Preparation of injectable and thermoresponsive hydrogel based on penta-block copolymer with improved sol stability and mechanical properties

New biocompatible, biodegradable and thermosensitive penta-block copolymer poly (N-isopropylacrylamide)–b-poly (ε-caprolactone)–b-poly ethylene glycol–b-poly (ε-caprolactone)–b-poly (N-isopropylacrylamide) (PNIPAAm–PCL–PEG–PCL–PNIPAAm) was synthesized by a combination of controlled ring-opening polymerization (ROP) and atom transfer radical polymerization (ATRP). This penta-block copolymer undergoes reversible sol–gel transitions between room temperature (22 °C) and human body temperature (37 °C). By incorporation of poly (N-isopropylacrylamide) (PNIPAAm) block at the end of PCL–PEG–PCL (PCEC) triblock copolymer, the resulting PNIPAAm–PCEC–PNIPAAm penta-block copolymer achieves improved mechanical properties and high sol stability while keeping its thermogelling property in the range of physiological temperatures 20–50 °C. The mechanical properties of these materials as a function of temperature were measured by rheometry. To confirm the sol stability, the crystalizability of penta-block copolymer was analyzed by the XRD. The sol-to-gel transition temperature of block copolymer aqueous solution is controllable by varying the composition and molecular weight of PEG and PNIPAAm. Their physicochemical properties in aqueous media were characterized by 1H NMR spectroscopy and GPC techniques. This amphiphilic copolymer is self-assembled into spherical micelles in aqueous solution at room temperature. The critical micelle concentration (CMC) of these amphiphilic block copolymers was studied by fluorescence techniques. The size distribution and thermal responses of the polymeric micelles and aggregation to hydrogel in higher temperature were investigated by dynamic light scattering (DLS). The synthesized copolymer showed no apparent cytotoxicity on normal cells. In vitro release studies showed that the anticancer agent Na-HCl is effectively loaded and released by the temperature sensitive PNIPAAm–PCEC–PNIPAAm penta-block copolymer.