Drug-grafted seven-arm amphiphilic star poly(ε-caprolactone-co-carbonate)-b-poly(ethylene glycol)s based on a cyclodextrin core: synthesis and self-assembly behavior in water

Abstract

Novel well-defined drug-grafted seven-arm amphiphilic star poly(ε-caprolactone-co-carbonate)-b-poly(ethylene glycol)s based on a β-CD core [CDS-P(CL-co-DTC)-D-b-PEG] have been synthesized by the combination of controlled ring-opening polymerization (CROP), esterification coupling reactions and “click” reactions. First, 5,5-dibromomethyl-trimethylene carbonate (DBTC) bearing two bromide pendent groups was synthesized and used to copolymerize with CL to prepare seven-arm star random copolymers [CDS-P(CL-co-DBTC)] in the presence of per-2,3-acetyl-β-cyclodextrin and Sn(Oct)2. Second, esterification coupling reaction between CDS-P(CL-co-DBTC) and carboxyl-terminated mPEG led to amphiphilic seven-arm star copolymers [CDS-P(CL-co-DBTC)-b-PEG]. Subsequently, the bromide pendent groups on CDS-P(CL-co-DBTC)-b-PEG had been converted into azide groups by treating with NaN3. Finally, alkyne functionalized ibuprofen had been grafted onto the hydrophobic block of the star copolymers by copper(I)-catalyzed “click” reaction. 1H NMR, FT-IR and SEC analyses confirmed the well-defined drug grafted star architecture. These copolymers could self-assemble into multi-morphological aggregates in water, which were characterized by dynamic light scattering (DLS) and transmission electron microscopy (TEM).