α-Cyclodextrin and α-Cyclodextrin Polymers as Oxygen Nanocarriers to Limit Hypoxia/Reoxygenation Injury: Implications from an In Vitro Model
α-Cyclodextrin and α-Cyclodextrin Polymers as Oxygen Nanocarriers to Limit Hypoxia/Reoxygenation Injury: Implications from an In Vitro Model
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DOI：
10.3390/polym10020211
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发表时间：
2018-02-01
期刊：
影响因子：
5
通讯作者：
Trotta, Francesco
中科院分区：
文献类型：
--
作者：
Femmino, Saveria;Penna, Claudia;Trotta, Francesco
心力衰竭（HF）的发病率在全球范围内不断增加，心肌梗死（MI），缺血和再灌注（I/R）后，往往是HF发展的基础。纳米载体因其在心血管疾病中的潜在应用而成为令人感兴趣的粒子。缺血性疾病中的药物递送受损是具有挑战性的。环糊精纳米海绵（NS）可以被认为是以受控方式改善氧气输送的创新工具。这项研究开发了新的基于α-环糊精的制剂作为氧纳米载体，如天然α-环糊精（α-CD），支链α-环糊精聚合物（α-CD POLY）和α-环糊精纳米海绵（α-CD NS）。在0.2、2和20 μ g/mL下测试三种不同的基于α-CD的制剂，以确定它们在体外方案中降低缺氧和再氧合（H/R）期间细胞死亡率的能力。H9 c2是一种心肌母细胞系，暴露于常氧（20%氧气）或缺氧（5%CO2和95%N-2）。当与没有氧气的样品相比时，在缺氧之前应用的不同制剂诱导细胞死亡率的显著降低（在15%至30%的范围内）。此外，在复氧开始时应用它们可显着减少细胞死亡（12%至20%）。α-CD NS在受控氧合中显示出显著的功效，这表明聚合物系统用于MI治疗的未来医学应用的令人感兴趣的潜力。
The incidence of heart failure (HF) is increasing worldwide and myocardial infarction (MI), which follows ischemia and reperfusion (I/R), is often at the basis of HF development. Nanocarriers are interesting particles for their potential application in cardiovascular disease. Impaired drug delivery in ischemic disease is challenging. Cyclodextrin nanosponges (NS) can be considered innovative tools for improving oxygen delivery in a controlled manner. This study has developed new alpha-cyclodextrin-based formulations as oxygen nanocarriers such as native alpha-cyclodextrin (alpha-CD), branched alpha-cyclodextrin polymer (alpha-CD POLY), and alpha-cyclodextrin nanosponges (alpha-CD NS). The three different alpha-CD-based formulations were tested at 0.2, 2, and 20 mu g/mL to ascertain their capability to reduce cell mortality during hypoxia and reoxygenation (H/R) in vitro protocols. H9c2, a cardiomyoblast cell line, was exposed to normoxia (20% oxygen) or hypoxia (5% CO2 and 95% N-2). The different formulations, applied before hypoxia, induced a significant reduction in cell mortality (in a range of 15% to 30%) when compared to samples devoid of oxygen. Moreover, their application at the beginning of reoxygenation induced a considerable reduction in cell death (12% to 20%). alpha-CD NS showed a marked efficacy in controlled oxygenation, which suggests an interesting potential for future medical application of polymer systems for MI treatment.