New Linear and Star-Shaped Thermogelling Poly([R]-3-hydroxybutyrate) Copolymers

被引:81
作者
Barouti, Ghislaine [1 ,2 ]
Liow, Sing Shy [2 ]
Dou, Qingqing [2 ]
Ye, Hongye [2 ]
Orione, Clement [3 ]
Guillaume, Sophie M. [1 ]
Loh, Xian Jun [2 ,4 ,5 ]
机构
[1] Univ Rennes 1, Inst Sci Chim Rennes, CNRS, UMR 6226, Campus Beaulieu 263 Ave Gen Leclerc, F-35042 Rennes, France
[2] Inst Mat Res & Engn, 3 Res Link, Singapore 117602, Singapore
[3] Univ Rennes 1, Ctr Reg Mesures Phys Ouest, Campus Beaulieu 263 Ave Gen Leclerc, F-35042 Rennes, France
[4] Natl Univ Singapore, Dept Mat Sci & Engn, 9 Engn Dr 1, Singapore 117576, Singapore
[5] Singapore Eye Res Inst, 11 Third Hosp Ave, Singapore 168751, Singapore
关键词
drug delivery; hydrogels; multi-arm polymers; polyesters; thermo-responsive polymers; water-soluble polymers; POLY(ETHYLENE GLYCOL); BLOCK-COPOLYMERS; THERMOSENSITIVE HYDROGEL; N-ISOPROPYLACRYLAMIDE; TRIBLOCK COPOLYMERS; PROTEIN RELEASE; GELATION; POLY(N-ISOPROPYLACRYLAMIDE); MICELLIZATION; DEGRADATION;
D O I
10.1002/chem.201601404
中图分类号
O6 [化学];
学科分类号
070301 [无机化学];
摘要
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 H-1 and C-13 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 degrees 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 1mgmL(-1), suggest that these PHB-based thermo-responsive gels are promising candidate biomaterials for drug-delivery applications.
引用
收藏
页码:10501 / 10512
页数:12
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