Synthesis, Self-Assembly and Drug-Loading Capacity of Well-Defined Drug-Conjugated Amphiphilic A2B2 Type Miktoarrn 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(epsilon-caprolactone) (PCL-Br) with double hydroxyl end groups was synthesized by the CROP of epsilon-caprolactone using 2,2-bis(bromomethyl)propane-1,3-diol as a difunctional initiator in the presence of Sn(Oct)(2) at 110 degrees C. Next, the bromide groups of PCL-Br were quantitatively converted to azide form by NaN3 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 H-1 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. (C) 2009 Wiley Periodicals, Inc J Polym Sci Part A Polym Chem 47: 6962-6976, 2009