Synthesis, Self-Assembly and Drug-Loading Capacity of Well-Defined Drug-Conjugated Amphiphilic A2B2 Type Miktoarm Star Copolymers Based on Poly(e-caprolactone) and Poly(ethylene glycol)

摘要

Well-defined drug-conjugated amphiphilic A2B2 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(e-caprolactone) (PCL-Br) with double hydroxyl end groups was synthesized by the CROP of e-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 NaN3 to give PCL-N3. Subsequently, the end hydroxyl groups of PCL-N3 were capped with ibuprofen as a model drug at room temperature. Finally, copper(I)-catalyzed cycloaddition reactionbetween ibuprofen-conjugated PCL-N3 and slightly excess alkyne-terminated poly- (ethylene glycol) (A-PEG) led to ibuprofen-conjugated A2B2 miktoarm star copolymer [(PCL)2-(PEG)2-D]. The excess A-PEG was removed by dialysis. 1H 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