Synthesis, self-assembly and drug-loading capacity of well-defined drug-conjugated amphiphilic A2B2 type miktoarm star copolymers based on poly(ε-caprolactone) and poly(ethylene glycol)

Well-defined drug-conjugated amphiphilic A 2 B 2 miktoarm star copolymers [(PCL) 2 -(PEG) 2 -D] were prepared by the combination of controlled ring-opening polymerization (CROP) and “click” reaction strategy. First, bromide functionalized poly(ε-caprolactone) (PCL-Br) with double hydroxyl end groups was synthesized by the CROP of ε-caprolactone using 2,2-bis(bromomethyl)propane-1,3-diol as a difunctional initiator in the presence of Sn(Oct) 2 at 110 °C. Next, the bromide groups of PCL-Br were quantitatively converted to azide form by NaN 3 to give PCL-N 3 . Subsequently, the end hydroxyl groups of PCL-N 3 were capped with ibuprofen as a model drug at room temperature. Finally, copper(I)-catalyzed cycloaddition reaction between ibuprofen-conjugated PCL-N 3 and slightly excess alkyne-terminated poly(ethylene glycol) (A-PEG) led to ibuprofen-conjugated A 2 B 2 miktoarm star copolymer [(PCL) 2 -(PEG) 2 -D]. The excess A-PEG was removed by dialysis. 1 H NMR, FTIR and SEC analyzes confirmed the expected miktoarm star architecture. These amphiphilic miktoarm star copolymers could self-assemble into multimorphological aggregates in aqueous solution, which were characterized by dynamic light scattering (DLS) and transmission electron microscopy (TEM). In addition, the drug-loading capacity of these drug-conjugated miktoarm star copolymers as well as their nondrug-conjugated analogs were also investigated in detail. © 2009 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2009