Degradable thermosensitive injectable hydrogels with two-phase composite structure from aqueous solutions of poly(N-isopropylacrylamide-co-5,6-benzo-2-methylene-1,3-dioxepane)—poly(ethylene glycol) triblock copolymers and biopolymers

Abstract

Novel degradable thermosensitive injectable hydrogels with two-phase composite structure and improved mechanical strength were prepared by adding sodium alginate or dextran to the aqueous solution of a hydrolytically degradable ABA triblock copolymer with poly(ethylene glycol) middle block and poly(N-isopropylacrylamide) containing in-chain ester groups as side blocks. The two-phase structure, demonstrated by SEM measurements, resulted as a consequence of the triblock copolymer-biopolymer incompatibility. The biopolymer addition decreased the gelation temperature (T gel) and strongly improved the viscoelastic properties of the resulted hydrogel, whose behavior at 37 °C turned from liquid-like to a gel-like one. The composite hydrogels displayed low gelation time and high stability (i.e., no sign of syneresis after 42 days) at 37 °C. They partially degraded in PBS at 37 °C as a consequence of the hydrolysis of the in-chain ester groups of the thermosensitive blocks, leading to a progressive increase of T gel and decrease of gel strength. The ability of the composite hydrogels to control the release rate of drugs was tested in PBS at 37 °C by employing 5-flurouracil (5FU) and chlorambucil (CLB) as model drugs with different hydrophilicity. 5FU displayed a pretty fast release rate, unlike CLB whose release rate was much slower, no effect of the biopolymer nature being noticed. During the drug release experiments, the hydrogels showed a moderate mechanical stability, although higher than in the absence of the biopolymer, and also progressively dissolved within 12–17 days because of the hydrogel erosion phenomenon, probably accelerated by the partial degradation of the triblock copolymer.