ABA triblock copolymers of poly(N-isopropylacrylamide-co-5,6-benzo-2-methylene -1,3-dioxepane) (A) and poly(ethylene glycol) (B): synthesis and thermogelation and degradation properties in aqueous solutions

Abstract

Novel hydrolytically degradable thermosensitive triblock copolymers with poly(ethylene glycol) (PEG) middle-chain and random copolymers of N-isopropylacrylamide and 5,6-benzo-2-methylene-1,3-dioxepane as side blocks were synthesized by the reversible addition–fragmentation chain transfer (RAFT) copolymerization of the two monomers in the presence of the bisester of [S-1-dodecyl-S′-(α,α′-dimethyl-α″-acetic acid)] trithiocarbonate and α,ω-dihydroxy PEG of 10,000 Da molecular weight as the RAFT macroagent. The polymers prepared were structurally characterized by gel permeation chromatography (GPC), 1H NMR and differential scanning calorimetry (DSC) analyses, and their thermosensitive behavior was evidenced by rheological measurements on 10 wt% aqueous solutions. The polymer aqueous solutions displayed enhanced viscosity at low temperatures due to the association of the hydrophobic dodecyl trithiocarbonate end groups, which was decreased by free radically removing the RAFT groups in the presence of tributyltin hydride. The gelation temperature, defined as the temperature at which the viscoelasticity moduli become equal each other, ranged between 36 and 43 °C depending on the aqueous solvent (distilled water or phosphate buffer saline (PBS)) and the presence of hydrophobic dodecyl end groups. The degradable character of the triblock copolymers prepared was proved by the hydrolysis of the in-chain ester groups in 1-N KOH solution at room temperature. A partial degradation of the polymer also occurred in the gel formed at 37 °C from a 10 wt% PBS solution, as proved by both GPC and 1H NMR measurements. Under these conditions, the gel completely dissolved and lost its thermogelation ability up to 60 °C in less than 24 days.