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Biodegradable and thermosensitive micelles inhibit ischemia-induced postoperative peritoneal adhesion.

Wu Q, Li L, Wang N, Gao X, Wang B, Liu X, Qian Z, Wei Y, Gong C - Int J Nanomedicine (2014)

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: 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.

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Cytotoxicity of the micelles in vitro using MTT assay.Abbreviation: MTT, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide.
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f3-ijn-9-727: Cytotoxicity of the micelles in vitro using MTT assay.Abbreviation: MTT, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide.

Mentions: Cytotoxicity of the micelles was evaluated by cell viability assay using NIH-3T3 cells for 24 hours and 48 hours. As shown in Figure 3, with the increase of micelle concentration, viability of NIH-3T3 cells decreased accordingly at the same incubation time. With the same micelle concentration, the viability of NIH-3T3 cells decreased with incubation time increase. The cell viability was higher than 77%, even when the input micelle concentration was up to 1,000 μg/mL and incubation lasted for 48 hours. A cytotoxicity study indicated that the micelles prepared in this work were biocompatible with low cytotoxicity, which suggested that the thermosensitive micelles could be a safe antiadhesion barrier agent.


Biodegradable and thermosensitive micelles inhibit ischemia-induced postoperative peritoneal adhesion.

Wu Q, Li L, Wang N, Gao X, Wang B, Liu X, Qian Z, Wei Y, Gong C - Int J Nanomedicine (2014)

Cytotoxicity of the micelles in vitro using MTT assay.Abbreviation: MTT, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3921091&req=5

f3-ijn-9-727: Cytotoxicity of the micelles in vitro using MTT assay.Abbreviation: MTT, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide.
Mentions: Cytotoxicity of the micelles was evaluated by cell viability assay using NIH-3T3 cells for 24 hours and 48 hours. As shown in Figure 3, with the increase of micelle concentration, viability of NIH-3T3 cells decreased accordingly at the same incubation time. With the same micelle concentration, the viability of NIH-3T3 cells decreased with incubation time increase. The cell viability was higher than 77%, even when the input micelle concentration was up to 1,000 μg/mL and incubation lasted for 48 hours. A cytotoxicity study indicated that the micelles prepared in this work were biocompatible with low cytotoxicity, which suggested that the thermosensitive micelles could be a safe antiadhesion barrier agent.

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: 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.

Show MeSH
Related in: MedlinePlus