title: Synthesis and characterisation of a new pH-sensitive amphotericin B--poly(ethylene glycol)-b-poly(L-lysine) conjugate.
abstract: This paper reports on the synthesis, characterisation, and efficiency of a new intravenous conjugate of amphotericin B (AMB). Twelve molecules of AMB were attached to block copolymer poly(ethylene glycol)-b-poly(L-lysine) via pH-sensitive imine linkages. In vitro drug release studies demonstrated the conjugate (M(w)=26,700) to be relatively stable in human plasma and in phosphate buffer (pH 7.4, 37 degrees C). Controlled release of AMB was observed in acidic phosphate buffer (pH 5.5, 37 degrees C) with the half-life of 2 min. The LD(50) value determined in vivo (mouse) is 45 mg/kg.
authors.affiliation: Department of Organic Chemistry, University of Pardubice, Pardubice, Czech Republic. milos.sedlak@upce.cz
authors.forename: Milos
authors.initials: M
authors.lastname: Sedlák
authors.forename: Martin
authors.initials: M
authors.lastname: Pravda
authors.forename: Lenka
authors.initials: L
authors.lastname: Kubicová
authors.forename: Petra
authors.initials: P
authors.lastname: Mikulcíková
authors.forename: Karel
authors.initials: K
authors.lastname: Ventura
mesh_terms: D000666:Amphotericin B / Q000031:analogs & derivatives* / Q000138:chemical synthesis*; D000935:Antifungal Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D015195:Drug Design; D006863:Hydrogen-Ion Concentration; D008956:Models, Chemical; D008968:Molecular Conformation; D011092:Polyethylene Glycols / Q000737:chemistry*; D011107:Polylysine / Q000737:chemistry*; D011108:Polymers / Q000737:chemistry; D013056:Spectrophotometry, Ultraviolet / Q000379:methods; D013696:Temperature
chemical_list: D000935:Antifungal Agents; D011108:Polymers; D011107:Polylysine; D011092:Polyethylene Glycols; D000666:Amphotericin B