Synthesis of sharply thermo and PH responsive PMA-b-PNIPAM-b-PEG-b-PNIPAM-b-PMA by RAFT radical polymerization and its schizophrenic micellization in aqueous solutions

Abstract

Sharply thermo- and pH-responsive pentablock terpolymer with a core-shell-corona structure was prepared by RAFT polymerization of N-isopropylacrylamide and methacrylic acid monomers using PEG-based benzoate-type of RAFT agent. The PEG-based RAFT agent could be easily synthesized by dihydroxyl-capped PEG with 4-cyano-4-(thiobenzoyl) sulfanylpentanoic acids, using esterification reaction. This pentablock terpolymer was characterized by 1H NMR, FT-IR, and GPC. The PDI was obtained by GPC, indicating that the molecular weight distribution was narrow and the polymerization was well controlled. The thermo- and pH-responsive micellization of the pentablock terpolymer in aqueous solution was investigated using fluorescence spectroscopy technique, UV–vis transmittance, and TEM. The LCST of pentablock terpolymer increased (over 50 °C) compared to the NIPAM homopolymer (~32 °C), due to the incorporation of the hydrophilic PEG and PMA blocks in pentablock terpolymer (PNIPAM block as the core, PEG the block and the hydrophilic PMA block as the shell and the corona). Also, pH-dependent phase transition behavior shows at a pH value of about ~5.8, according to pKa of MAA. Thus, in acidic solution at room temperature, the pentablock terpolymer self-assembled to form core–shell–corona micelles, with the hydrophobic PMA block as the core, the PNIPAM block and the hydrophilic PEG block as the shell and the corona, respectively.

pH-Induced Amphiphilicity-Reversing Schizophrenic Aggregation by Alternating Copolymers

“…12,13 Such schizophrenic aggregation was first reported by Armes and coworkers, 14 after which a number of studies were explored during the last two decades on the reversible schizophrenic core−shell alteration of polymeric nanoaggregates, particularly in response to solution pH. 15,16 For example, the poly-(propylene oxide)-b-2-(diethylamino)ethyl methacrylate [PPO-b-PDEA] block copolymer showed schizophrenic micellization where PPO and PDEA reversibly composed the core of the micelle depending on the pH of the medium. 17 The fabrication of a three-layer "onion-like" schizophrenic micelle from the corresponding 2-(diethylamino)ethyl methacrylate-b-2-(dimethylamino)ethyl methacrylate-b-2-(N-morpholino)ethyl methacrylate [PDEA-b-PDMA-b-PMEMA] triblock copolymer was also reported where PDEA and PMEMA blocks successively participated in hydrophobic core formation.…”

Thermo/pH dual-responsive micelles based on the host–guest interaction between benzimidazole-terminated graft copolymer and β-cyclodextrin-functionalized star block copolymer for smart drug delivery

“…It can be seen that the micelles displayed a significant increase in transmittance at ca. pH 5.5, which was very near to the pKa of PMAA units (about 5.6 [ 67 , 68 ]). At pH below the pK a value (5.5), PMAA exhibits a marked pH-induced conformational transition, and owing to the formation of aggregates of the hydrophobic segments after the disassociation of the inclusion complexes, the transmittance had relatively lower values, being in accordance with the previously reported studies [ 68 , 69 ].…”

Synthetic Methodologies for Chelating Polymer Ligands: Recent Advances and Future Development

“…PEG‐based benzoate‐type of RAFT agent, where PEG is poly(ethylene glycol), was used in the preparation of a pentablock terpolymer with a core‐shell‐corona structure by RAFT polymerization of monomers of N‐isopropylacrylamide (NIPAM) and methacrylic acid (MAA) (Scheme ) . The resulting polymer has the narrow molecular weight distribution and self‐assembles to form core‐shell‐corona micelles with a hydrophobic PMAA block as a core, a PNIPAM block as a shell and a PEG hydrophilic block as a corona.…”