Targeted antifungal delivery system: beta-glucosidase sensitive nystatin-star poly(ethylene glycol) conjugate

Int J Pharm. 2010 Feb 15;386(1-2):1-5. doi: 10.1016/j.ijpharm.2009.10.034. Epub 2009 Oct 27.

Abstract

A new targeted intravenous conjugate of nystatin with pentaerythritol poly(ethylene glycol)ether has been prepared and characterised (NY(4)-sPEG, M=25 160). The conjugate contains a beta-d-glucopyranoside molecular switch sensitive to beta-glucosidases (E.C.3.2.1.21), which are specifically present in the enzyme outfit of fungal pathogens. The investigated conjugate is stable under in vitro conditions for 24h (solution of phosphate buffer pH=7.4). Spectrophotometrically controlled releasing of nystatin in model medium containing beta-glucosidase ((Aspergillus niger) 2mg/mL, 66.6 units/g; pH 7.4, 2 x 10(-2)M), reported decomposition half-life of conjugate tau(1/2)=(88+/-2)s. This implies that releasing of nystatin is controlled only enzymatically.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antifungal Agents / administration & dosage
  • Antifungal Agents / chemistry*
  • Antifungal Agents / metabolism
  • Aspergillus niger / enzymology*
  • Buffers
  • Cellulases / isolation & purification
  • Cellulases / metabolism*
  • Chemistry, Pharmaceutical
  • Chromatography, Gel
  • Chromatography, High Pressure Liquid
  • Delayed-Action Preparations
  • Drug Carriers*
  • Drug Compounding
  • Drug Stability
  • Half-Life
  • Hydrogen-Ion Concentration
  • Hydrolysis
  • Kinetics
  • Magnetic Resonance Spectroscopy
  • Nystatin / administration & dosage*
  • Nystatin / chemistry
  • Nystatin / metabolism
  • Polyethylene Glycols / chemistry*
  • Propylene Glycols / chemistry*
  • Solubility
  • Spectrophotometry, Ultraviolet
  • Technology, Pharmaceutical / methods

Substances

  • Antifungal Agents
  • Buffers
  • Delayed-Action Preparations
  • Drug Carriers
  • Propylene Glycols
  • Nystatin
  • Polyethylene Glycols
  • Cellulases
  • pentaerythritol