pH-responsive ABC type miktoarm star terpolymers: Synthesis via combination of click reaction and SET-LRP, characterization, self-assembly, and controlled drug release

- Well-defined miktoarm star terpolymers have been synthesized via one pot manner.
- Combination of click reaction and single electron transfer living radical polymerization (SET-LRP) was used.
- Terpolymers were characterized by FT-IR, H NMR, and GPC techniques.
- pH sensitivity and self-assembly behavior, cytotoxicity and hydrolytic degradation of micelles were investigated.
- Naproxen (Nap) as a model drug was incorporated in the micelles and drug release was evaluated as a function of pH.

We report on the one-pot synthesis of well-defined ABC miktoarm star terpolymers consisting of poly(ethyleneglycol)-b-poly(tert-butylacrylate)-b-polycaprolactone, (mPEG-b-PtBA-b-PCL), by using combination of click reaction and single electron transfer living radical polymerization (SET-LRP). Mono-epoxide functionalized mPEG (mPEG-EP) was synthesized and reacted with sodium azide in the presence of NH4Cl to afford mPEG-N3(-OH). Then, a difunctional molecule bearing azide and bromine moieties, mPEG-N3(-Br), was synthesized via the nucleophilic reaction of mPEG-N3(-OH) with 2-bromoisobutyryl bromide. Propargyl-terminated polycaprolactones, Prop-PCLs, were synthesized by ROP of different contents of CL using propargyl alcohol as initiator and Sn(Oct)2 as catalyst. In the presence of mPEG-N3(-Br) and mixture of Cu(0)/PMDETA/tBA, target ABC miktoarm star terpolymers mPEG-b-PtBA-b-PCL were successfully synthesized in a one-pot manner by simultaneously conducting the SET-LRP of t-butyl acrylate (tBA) and the click reaction with bromine- and azido-group of mPEG-N3(-Br), respectively. PH-sensitive terpolymers, mPEG-b-PAA-b-PCL, were prepared by selective acidolysis of tBA groups. The terpolymers were characterized by FT-IR, 1H NMR and GPC, and their pH sensitivity and self-assembly behavior were investigated by DLS and TEM techniques. Naproxen (Nap) as a model drug was incorporated in the micelles and drug release was evaluated as a function of pH. In addition, the cytotoxicity and degradation of the prepared terpolymers were also investigated.