The use of water-soluble mucoadhesive gels for the intravesical delivery of epirubicin to the bladder for the treatment of non-muscle-invasive bladder cancer

J Pharm Pharmacol. 2015 Oct;67(10):1355-62. doi: 10.1111/jphp.12441. Epub 2015 Jun 16.

Abstract

Objectives: To develop an epirubicin-loaded, water-soluble mucoadhesive gels that have the correct rheological properties to facilitate their delivery into the bladder via a catheter, while allowing for their spread across the bladder wall with limited expansion of the bladder and increasing the retention of epirubicin in the bladder and flushing with urine.

Methods: Epirubicin-loaded hydroxyl ethyl cellulose (HEC) and hydroxy propyl methyl cellulose (HPMC) gels were manufactured and tested for their rheological properties. Their ability to be pushed through a catheter was also assessed as was their in-vitro drug release, spreading in a bladder and retention of epirubicin after flushing with simulated urine.

Key findings: Epirubicin drug release was viscosity-dependent. The 1 and 1.5% HEC gels and the 1, 1.5 and 2% HPMC gels had the correct viscosity to be administered through a model catheter and spread evenly across the bladder wall under the pressure of the detrusor muscle. The epirubicin-loaded gels had an increased retention time in the bladder when compared with a standard intravesical solution of epirubicin, even after successive flushes with simulated urine.

Conclusion: The increased retention of epirubicin in the bladder by the HEC and HPMC gels warrant further investigation, using an in-vivo model, to assess their potential for use as treatment for non-muscle-invasive bladder cancer.

Keywords: bladder cancer; epirubicin; gels; intravesical delivery; rheology.

Publication types

  • Comparative Study

MeSH terms

  • Administration, Intravesical
  • Animals
  • Antibiotics, Antineoplastic / administration & dosage
  • Antibiotics, Antineoplastic / pharmacokinetics
  • Cellulose / analogs & derivatives
  • Cellulose / chemistry
  • Drug Carriers / chemistry*
  • Drug Delivery Systems*
  • Epirubicin / administration & dosage*
  • Epirubicin / pharmacokinetics
  • Gels
  • Hypromellose Derivatives / chemistry
  • Rheology
  • Solubility
  • Swine
  • Time Factors
  • Urinary Bladder / metabolism*
  • Urinary Bladder Neoplasms / drug therapy
  • Viscosity
  • Water / chemistry

Substances

  • Antibiotics, Antineoplastic
  • Drug Carriers
  • Gels
  • Water
  • Hypromellose Derivatives
  • Epirubicin
  • Cellulose
  • hydroxyethylcellulose