Synthesis and characterization of Poloxamer 188-grafted heparin copolymer

被引:58
作者
Tian, Ji-Lai [1 ]
Zhao, Ying-Zheng [1 ]
Jin, Zhuo [1 ]
Lu, Cui-Tao [1 ]
Tang, Qin-Qin [1 ]
Xiang, Qi [2 ]
Sun, Chang-Zheng [1 ]
Zhang, Lu [1 ]
Xu, Yan-Yan [1 ]
Gao, Hui-Sheng [1 ]
Zhou, Zhi-Cai [1 ]
Li, Xiao-Kun [1 ]
Zhang, Ying [1 ]
机构
[1] Wenzhou Med Coll, Sch Pharm, Wenzhou 325035, Zhejiang, Peoples R China
[2] Jinan Univ, Biopharmaceut R&D Ctr, Guangzhou, Guangdong, Peoples R China
关键词
Critical micelle concentration; heparin; poloxamer; synthesis; temperature sensitive; FIBROBLAST-GROWTH-FACTOR; CONJUGATED POLYMERIC MICELLE; INTRAPERITONEAL INJECTION; SUSTAINED DELIVERY; RELEASE; HYDROGELS; GEL;
D O I
10.3109/03639040903520983
中图分类号
R914 [药物化学];
学科分类号
100701 ;
摘要
Background: Poloxamer 188 is a safe biocompatible polymer that can be used in protein drug delivery system. Aim: In this study, a new heparin-poloxamer 188 conjugate (HP) was synthesized and its physicochemical properties were investigated. HP structure was confirmed by Fourier transform infrared spectroscopy (FTIR) and Hydrogen-1 nuclear magnetic resonance spectroscopy (H-1-NMR). Content of the conjugated heparin was analyzed using Toluidine Blue. The critical micelle concentration (CMC) of the copolymer was determined by a fluorescence probe technique. The effect of HP on the gelation of poloxamer 188 was characterized by the rheological properties of the HP-poloxamer hydrogels. Solubility and viscosity of HP were also evaluated compared with poloxamer 188. Results: From the results, the solubility of the conjugated heparin was increased compared with free heparin. The content of heparin in HP copolymer was 62.9%. The CMC of HP and poloxamer 188 were 0.483 and 0.743 mg/mL, respectively. The gelation temperature of 0.4 g/mL HP was 43.5 degrees C, whereas that of the same concentration of poloxamer 188 was 37.3 degrees C. With HP content in poloxamer 188 solution increasing, a V-shape change of gelation temperature was observed. Conclusion: Considering the importance of poloxamer 188 in functional material, HP may prove to be a facile temperature-sensitive material for protein drug-targeted therapy.
引用
收藏
页码:832 / 838
页数:7
相关论文
共 18 条
[1]   Fundamental relationships between the composition of Pluronic block copolymers and their hypersensitization effect in MDR cancer cells [J].
Batrakova, E ;
Lee, S ;
Li, S ;
Venne, A ;
Alakhov, V ;
Kabanov, A .
PHARMACEUTICAL RESEARCH, 1999, 16 (09) :1373-1379
[2]   Injectable glycosaminoglycan hydrogels for controlled release of human basic fibroblast growth factor [J].
Cai, SS ;
Liu, YC ;
Shu, XZ ;
Prestwich, GD .
BIOMATERIALS, 2005, 26 (30) :6054-6067
[3]   Preparation of alginate/galactosylated chitosan scaffold for hepatocyte attachment [J].
Chung, TW ;
Yang, J ;
Akaike, T ;
Cho, KY ;
Nah, JW ;
Kim, SI ;
Cho, CS .
BIOMATERIALS, 2002, 23 (14) :2827-2834
[4]   The effect of heparin on the gellation of Pluronic F-127 hydrogel [J].
Chung, Yong-Il ;
Lee, Seung-Young ;
Tae, Giyoong .
COLLOIDS AND SURFACES A-PHYSICOCHEMICAL AND ENGINEERING ASPECTS, 2006, 284 (480-484) :480-484
[5]   Bone morphogenetic protein excipients: Comparative observations on poloxamer [J].
Clokie, CML ;
Urist, MR .
PLASTIC AND RECONSTRUCTIVE SURGERY, 2000, 105 (02) :628-637
[6]   Long-term and zero-order release of basic fibroblast growth factor from heparin-conjugated poly(L-lactide-co-glycolide) nanospheres and fibrin gel [J].
Jeon, O ;
Kang, SW ;
Lim, HW ;
Chung, JH ;
Kim, BS .
BIOMATERIALS, 2006, 27 (08) :1598-1607
[7]   SUSTAINED DELIVERY OF INTERLEUKIN-2 FROM A POLOXAMER-407 GEL MATRIX FOLLOWING INTRAPERITONEAL INJECTION IN MICE [J].
JOHNSTON, TP ;
PUNJABI, MA ;
FROELICH, CJ .
PHARMACEUTICAL RESEARCH, 1992, 9 (03) :425-434
[8]  
Lee J.S., 2007, CURR APPL PHYS, V7S1
[9]   Controlled dual release of basic fibroblast growth factor and indomethacin from heparin-conjugated polymeric micelle [J].
Lee, Jung Seok ;
Bae, Jin Woo ;
Joung, Yoon Ki ;
Lee, Seung Jin ;
Han, Dong Keun ;
Park, Ki Dong .
INTERNATIONAL JOURNAL OF PHARMACEUTICS, 2008, 346 (1-2) :57-63
[10]   Heparin conjugated polymeric micelle for long-terin delivery of basic fibroblast growth factor [J].
Lee, Jung Seok ;
Go, Dong Hyun ;
Bae, Jin Woo ;
Lee, Seung Jin ;
Park, Ki Dong .
JOURNAL OF CONTROLLED RELEASE, 2007, 117 (02) :204-209