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用于预防血管内膜增生的聚合物持续局部给药系统。

Polymeric sustained local drug delivery system for the prevention of vascular intimal hyperplasia.

作者信息

Kanjickal Deenu, Lopina Stephanie, Evancho-Chapman M Michelle, Schmidt Steven, Donovan Duane, Springhetti Sara

机构信息

Department of Chemical Engineering, University of Akron, Akron, Ohio 44325, USA.

出版信息

J Biomed Mater Res A. 2004 Mar 1;68(3):489-95. doi: 10.1002/jbm.a.20084.

Abstract

Anastomotic intimal hyperplasia (IH) is a major cause of both autologous vein and synthetic vascular graft failure. We have previously published data suggesting that cyclosporin may reduce the development of IH in a canine model. However, systemic administration of cyclosporin could create serious adverse effects. Therefore, it is our long-term goal to test the hypothesis that the controlled local release of cyclosporin from a polymeric vascular wrap will prevent the development of IH. To test this hypothesis, we developed a controlled release vascular wrap (sheet/ring) using a poly(ethylene glycol) (PEG) hydrogel. Sterilization of the polymers was performed using the ethylene oxide and hydrogen peroxide sterilization methods. It was found that except for one combination (8000 molecular weight and 1:1 crosslinking ratio), the differences in the swelling ratios for the sterilized and unsterilized hydrogels were not statistically significant. Release studies from unsterilized and ethylene oxide-sterilized PEG hydrogels were conducted. It was found that release lasted for approximately 50 h for sterilized as well as unsterilized PEG hydrogels. Acute animal studies, to test the deployment of both the polymeric sheets and rings to the adventitial surface of native arteries and veins, were completed successfully.

摘要

吻合口内膜增生(IH)是自体静脉和人工血管移植失败的主要原因。我们之前发表的数据表明,环孢素可能会减少犬类模型中IH的发生。然而,全身应用环孢素可能会产生严重的不良反应。因此,我们的长期目标是验证以下假设:通过聚合物血管包裹物实现环孢素的可控局部释放将预防IH的发生。为了验证这一假设,我们使用聚乙二醇(PEG)水凝胶开发了一种控释血管包裹物(片/环)。聚合物采用环氧乙烷和过氧化氢灭菌法进行灭菌。结果发现,除了一种组合(分子量8000且交联比为1:1)外,灭菌和未灭菌水凝胶的溶胀率差异无统计学意义。对未灭菌和环氧乙烷灭菌的PEG水凝胶进行了释放研究。结果发现,灭菌和未灭菌的PEG水凝胶的释放持续时间约为50小时。已成功完成急性动物研究,以测试将聚合物片和环部署到天然动脉和静脉外膜表面的情况。

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