Development of a mucoadhesive nanoparticulate drug delivery system for a targeted drug release in the bladder.

PURPOSE: Purpose of the present study was the development of a mucoadhesive nanoparticulate drug delivery system for local use in intravesical therapy of interstitial cystitis, since only a small fraction of drug actually reaches the affected site by conventional treatment of bladder diseases via systemic administration.

METHODS

Chitosan-thioglycolic acid (chitosan-TGA) nanoparticles (NP) and unmodified chitosan NP were formed via ionic gelation with tripolyphosphate (TPP). Trimethoprim (TMP) was incorporated during the preparation process of NP. Thereafter, the mucoadhesive properties of NP were determined in porcine urinary bladders and the release of TMP among simulated conditions with artificial urine was evaluated.

RESULTS

The particles size ranged from 183nm to 266nm with a positive zeta potential of +7 to +13mV. Under optimized conditions the encapsulation efficiency of TMP was 37%. The adhesion of prehydrated chitosan-TGA NP on the urinary bladder mucosa under continuous urine voiding was 14-fold higher in comparison to unmodified chitosan NP. Release studies indicated a more sustained TMP release from covalently cross linked particles in comparison to unmodified chitosan-TPP NP over a period of 3h in artificial urine at 37°C.

CONCLUSION

Utilizing the method described here, chitosan-TGA NP might be a useful tool for local intravesical drug delivery in the urinary bladder.