title: Biodegradable and thermosensitive micelles inhibit ischemia-induced postoperative peritoneal adhesion.
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.
authors: State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University, Chengdu, People's Republic of China.
authors: Qinjie
authors: Q
authors: Wu
authors: State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University, Chengdu, People's Republic of China.
authors: Ling
authors: L
authors: Li
authors: State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University, Chengdu, People's Republic of China.
authors: Ning
authors: N
authors: Wang
authors: State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University, Chengdu, People's Republic of China.
authors: Xiang
authors: X
authors: Gao
authors: State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University, Chengdu, People's Republic of China.
authors: Bilan
authors: B
authors: Wang
authors: State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University, Chengdu, People's Republic of China.
authors: Xinyu
authors: X
authors: Liu
authors: State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University, Chengdu, People's Republic of China.
authors: Zhiyong
authors: Z
authors: Qian
authors: State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University, Chengdu, People's Republic of China.
authors: Yuquan
authors: Y
authors: Wei
authors: State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University, Chengdu, People's Republic of China.
authors: Changyang
authors: C
authors: Gong
mesh_terms: D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D005260:Female; D007511:Ischemia / Q000150:complications; D051379:Mice; D008823:Micelles; D041681:NIH 3T3 Cells; D050997:Nanomedicine; D010537:Peritoneum / Q000098:blood supply / Q000187:drug effects / Q000473:pathology; D011091:Polyesters / Q000008:administration & dosage / Q000633:toxicity; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000633:toxicity; D051381:Rats; D017207:Rats, Sprague-Dawley; D013696:Temperature; D000267:Tissue Adhesions / Q000473:pathology / Q000517:prevention & control*
chemical_list: D008823:Micelles; D011091:Polyesters; C515340:poly(epsilon-caprolactone)-b-poly(ethyleneglycol)-b-poly(epsilon-caprolactone); D011092:Polyethylene Glycols
keywords: poly(ε-caprolactone)–poly(ethylene glycol)–poly(ε-caprolactone) (PCL–PEG–PCL); postsurgical adhesion; surgical complications, barrier agent