Poly(lactic acid-co-glycolic acid)-poly(ethylene glycol)-poly(lactic acid-co-glycolic acid) thermogel as a novel submucosal cushion for endoscopic submucosal dissection

被引:83
作者
Yu, Lin [1 ]
Xu, Wei [3 ]
Shen, Wenjia [1 ]
Cao, Luping [1 ]
Liu, Yan [2 ,3 ]
Li, Zhaoshen [3 ]
Ding, Jiandong [1 ,4 ]
机构
[1] Fudan Univ, Dept Macromol Sci, Adv Mat Lab, State Key Lab Mol Engn Polymers, Shanghai 200433, Peoples R China
[2] 307 Hosp Chinese Peoples Liberat Army, Dept Gastroenterol, Beijing 100071, Peoples R China
[3] Second Mil Med Univ, Changhai Hosp, Dept Gastroenterol, Shanghai 200433, Peoples R China
[4] Fudan Univ, Sch Pharm, Key Lab Smart Drug Delivery, Minist Educ, Shanghai 201203, Peoples R China
关键词
Endoscopic submucosal dissection (ESD); Submucosal injection; Biodegradable thermogel; Perforation; Mucosal elevation; BIODEGRADABLE BLOCK-COPOLYMERS; HYALURONIC-ACID; TRIBLOCK COPOLYMER; CONTROLLED-RELEASE; SUSTAINED-RELEASE; DRUG EXENATIDE; FLUID CUSHION; PLGA BLOCK; HYDROGELS; DELIVERY;
D O I
10.1016/j.actbio.2013.12.007
中图分类号
R318 [生物医学工程];
学科分类号
0831 ;
摘要
Endoscopic submucosal dissection (ESD) is a clinical therapy for early stage neoplastic lesions in the gastrointestinal tract. It is, however, faced with a crucial problem: the high occurrence of perforation. The formation of a submucosal fluid cushion (SFC) via a fluid injection is the best way to avoid perforation, and thus an appropriate biomaterial is vital for this minimally invasive endoscopic technique. In this study, we introduced an injectable thermogel as a novel submucosal injection substance in ESD. The hydrogel synthesized by us was composed of poly(lactic acid-co-glycolic acid)-poly(ethylene glycol)-poly(lactic acid-co-glycolic acid) (PLGA-PEG-PLGA) triblock copolymers. The polymer/water system was a low-viscosity fluid at room temperature and thus easily injected, and turned into a non-flowing gel at body temperature after injection. The submucosal injection of the thermogel to create SFCs was performed in both resected porcine stomachs and living minipigs. High mucosal elevation with a clear margin was maintained for a long duration. Accurate en bloc resection was achieved with the assistance of the thermogel. The mean procedure time was strikingly reduced. Meanwhile, no obvious bleeding, perforation and tissue damage were observed. The application of the thermogel not only facilitated the ESD procedure, but also increased the efficacy and safety of ESD. Therefore, the PLGA-PEG-PLGA thermogel provides an excellent submucosal injection system, and has great potential to improve the ESD technique significantly. (C) 2013 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.
引用
收藏
页码:1251 / 1258
页数:8
相关论文
共 52 条
[1]   Sterilization, toxicity, biocompatibility and clinical applications of polylactic acid polyglycolic acid copolymers [J].
Athanasiou, KA ;
Niederauer, GG ;
Agrawal, CM .
BIOMATERIALS, 1996, 17 (02) :93-102
[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]   Comparison of properties between NIPAAm-based simultaneously physically and chemically gelling polymer systems for use in vivo [J].
Bearat, Hanin H. ;
Lee, Bae Hoon ;
Vernon, Brent L. .
ACTA BIOMATERIALIA, 2012, 8 (10) :3629-3642
[4]   Enhancement of the fraction of the active form of an antitumor drug topotecan via an injectable hydrogel [J].
Chang, Guangtao ;
Ci, Tianyuan ;
Yu, Lin ;
Ding, Jiandong .
JOURNAL OF CONTROLLED RELEASE, 2011, 156 (01) :21-27
[5]   A delicate ionizable-group effect on self-assembly and thermogelling of amphiphilic block copolymers in water [J].
Chang, Guangtao ;
Yu, Lin ;
Yang, Zigang ;
Ding, Jiandong .
POLYMER, 2009, 50 (25) :6111-6120
[6]   In situ forming hydrogels composed of oxidized high molecular weight hyaluronic acid and gelatin for nucleus pulposus regeneration [J].
Chen, Yu-Chun ;
Su, Wen-Yu ;
Yang, Shu-Hua ;
Gefen, Amit ;
Lin, Feng-Huei .
ACTA BIOMATERIALIA, 2013, 9 (02) :5181-5193
[7]   Worldwide experiences of endoscopic submucosal dissection: Not just Eastern acrobatics [J].
Cho, Kwang Bum ;
Jeon, Won Joong ;
Kim, Jae J. .
WORLD JOURNAL OF GASTROENTEROLOGY, 2011, 17 (21) :2611-2617
[8]   Injectable Block Copolymer Hydrogels: Achievements and Future Challenges for Biomedical Applications [J].
Cong Truc Huynh ;
Minh Khanh Nguyen ;
Lee, Doo Sung .
MACROMOLECULES, 2011, 44 (17) :6629-6636
[9]   Sustained delivery of doxorubicin using biodegradable pH/temperature-sensitive poly(ethylene glycol)-poly(β-amino ester urethane) multiblock copolymer hydrogels [J].
Cong Truc Huynh ;
Minh Khanh Nguyen ;
Kim, Ji Hyun ;
Kang, Seong Woo ;
Kim, Bong Sup ;
Lee, Doo Sung .
SOFT MATTER, 2011, 7 (10) :4974-4982
[10]  
Duvall A, 2007, GASTROENTEROLOGY, V132, pA417