Synthesis and characterisation of a new pH-sensitive amphotericin B--poly(ethylene glycol)-b-poly(L-lysine) conjugate.
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.
Sedlák
Milos
M
Department of Organic Chemistry, University of Pardubice, Pardubice, Czech Republic. milos.sedlak@upce.cz
Pravda
Martin
M
Kubicová
Lenka
L
Mikulcíková
Petra
P
Ventura
Karel
K
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
D000935:Antifungal Agents; D011108:Polymers; D011107:Polylysine; D011092:Polyethylene Glycols; D000666:Amphotericin B