Use of a Sulfated Chitosan Derivative to Reduce Bladder Inflammation in the Rat

Abstract

Objectives: Interstitial cystitis is a chronic, debilitating disease of the bladder. Treatments using intravesicular inoculation of long-chain polysaccharide formulations, such as hyaluronic acid or anti-inflammatory agents, have been used to some effect. The objective of this study was to test a long-chain polysaccharide derivative of chitosan as a vehicle for delivery of the anti-inflammatory agent 5-aminosalicylic acid (5-ASA) for treatment of inflammation in the bladder. Methods: Bladder inflammation was induced in rats by intravesicular inoculation of protamine sulfate and lipopolysaccharide. Groups of rats were randomly assigned to the treated or control groups, which received either the treatment agents or saline 24 hours after induction. The animals were killed 5 days after inoculation, and the bladders harvested for histologic examination of inflammation by a blinded observer. Four parameters of inflammation were measured using a 6-point scale. In another experiment, urinary frequency was measured 4 days after inoculation. Results: The most potent treatment agent was 3% N-sulphonato-N,O-carboxymethylchitosan plus 5-ASA, with a mean reduction in inflammation, as measured by histologic examination, of up to 75%. This level of reduction was significantly greater than that seen by treatment with the commercially available product Cystistat. In a separate experiment, 3% N-sulphonato-N,O-carboxymethylchitosan plus 5-ASA ameliorated the increase in urinary frequency seen in induced, untreated animals. Conclusions: The combination of 3% N-sulphonato-N,O-carboxymethylchitosan and 5-ASA reduced bladder inflammation as measured by histologic examination and by the lower urinary frequency. © 2007 Elsevier Inc. All rights reserved.