, higher concentrations of poly-L-arginine were needed compared to chitosan. Moreover, chitosan reached the plateau of its absorption enhancement effect after 60 min, while poly-L-arginine increased the permeability continuously over 90 min. In contrast to polycarbophil, two other anionic polymers, NaCMC and alginate, did not significantly enhance the permeation of pipemidic acid into the tissue. Interactions between the polymers and the drug might prevail over the potential effect of NaCMC and alginate on tissue permeability. Furthermore, for the nonionic polymers HPMC and HPC an insignificant influence on bladder wall permeability was determined. Therefore, the selection of absorption enhancers for intravesical drug delivery systems is limited and cannot be done only on the basis of polymer charge.