Preparation and self-assembly of amphiphilic triblock copolymers with polyrotaxane as a middle block and their application as carrier for the controlled release of Amphotericin B

Abstract

A kind of novel amphiphilic triblock copolymers containing polyrotaxane (PR) as a central block was synthesized via the ATRP of poly(ethylene glycol) methyl ether methacrylate (PEGMA) initiated with polypseudorotaxanes made from a distal 2-bromopropionyl end-capped Pluronic F127 with a varying amount of β-CDs in the presence of Cu(I)Cl/N,N,N′,N″,N″-pentamethyldiethylenetriamine (PMDETA) at 25 °C in aqueous medium. The structure of the resulting copolymers was characterized in detail by 1H NMR, 2D ROESY NMR, GPC, DSC and WAXD analyses. The degree of polymerization of PEGMA oligomers appeared to be adjustable. As a typical sample, F-30β-CD-60 with a molar feeding ratio of Pluronic F127 to β-CD to PEGMA holding 1:30:60 was found to self-assemble into nano-sized aggregates in water. Its critical aggregation concentration was assessed by fluorescence probe technique. The corresponding hydrodynamic radius and radius of gyration were also determined by dynamic and static light scattering measurements. The transmission electron microscopy images further revealed that the sizes of the polymeric micelles of the selected copolymer were in nano-scale and smaller than those of the blank brush-like block copolymer. These nano-sized particles showed great potential to be used as carrier for the controlled release of Amphotericin B (AmB) holding 8.7% drug-loading content and 87% drug-loading efficiency with the cumulative release profile substantially longer than that of the blank brush-like block copolymer.