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 (Mw = 26,700) to be relatively stable in human plasma and in phosphate buffer (pH 7.4, 37 °C). Controlled release of AMB was observed in acidic phosphate buffer (pH 5.5, 37 °C) with the half-life of 2 min. The LD50 value determined in vivo (mouse) is 45 mg/kg.