title: New Linear and Star-Shaped Thermogelling Poly([R]-3-hydroxybutyrate) Copolymers.
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 (1) H and (13) C 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.
authors.affiliation: Institut des Sciences Chimiques de Rennes, UMR 6226 CNRS, Université de Rennes 1, Campus de Beaulieu, 263 Avenue du Général Leclerc, 35042, Rennes Cedex, France.|Institute of Materials Research and Engineering (IMRE), 3 Research Link, Singapore, 117602, Singapore.
authors.forename: Ghislaine
authors.initials: G
authors.lastname: Barouti
authors.affiliation: Institute of Materials Research and Engineering (IMRE), 3 Research Link, Singapore, 117602, Singapore.
authors.forename: Sing Shy
authors.initials: SS
authors.lastname: Liow
authors.affiliation: Institute of Materials Research and Engineering (IMRE), 3 Research Link, Singapore, 117602, Singapore.
authors.forename: Qingqing
authors.initials: Q
authors.lastname: Dou
authors.affiliation: Institute of Materials Research and Engineering (IMRE), 3 Research Link, Singapore, 117602, Singapore.
authors.forename: Hongye
authors.initials: H
authors.lastname: Ye
authors.affiliation: Centre Régional de Mesures Physiques de l'Ouest, Université de Rennes 1, Campus de Beaulieu, 263 Avenue du Général Leclerc, 35042, Rennes Cedex, France.
authors.forename: Clément
authors.initials: C
authors.lastname: Orione
authors.affiliation: Institut des Sciences Chimiques de Rennes, UMR 6226 CNRS, Université de Rennes 1, Campus de Beaulieu, 263 Avenue du Général Leclerc, 35042, Rennes Cedex, France. sophie.guillaume@univ-rennes1.fr.
authors.forename: Sophie M
authors.initials: SM
authors.lastname: Guillaume
authors.affiliation: Institute of Materials Research and Engineering (IMRE), 3 Research Link, Singapore, 117602, Singapore. lohxj@imre.a-star.edu.sg.|Department of Materials Science and Engineering, National University of Singapore, 9 Engineering Drive 1, Singapore, 117576, Singapore. lohxj@imre.a-star.edu.sg.|Singapore Eye Research Institute, 11 Third Hospital Avenue, Singapore, 168751, Singapore. lohxj@imre.a-star.edu.sg.
authors.forename: Xian Jun
authors.initials: XJ
authors.lastname: Loh
mesh_terms: D000180:Acrylic Resins / Q000737:chemistry; D002460:Cell Line; D002470:Cell Survival; D004317:Doxorubicin / Q000737:chemistry; D004337:Drug Carriers / Q000737:chemistry; D065546:Drug Liberation; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects; D006801:Humans; D020100:Hydrogels / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity; D057927:Hydrophobic and Hydrophilic Interactions; D006885:Hydroxybutyrates / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity; D008689:Methacrylates / Q000737:chemistry; D008823:Micelles; D015394:Molecular Structure; D011091:Polyesters / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity; D011092:Polyethylene Glycols / Q000737:chemistry; D058105:Polymerization; D011108:Polymers / Q000737:chemistry; D011109:Polymethacrylic Acids / Q000737:chemistry; D000091402:Prohibitins; D011409:Propylene Glycols / Q000737:chemistry; D013696:Temperature; D000094122:Polyhydroxybutyrates
chemical_list: D000180:Acrylic Resins; D004317:Doxorubicin; D004337:Drug Carriers; D020100:Hydrogels; D006885:Hydroxybutyrates; D008689:Methacrylates; D008823:Micelles; D011091:Polyesters; D011092:Polyethylene Glycols; D011108:Polymers; D011109:Polymethacrylic Acids; D000091402:Prohibitins; D011409:Propylene Glycols; C000717328:PHB protein, human; C524499:polyethylene glycol methacrylate; C030613:polymethacrylic acid; C052970:poly-N-isopropylacrylamide; C012504:polypropylene glycol; C003182:poly-beta-hydroxybutyrate; D000094122:Polyhydroxybutyrates
keywords: drug delivery; hydrogels; multi-arm polymers; polyesters; thermo-responsive polymers; water-soluble polymers