title: 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.
authors.affiliation: Department of Organic Chemistry & Technology, Faculty of Chemical Technology, University of Pardubice, Studentská 573, 532 10 Pardubice, Czech Republic.
authors.forename: Eliska
authors.initials: E
authors.lastname: Bílková
authors.forename: Ales
authors.initials: A
authors.lastname: Imramovský
authors.forename: Vladimír
authors.initials: V
authors.lastname: Buchta
authors.forename: Milos
authors.initials: M
authors.lastname: Sedlák
mesh_terms: D000935:Antifungal Agents / Q000008:administration & dosage / Q000737:chemistry* / Q000378:metabolism; D001234:Aspergillus niger / Q000201:enzymology*; D002021:Buffers; D044602:Cellulases / Q000302:isolation & purification / Q000378:metabolism*; D002626:Chemistry, Pharmaceutical; D002850:Chromatography, Gel; D002851:Chromatography, High Pressure Liquid; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D004339:Drug Compounding; D004355:Drug Stability; D006207:Half-Life; D006863:Hydrogen-Ion Concentration; D006868:Hydrolysis; D007700:Kinetics; D009682:Magnetic Resonance Spectroscopy; D009761:Nystatin / Q000008:administration & dosage* / Q000737:chemistry / Q000378:metabolism; D011092:Polyethylene Glycols / Q000737:chemistry*; D011409:Propylene Glycols / Q000737:chemistry*; D012995:Solubility; D013056:Spectrophotometry, Ultraviolet; D013678:Technology, Pharmaceutical / Q000379:methods
chemical_list: D000935:Antifungal Agents; D002021:Buffers; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D011409:Propylene Glycols; D009761:Nystatin; D011092:Polyethylene Glycols; D044602:Cellulases; C008783:pentaerythritol