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

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.