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
[21]   Gelation of aqueous solutions of diblock copolymers of ethylene oxide and D,L-lactide [J].
Tanodekaew, S ;
Godward, J ;
Heatley, F ;
Booth, C .
MACROMOLECULAR CHEMISTRY AND PHYSICS, 1997, 198 (11) :3385-3395
[22]   Synthesis and micelle formation of triblock copolymers of poly(methyl methacrylate)-b-poly(ethylene oxide)-b-poly(methyl methacrylate) in aqueous solution [J].
Wang, Dandan ;
Peng, Zhiping ;
Liu, Xinxing ;
Tong, Zhen ;
Wang, Chaoyang ;
Ren, Biye .
EUROPEAN POLYMER JOURNAL, 2007, 43 (07) :2799-2808
[23]   Photocrosslinked anhydride systems for long-term protein release [J].
Weiner, Ashley A. ;
Bock, Eileen A. ;
Gipson, Margaret E. ;
Shastri, V. Prasad .
BIOMATERIALS, 2008, 29 (15) :2400-2407
[24]   A subtle end-group effect on macroscopic physical gelation of triblock copolymer aqueous solutions [J].
Yu, L ;
Zhang, H ;
Ding, JD .
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION, 2006, 45 (14) :2232-2235
[25]   Injectable hydrogels as unique biomedical materials [J].
Yu, Lin ;
Ding, Jiandong .
CHEMICAL SOCIETY REVIEWS, 2008, 37 (08) :1473-1481
[26]   Injectable block copolymer hydrogels for sustained release of a PEGylated drug [J].
Yu, Lin ;
Chang, Guang Tao ;
Zhang, Huan ;
Ding, Jian Dong .
INTERNATIONAL JOURNAL OF PHARMACEUTICS, 2008, 348 (1-2) :95-106
[27]   Temperature-induced spontaneous sol-gel transitions of poly(D,L-lactic acid-co-glycolic acid)-b-poly(ethylene glycol)-b-poly(D,L-lactic acid-co-glycolic acid) triblock copolymers and their end-capped derivatives in water [J].
Yu, Lin ;
Chang, Guangtao ;
Zhang, Huan ;
Ding, Jiandong .
JOURNAL OF POLYMER SCIENCE PART A-POLYMER CHEMISTRY, 2007, 45 (06) :1122-1133
[28]   Biodegradable poly(ε-caprolactone)-poly(ethylene glycol) block copolymers:: characterization and their use as drug carriers for a controlled delivery system [J].
Zhou, SB ;
Deng, XM ;
Yang, H .
BIOMATERIALS, 2003, 24 (20) :3563-3570