Nanoparticle coatings for controlled release of quercetin from an angioplasty balloon.

Nanoparticle coatings for controlled release of quercetin from an angioplasty balloon.
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DOI:
10.1371/journal.pone.0268307
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发表时间:
2022
期刊:
影响因子:
3.7
通讯作者:
--
中科院分区:
综合性期刊3区
文献类型:
--
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外周动脉疾病(PAD)是一种腿部全身性血管疾病,导致从心脏到下肢的血流阻塞。现在是美国最常见的死亡原因之一,PAD的第一线治疗是使用气囊血管成形术机械地打开阻塞。用抗增殖剂涂覆球囊可以潜在地减少手术干预后的血管再狭窄或再狭窄,但是目前释放化疗剂(如紫杉醇)的药物涂覆球囊在某些情况下显示出长期死亡率增加。我们的目的是设计一种新型的药物涂层球囊,使用聚合物纳米递送系统持续释放多酚,减少再狭窄,但与化疗药物相比毒性降低。开发了包埋槲皮素、二甲氧基槲皮素(鼠李素)以及槲皮素共价连接至PLGA的聚(乳酸-羟基乙酸共聚物)(PLGA)纳米粒。使用超声波方法用聚合物纳米颗粒涂覆球囊导管,并测定纳米颗粒特性、载药量、涂层均匀性和药物释放。还评估了纳米颗粒与血管平滑肌细胞的粘附以及纳米递送的多酚的抗增殖作用。在测试的纳米颗粒系统中,具有共价连接的槲皮素的那些在6天的时间内提供最持续的释放。尽管与其他纳米颗粒制剂相比,这些颗粒粘附于细胞的程度较小,但它们的附着耐洗涤。这些颗粒也表现出最大的抗增殖作用。此外,当细胞在钙化条件下生长时,它们的附着没有改变,并且在PAD组织中钙化通常是阻碍药物递送的条件。此外,超声涂覆方法产生均匀的球囊涂层。因此,本文开发的具有共价连接的槲皮素的聚合物纳米颗粒系统被提出作为减少血管成形术后再狭窄的有希望的平台。
Peripheral artery disease (PAD) is a systemic vascular disease of the legs that results in a blockage of blood flow from the heart to the lower extremities. Now one of the most common causes of mortality in the U.S., the first line of therapy for PAD is to mechanically open the blockages using balloon angioplasty. Coating the balloons with antiproliferative agents can potentially reduce vessel re-narrowing, or restenosis after surgical intervention, but current drug-coated balloons releasing chemotherapy agents like paclitaxel have in some cases shown increased mortality long-term. Our aim was to design a novel drug-coated balloon using a polymeric nanodelivery system for a sustained release of polyphenols that reduce restenosis but with reduced toxicity compared to chemotherapy agents. Poly (lactic-co-glycolic acid) (PLGA) nanoparticles with entrapped quercetin, a dimethoxy quercetin (rhamnazin), as well as quercetin covalently attached to PLGA, were developed. Balloon catheters were coated with polymeric nanoparticles using an ultrasonic method, and nanoparticle characteristics, drug loading, coating uniformity and drug release were determined. The adhesion of nanoparticles to vascular smooth muscle cells and the antiproliferative effect of nano-delivered polyphenols were also assessed. Of the nanoparticle systems tested, those with covalently attached quercetin provided the most sustained release over a 6-day period. Although these particles adhered to cells to a smaller extent compared to other nanoparticle formulations, their attachment was resistant to washing. These particles also exhibited the greatest anti-proliferative effect. In addition, their attachment was not altered when the cells were grown in calcifying conditions, and in PAD tissue calcification is typically a condition that impedes drug delivery. Moreover, the ultrasonic coating method generated a uniform balloon coating. The polymeric nanoparticle system with covalently attached quercetin developed herein is thus proposed as a promising platform to reduce restenosis post-angioplasty.
DOI: 10.1161/hc3001.092037
发表时间: 2001-07-24
期刊: CIRCULATION
影响因子: 37.8
作者:
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发表时间: 2012-01
期刊: Medical science monitor : international medical journal of experimental and clinical research
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发表时间: 2020-09-01
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发表时间: 2014-08-01
影响因子: 2.9
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DOI: 10.1161/01.cir.86.1.64
发表时间: 1992-07-01
期刊: CIRCULATION
影响因子: 37.8
作者:
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