A floating hydrogel system capable of generating CO2 bubbles to diminish urinary obstruction after intravesical instillation

Pharm Res. 2014 Oct;31(10):2655-63. doi: 10.1007/s11095-014-1362-y. Epub 2014 Apr 22.

Abstract

Aim: Intravesical instillation is commonly used to decrease the tumor recurrence after transurethral resection. However, most drug solutions would be eliminated from bladder after the first voiding of urine, so its clinical efficacy is limited. To overcome this obstacle, we developed a floating hydrogel system for controlled delivery of antitumor drugs.

Methods: The floating hydrogel was made of Adriamycin, thermo-sensitive polymer (Poloxamer 407) and NH4HCO3, which was liquid at low temperature while forming hydrogel at high temperature. Meanwhile, at high temperature, NH4HCO3 decomposed to produce CO2 bubbles, which helped hydrogel float in bladder without urinary obstruction.

Results: The mixture containing 45% P407 and 6% NH4HCO3 was selected as the optimal formulation. At 37°C, the mixture formed hydrogel and produced many bubbles which could be observed by B ultrasound. The vitro study showed that the antitumor drug Doxorubicin was released in a controlled manner. After the mixture was instilled into rabbit bladder, it formed hydrogel and floated in the bladder. The bladder stimuli was reduced and antitumor drugs could be released continuously in the bladder.

Conclusion: Our results suggested that the floating hydrogel was a feasible intravesical drug delivery system and may have application prospects in intravesical therapy for bladder cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Intravesical
  • Animals
  • Antibiotics, Antineoplastic / administration & dosage*
  • Antibiotics, Antineoplastic / therapeutic use
  • Bicarbonates / chemistry
  • Carbon Dioxide / chemistry
  • Carbon Dioxide / pharmacology*
  • Delayed-Action Preparations
  • Doxorubicin / administration & dosage*
  • Doxorubicin / therapeutic use
  • Drug Carriers / chemistry*
  • Drug Compounding
  • Drug Liberation
  • Hydrogels
  • Instillation, Drug
  • Neoplasm Recurrence, Local / prevention & control
  • Poloxamer / chemistry
  • Rabbits
  • Surface Properties
  • Temperature
  • Urethral Obstruction / etiology
  • Urethral Obstruction / prevention & control*
  • Urinary Bladder Neoplasms / surgery
  • Viscosity

Substances

  • Antibiotics, Antineoplastic
  • Bicarbonates
  • Delayed-Action Preparations
  • Drug Carriers
  • Hydrogels
  • Poloxamer
  • Carbon Dioxide
  • ammonium bicarbonate
  • Doxorubicin