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纳米纤维介导的三碘甲状腺原氨酸持续释放:在血管生成中的作用。

Nanofiber-Mediated Sustained Delivery of Triiodothyronine: Role in Angiogenesis.

机构信息

Biological Materials Laboratory, CSIR - Central Leather Research Institute, Chennai, 600020, India.

出版信息

AAPS PharmSciTech. 2019 Feb 12;20(3):110. doi: 10.1208/s12249-019-1326-y.

Abstract

Angiogenesis is a vital component of the orchestrated wound healing cascade and tissue regeneration process, which has a therapeutic prominence in treatment of ischemic vascular diseases and certain cardiac conditions. Based on its eminence, several strategies using growth factors have been studied to initiate angiogenesis. However, growth factors are expensive and have short half-life. In this work, sustained release of triiodothyronine, which plays a crucial role in stimulating growth factors and other signaling pathways that are instrumental in initiating angiogenesis, has been attempted through electrospun polycaprolactone nanofibers. This delivery system enabled the slow and sustained delivery of triiodothyronine into the micro-environment, reducing seepage of excess into systemic circulation and eliminating the necessity of repeated dosage forms. It was observed that triiodothyronine-incorporated nanofibers exhibited favorable interaction with cells (phalloidin staining of actin filaments) and also enhanced the rate of endothelial proliferation, migration, and adhesion. The angiogenic potential of these nanofibers was further corroborated through chorioallantoic membrane and rat aortic ring assay (demonstrating cell sprouting area of 3.3 ± 0.71 mm compared to 1.2 ± 0.01 mm in control). The nanofiber matrix thus fabricated demonstrated a vibrant therapeutic potential to induce angiogenesis. Triiodothyronine also plays a significant role in wound healing independent of initiating angiogenesis. This further substantiates the positive impact of this delivery system as a dressing material for chronic wound therapeutics, ischemic vascular diseases, and certain cardiac conditions.

摘要

血管生成是协调伤口愈合级联反应和组织再生过程的重要组成部分,在治疗缺血性血管疾病和某些心脏疾病方面具有重要的治疗意义。基于其重要性,已经研究了几种使用生长因子来启动血管生成的策略。然而,生长因子昂贵且半衰期短。在这项工作中,通过静电纺丝聚己内酯纳米纤维尝试了持续释放甲状腺素,甲状腺素在刺激生长因子和其他信号通路方面起着至关重要的作用,这些信号通路对于启动血管生成至关重要。这种递药系统能够将甲状腺素缓慢且持续地递送到微环境中,减少过多的甲状腺素渗漏到体循环中,并消除对重复剂型的需求。结果表明,含有甲状腺素的纳米纤维与细胞表现出良好的相互作用(肌动蛋白丝鬼笔环肽染色),并且还增强了内皮细胞的增殖、迁移和黏附率。通过鸡胚绒毛尿囊膜和大鼠主动脉环测定进一步证实了这些纳米纤维的血管生成潜力(与对照组的 1.2 ± 0.01 mm 相比,细胞发芽面积为 3.3 ± 0.71 mm)。因此,所制备的纳米纤维基质表现出了促进血管生成的强大治疗潜力。甲状腺素在启动血管生成之外,在伤口愈合中也起着重要作用。这进一步证实了这种递药系统作为慢性伤口治疗、缺血性血管疾病和某些心脏疾病的敷料材料的积极影响。

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