New Linear and Star‐Shaped Thermogelling Poly([R]‐3‐hydroxybutyrate) Copolymers |
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Authors: | Ghislaine Barouti Dr Sing Shy Liow Dr Qingqing Dou Dr Hongye Ye Clément Orione Prof?Dr Sophie M Guillaume Prof?Dr Xian Jun Loh |
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Institution: | 1. Institut des Sciences Chimiques de Rennes, UMR 6226 CNRS, Université de Rennes 1, Campus de Beaulieu, Rennes Cedex, France;2. Institute of Materials Research and Engineering (IMRE), Singapore, Singapore;3. Centre Régional de Mesures Physiques de l'Ouest, Université de Rennes 1, Campus de Beaulieu, Rennes Cedex, France;4. Department of Materials Science and Engineering, National University of Singapore, Singapore, Singapore;5. Singapore Eye Research Institute, Singapore, Singapore |
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Abstract: | The synthesis of multi‐arm poly(R]‐3‐hydroxybutyrate) (PHB)‐based triblock copolymers (poly(R]‐3‐hydroxybutyrate)‐b‐poly(N‐isopropylacrylamide)‐b‐poly(methyl ether methacrylate)‐g‐poly(ethylene glycol)]‐co‐poly(methacrylate)‐g‐poly(propylene glycol)]], PHB‐b‐PNIPAAM‐b‐(PPEGMEMA‐co‐PPPGMA), and their subsequent self‐assembly into thermo‐responsive hydrogels is described. Atom transfer radical polymerization (ATRP) of N‐isopropylacrylamide (NIPAAM) followed by poly(ethylene glycol) methyl ether methacrylate (PEGMEMA) and poly(propylene glycol) methacrylate (PPGMA) was achieved from bromoesterified multi‐arm PHB macroinitiators. The composition of the resulting copolymers was investigated by 1H and 13C J‐MOD NMR spectroscopy as well as size‐exclusion chromatography (SEC), thermogravimetric analysis (TGA), and differential scanning calorimetry (DSC). The copolymers featuring different architectures and distinct hydrophilic/hydrophobic contents were found to self‐assemble into thermo‐responsive gels in aqueous solution. Rheological studies indicated that the linear one‐arm PHB‐based copolymer tend to form a micellar solution, whereas the two‐ and four‐arm PHB‐based copolymers afforded gels with enhanced mechanical properties and solid‐like behavior. These investigations are the first to correlate the gelation properties to the arm number of a PHB‐based copolymer. All copolymers revealed a double thermo‐responsive behavior due to the NIPAAM and PPGMA blocks, thus allowing first the copolymer self‐assembly at room temperature, and then the delivery of a drug at body temperature (37 °C). The non‐significant toxic response of the gels, as assessed by the cell viability of the CCD‐112CoN human fibroblast cell line with different concentrations of the triblock copolymers ranging from 0.03 to 1 mg mL?1, suggest that these PHB‐based thermo‐responsive gels are promising candidate biomaterials for drug‐delivery applications. |
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Keywords: | drug delivery hydrogels multi-arm polymers polyesters thermo-responsive polymers water-soluble polymers |
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