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新型聚合物环持续局部给药抑制内膜增生。

Sustained local drug delivery from a novel polymeric ring to inhibit intimal hyperplasia.

机构信息

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

出版信息

J Biomed Mater Res A. 2010 May;93(2):656-65. doi: 10.1002/jbm.a.32307.

Abstract

The long-term clinical success of autologous vein and synthetic vascular grafts are limited because of the development of anastomotic intimal hyperplasia (IH). We have previously published data suggesting that cyclosporine (CyA) may reduce the development of IH in a canine model (Hirko et al., J Vasc Surg 1993;17:877-887). However, systemic administration of CyA could create serious adverse effects. Therefore, it is our long-term goal to test the hypothesis that the controlled local release of CyA from a polymeric vascular wrap would prevent the development of IH. To test this hypothesis, we developed a controlled release polymeric ring that could be placed around anastomotic sites to deliver therapeutic drugs locally. The ring is a composite polymeric device consisting of poly(DL-lactide-co-glycolide) (PLGA) microspheres embedded in a poly(ethylene glycol) hydrogel. Several in vitro studies were conducted to evaluate the effects of different sterilization procedures on the properties of the device. It was determined that gamma sterilization was the preferred sterilization method of choice for this device. In vivo studies were conducted on a swine model to evaluate the biocompatibility of the ring. The histological findings of the ring implants at 2 and 4 weeks demonstrate the biocompatibility of this device.

摘要

自体静脉和合成血管移植物的长期临床成功受到限制,因为吻合口内膜增生(IH)的发展。我们之前发表的数据表明,环孢素(CyA)可能会减少犬模型中 IH 的发展(Hirko 等人,J Vasc Surg 1993;17:877-887)。然而,全身性给予 CyA 可能会产生严重的不良反应。因此,我们的长期目标是检验这样一个假设,即通过聚合物血管包裹物的受控局部释放 CyA 可以预防 IH 的发展。为了检验这一假设,我们开发了一种可控释放的聚合物环,可以放置在吻合部位以局部递送治疗药物。该环是一种由聚(DL-丙交酯-co-乙交酯)(PLGA)微球嵌入聚乙二醇水凝胶中组成的复合聚合物装置。进行了几项体外研究来评估不同的灭菌程序对该装置性能的影响。结果确定,伽马灭菌是该装置首选的灭菌方法。在猪模型上进行了体内研究,以评估该环的生物相容性。2 周和 4 周时的环植入物的组织学发现证明了该装置的生物相容性。

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