Thermosensitive PCL-PEG-PCL Hydrogels: Synthesis, Characterization, and Delivery of Proteins

被引:68
作者
Ma, Guilei
Miao, Bolong
Song, Cunxian [1 ]
机构
[1] Peking Union Med Coll, Tianjin Key Lab Biomat, Inst Biomed Engn, Tianjin 300192, Peoples R China
关键词
hydrogel; thermosensitive; injectable; controlled release; protein delivery; COPOLYMER AQUEOUS-SOLUTIONS; TRIBLOCK COPOLYMERS; DRUG-DELIVERY; POLY(ETHYLENE GLYCOL); RELEASE; SYSTEMS; GELATION; BEHAVIOR; ACID); WATER;
D O I
10.1002/app.31654
中图分类号
O63 [高分子化学(高聚物)];
学科分类号
070305 ; 080501 ; 081704 ;
摘要
In this work, a biodegradable and injectable in situ gel-forming controlled drug delivery system based on thermosensitive poly(epsilon-caprolactone)-poly(ethylene glycol)-poly(epsilon-caprolactone) (PCL-PEG-PCL) hydrogels was studied. A series of PCL-PEG-PCL triblock copolymers were synthesized and characterized by H-1-NMR and gel permeation chromatography (GPC). Thermosensitivity of the PCL-PEG-PCL triblock copolymers was tested using the tube inversion method. The in vitro release behaviors of two model proteins, including bovine serum albumin (BSA) and horseradish peroxidase (HRP), from PCL-PEG-PCL hydrogels were studied in detail. The in vivo gel formation and degradation of the PCL-PEG-PCL triblock copolymers were also investigated in this study. The results showed that aqueous Solutions of the synthesized PCL-PEG-PCL copolymers can form in situ gel rapidly after injection under physiological conditions. The PCL-PEG-PCL hydrogels showed the ability to control the release of incorporated BSA and HRP. The released HRP was confirmed to conserve its biological activity by specific enzymatic activity assay. The in vivo gel formation and degradation Studies indicated that PCL-PEG-PCL copolymers hydrogels can sustain at least 45 days by subcutaneous injection. Therefore, owing to great thermosensitivity and biodegradability of these copolymers, PCL-PEG-PCL copolymers hydrogels show promise as an in situ gel-forming controlled drug delivery system for therapeutic proteins. (C) 2010 Wiley Periodicals, Inc. J Appl Polym Sci 116: 1985-1993, 2010
引用
收藏
页码:1985 / 1993
页数:9
相关论文
共 28 条
[1]   Thermogelling poly(caprolactone-b-ethylene glycol-b-caprolactone) aqueous solutions [J].
Bae, SJ ;
Suh, JM ;
Sohn, YS ;
Bae, YH ;
Kim, SW ;
Jeong, B .
MACROMOLECULES, 2005, 38 (12) :5260-5265
[2]   Gelation behavior of poly(ethylene glycol) and polycaprolactone triblock and multiblock copolymer aqueous solutions [J].
Bae, Soo Jin ;
Joo, Min Kyung ;
Jeong, Yuri ;
Kim, Sung Wook ;
Lee, Woo-Kul ;
Sohn, Youn Soo ;
Jeong, Byeongmoon .
MACROMOLECULES, 2006, 39 (14) :4873-4879
[3]   Triblock copolymers: synthesis, characterization, and delivery of a model protein [J].
Chen, SB ;
Pieper, R ;
Webster, DC ;
Singh, J .
INTERNATIONAL JOURNAL OF PHARMACEUTICS, 2005, 288 (02) :207-218
[4]   Acute toxicity evaluation of in situ gel-forming controlled drug delivery system based on biodegradable poly(ε-caprolactone)-poly(ethylene glycol)-poly(ε-caprolactone) copolymer [J].
Fang, Fang ;
Gong, Chang Yang ;
Dong, Peng Wei ;
Fu, Shao Zhi ;
Gu, Ying Chun ;
Guo, Gang ;
Zhao, Xia ;
Wei, Yu Quan ;
Qian, Zhi Yong .
BIOMEDICAL MATERIALS, 2009, 4 (02)
[5]   Preparation, characterization, and drug release behaviors of drug nimodipine-loaded poly(ε-caprolactone)-poly(ethylene oxide)-poly(ε-caprolactone) amphiphilic triblock copolymer micelles [J].
Ge, HX ;
Hu, Y ;
Jiang, XQ ;
Cheng, DM ;
Yuan, YY ;
Bi, H ;
Yang, CZ .
JOURNAL OF PHARMACEUTICAL SCIENCES, 2002, 91 (06) :1463-1473
[6]   Thermosensitive PEG-PCL-PEG Hydrogel Controlled Drug Delivery System: Sol-Gel-Sol Transition and In Vitro Drug Release Study [J].
Gong, Chang Yang ;
Dong, Peng Wei ;
Shi, Shuai ;
Fu, Shao Zhi ;
Yang, Jin Liang ;
Guo, Gang ;
Zhao, Xia ;
Wei, Yu Quan ;
Qian, Zhi Yong .
JOURNAL OF PHARMACEUTICAL SCIENCES, 2009, 98 (10) :3707-3717
[7]   Synthesis and characterization of PEG-PCL-PEG thermosensitive hydrogel [J].
Gong, ChangYang ;
Shi, Shuai ;
Dong, PengWei ;
Kan, Bing ;
Gou, MaLing ;
Wang, XianHuo ;
Li, XingYi ;
Luo, Feng ;
Zhao, Xia ;
Wei, YuQuan ;
Qian, ZhiYong .
INTERNATIONAL JOURNAL OF PHARMACEUTICS, 2009, 365 (1-2) :89-99
[8]   In situ gelling stimuli-sensitive block copolymer hydrogels for drug delivery [J].
He, Chaoliang ;
Kim, Sung Wan ;
Lee, Doo Sung .
JOURNAL OF CONTROLLED RELEASE, 2008, 127 (03) :189-207
[9]   Caprolactonic poloxamer analog: PEG-PCL-PEG [J].
Hwang, MJ ;
Suh, JM ;
Bae, YH ;
Kim, SW ;
Jeong, B .
BIOMACROMOLECULES, 2005, 6 (02) :885-890
[10]   Drug release from biodegradable injectable thermosensitive hydrogel of PEG-PLGA-PEG triblock copolymers [J].
Jeong, B ;
Bae, YH ;
Kim, SW .
JOURNAL OF CONTROLLED RELEASE, 2000, 63 (1-2) :155-163