nystatin-a1 and pentaerythritol

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.

Topics: Antifungal Agents; Aspergillus niger; Buffers; Cellulases; 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; Polyethylene Glycols; Propylene Glycols; Solubility; Spectrophotometry, Ultraviolet; Technology, Pharmaceutical