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 (NY4-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 conjugate was tested under in vitro conditions in a solution of phosphate buffer (pH = 7.4) in which it exhibits stability for a period of 24 hours. In the model medium (beta-glucosidase (Aspergillus niger) 2 mg/ml, 66.6 units/g; pH 7.4, 2 10-2 M), the release of nystatin is controlled only enzymatically.
The controlled release of nystatin was confirmed spectrophotometrically and by means of HPLC; the decomposition half-life was τ1/2 = (88 ± 2) s.