Microwave-assisted synthesis of thermo- and pH-responsive antitumor drug carrier through reversible addition–fragmentation chain transfer polymerization

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This paper reports the rapid synthesis of a dual-responsive copolymer through reversible addition-fragmentation chain transfer (RAFT) polymerization under microwave irradiation.Through use of 2-ethoxycarbonothioylthio acetic acid (ECTA) as a RAFT agent, the microwave-assisted polymerization rate of N-isopropylacrylamide (NIPAM) was approximately 150 times faster than that observed under conventional heating conditions, and the resulting homopolymer can be reactivated as a macroinitiator to produce poly(N-isopropylacrylamide-block-methacrylic acid) (PNIPAM-b-PMAA) block copolymers through a similar method.Research into the detailed polymerization kinetics of the PNIPAM and PNIPAM-b-PMAA revealed living characteristics that included a linear relationship between M n and conversion, controlled molecular weights, and a relatively narrow molecular weight distribution.The solution of the block copolymers in phosphate-buffered saline buffer displayed a phase transition at a lower critical solution temperature transition of 42 °C, and altering the pH from 7 to 3.5 resulted in various degrees of polymer aggregation in the solution.Cisplatin was loaded to the polymeric carrier through a ligand exchange to form a macromolecular prodrug.The observed critical micelle concentration was 0.25 mg/mL.Overall, these polymers offer considerable potential for developing a new multifunctional drug delivery system.

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