Adelmidrol + sodium hyaluronate in IC/BPS or conditions associated to chronic urothelial inflammation. A translational study

Pharmacol Res. 2018 Aug:134:16-30. doi: 10.1016/j.phrs.2018.05.013. Epub 2018 May 22.

Abstract

Interstitial cystitis/painful bladder syndrome (IC/PBS) is a chronic bladder condition characterized by frequent urination, bladder inflammation and pain. It is a particular challenging disease and a clear unmet medical need in terms of identifying new therapeutic strategies. The aim of study was to evaluate the anti-inflammatory effects of intravesical Vessilen® (a new formulation of 2% adelmidrol (the diethanolamide derivative of azelaic acid) + 0.1% sodium hyaluronate) administration in rodent models of IC/BPS and in IC/BPS patients or other bladder disorders. Acute and chronic animal models of cystitis were induced by a single or repetitive intraperitoneal injections of cyclophosphamide (CYP); patients with IC/BPS or with bladder pain syndrome associated with symptoms of the lower urinary tract treated once weekly by bladder instillation of Vessilen® for 8 weeks. CYP instillation caused macroscopic and histological bladder alterations, inflammatory infiltrates, increased mast cell numbers, bladder pain, increased expression of nitrotyrosine, decreased expression of endothelial tight junction zonula occludens-1. Intravesical Vessilen® treatment was able to ameliorate CYP induced bladder inflammation and pain by inhibiting nuclear factor-κB pathway and inflammatory mediator levels as well as reduced mechanical allodynia and nerve growth factor levels. A significant improvement in quality of life and symptom intensity were evident in patients with IC/BPS or other bladder disorders treated with Vessilen®. Vessilen® could be a new therapeutic approach for human cystitis.

Keywords: Adelmidrol++; IC/BPS; Reactive oxygen species; Sodium hyaluronate; Sodium hyaluronate (pubchem CID:3084049); Urothelial inflammation; adelmidrol (pubchem CID: 176874).

Publication types

  • Multicenter Study
  • Observational Study

MeSH terms

  • Administration, Intravenous
  • Adult
  • Aged
  • Aged, 80 and over
  • Animals
  • Anti-Inflammatory Agents / administration & dosage*
  • Biomarkers / metabolism
  • Cystitis, Interstitial / drug therapy*
  • Cystitis, Interstitial / immunology
  • Cystitis, Interstitial / metabolism
  • Cystitis, Interstitial / pathology
  • Dicarboxylic Acids / administration & dosage*
  • Disease Models, Animal
  • Drug Combinations
  • Female
  • Fibrosis
  • Humans
  • Hyaluronic Acid / administration & dosage*
  • Inflammation Mediators / metabolism
  • Italy
  • Male
  • Mice
  • Middle Aged
  • Palmitic Acids / administration & dosage*
  • Preliminary Data
  • Rats, Sprague-Dawley
  • Time Factors
  • Treatment Outcome
  • Urothelium / drug effects*
  • Urothelium / immunology
  • Urothelium / metabolism
  • Urothelium / pathology
  • Young Adult

Substances

  • Anti-Inflammatory Agents
  • Biomarkers
  • Dicarboxylic Acids
  • Drug Combinations
  • Inflammation Mediators
  • Palmitic Acids
  • adelmidrol
  • Hyaluronic Acid