Biodegradable and thermosensitive micelles inhibit ischemia-induced postoperative peritoneal adhesion

Qinjie Wu, Ling Li, Ning Wang, Xiang Gao, Bilan Wang, Xinyu Liu, Zhiyong Qian, Yuquan Wei, Changyang Gong State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University, Chengdu, People's Republic of China Abstract: Ischemia-induced...

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Autores principales:	Wu Q, Li L, Wang N, Gao X, Wang B, Liu X, Qian Z, Wei Y, Gong C
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2014
Materias:	Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/dc264816122849c8abd90f0b480af1aa
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spelling	oai:doaj.org-article:dc264816122849c8abd90f0b480af1aa2021-12-02T06:38:07ZBiodegradable and thermosensitive micelles inhibit ischemia-induced postoperative peritoneal adhesion1178-2013https://doaj.org/article/dc264816122849c8abd90f0b480af1aa2014-02-01T00:00:00Zhttp://www.dovepress.com/biodegradable-and-thermosensitive-micelles-inhibit-ischemia-induced-po-a15716https://doaj.org/toc/1178-2013 Qinjie Wu, Ling Li, Ning Wang, Xiang Gao, Bilan Wang, Xinyu Liu, Zhiyong Qian, Yuquan Wei, Changyang Gong State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University, Chengdu, People's Republic of China Abstract: Ischemia-induced adhesion is very common after surgery, and leads to severe abdominal adhesions. Unfortunately, many existing barrier agents used for adhesion prevention have only limited success. The objective of this study is to evaluate the efficacy of biodegradable and thermosensitive poly(ε-caprolactone)–poly(ethylene glycol)–poly(ε-caprolactone) (PCL–PEG–PCL) micelles for the prevention of postoperative ischemia-induced adhesion. We found that the synthesized PCL–PEG–PCL copolymer could self-assemble in an aqueous solution to form micelles with a mean size of 40.1±2.7 nm at 10°C, and the self-assembled micelles could instantly turn into a nonflowing gel at body temperature. In vitro cytotoxicity tests suggested that the copolymer showed little toxicity on NIH-3T3 cells even at amounts up to 1,000 µg/mL. In the in vivo test, the postsurgical ischemic-induced peritoneal adhesion model was established and then treated with the biodegradable and thermosensitive micelles. In the control group (n=12), all animals developed adhesions (mean score, 3.58±0.51), whereas three rats in the micelles-treated group (n=12) did not develop any adhesions (mean score, 0.67±0.78; P<0.001, Mann–Whitney U-test). Both hematoxylin and eosin and Masson trichrome staining of the ischemic tissues indicated that the micelles demonstrated excellent therapeutic effects on ischemia-induced adhesion. On Day 7 after micelle treatment, a layer of neo-mesothelial cells emerged on the injured tissues, which confirmed the antiadhesion effect of the micelles. The thermosensitive micelles had no significant side effects in the in vivo experiments. These results suggested that biodegradable and thermosensitive PCL–PEG–PCL micelles could serve as a potential barrier agent to reduce the severity of and even prevent the formation of ischemia-induced adhesions. Keywords: postsurgical adhesion, poly(ε-caprolactone)–poly(ethylene glycol)–poly(ε-caprolactone) (PCL–PEG–PCL), surgical complications, barrier agentWu QLi LWang NGao XWang BLiu XQian ZWei YGong CDove Medical PressarticleMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol 2014, Iss Issue 1, Pp 727-734 (2014)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine (General) R5-920
spellingShingle	Medicine (General) R5-920 Wu Q Li L Wang N Gao X Wang B Liu X Qian Z Wei Y Gong C Biodegradable and thermosensitive micelles inhibit ischemia-induced postoperative peritoneal adhesion
description	Qinjie Wu, Ling Li, Ning Wang, Xiang Gao, Bilan Wang, Xinyu Liu, Zhiyong Qian, Yuquan Wei, Changyang Gong State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University, Chengdu, People's Republic of China Abstract: Ischemia-induced adhesion is very common after surgery, and leads to severe abdominal adhesions. Unfortunately, many existing barrier agents used for adhesion prevention have only limited success. The objective of this study is to evaluate the efficacy of biodegradable and thermosensitive poly(ε-caprolactone)–poly(ethylene glycol)–poly(ε-caprolactone) (PCL–PEG–PCL) micelles for the prevention of postoperative ischemia-induced adhesion. We found that the synthesized PCL–PEG–PCL copolymer could self-assemble in an aqueous solution to form micelles with a mean size of 40.1±2.7 nm at 10°C, and the self-assembled micelles could instantly turn into a nonflowing gel at body temperature. In vitro cytotoxicity tests suggested that the copolymer showed little toxicity on NIH-3T3 cells even at amounts up to 1,000 µg/mL. In the in vivo test, the postsurgical ischemic-induced peritoneal adhesion model was established and then treated with the biodegradable and thermosensitive micelles. In the control group (n=12), all animals developed adhesions (mean score, 3.58±0.51), whereas three rats in the micelles-treated group (n=12) did not develop any adhesions (mean score, 0.67±0.78; P<0.001, Mann–Whitney U-test). Both hematoxylin and eosin and Masson trichrome staining of the ischemic tissues indicated that the micelles demonstrated excellent therapeutic effects on ischemia-induced adhesion. On Day 7 after micelle treatment, a layer of neo-mesothelial cells emerged on the injured tissues, which confirmed the antiadhesion effect of the micelles. The thermosensitive micelles had no significant side effects in the in vivo experiments. These results suggested that biodegradable and thermosensitive PCL–PEG–PCL micelles could serve as a potential barrier agent to reduce the severity of and even prevent the formation of ischemia-induced adhesions. Keywords: postsurgical adhesion, poly(ε-caprolactone)–poly(ethylene glycol)–poly(ε-caprolactone) (PCL–PEG–PCL), surgical complications, barrier agent
format	article
author	Wu Q Li L Wang N Gao X Wang B Liu X Qian Z Wei Y Gong C
author_facet	Wu Q Li L Wang N Gao X Wang B Liu X Qian Z Wei Y Gong C
author_sort	Wu Q
title	Biodegradable and thermosensitive micelles inhibit ischemia-induced postoperative peritoneal adhesion
title_short	Biodegradable and thermosensitive micelles inhibit ischemia-induced postoperative peritoneal adhesion
title_full	Biodegradable and thermosensitive micelles inhibit ischemia-induced postoperative peritoneal adhesion
title_fullStr	Biodegradable and thermosensitive micelles inhibit ischemia-induced postoperative peritoneal adhesion
title_full_unstemmed	Biodegradable and thermosensitive micelles inhibit ischemia-induced postoperative peritoneal adhesion
title_sort	biodegradable and thermosensitive micelles inhibit ischemia-induced postoperative peritoneal adhesion
publisher	Dove Medical Press
publishDate	2014
url	https://doaj.org/article/dc264816122849c8abd90f0b480af1aa
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Biodegradable and thermosensitive micelles inhibit ischemia-induced postoperative peritoneal adhesion

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