α-Cyclodextrin and α-Cyclodextrin Polymers as Oxygen Nanocarriers to Limit Hypoxia/Reoxygenation Injury: Implications from an In Vitro Model

Abstract

Abstract: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 α-cyclodextrin-based formulations as oxygen nanocarriers such as native α-cyclodextrin (α-CD), branched α-cyclodextrin polymer (α-CD POLY), and α-cyclodextrin nanosponges (α-CD NS). The three different α-CD-based formulations were tested at 0.2, 2, and 20 µg/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% CO 2 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%). α-CD NS showed a marked efficacy in controlled oxygenation, which suggests an interesting potential for future medical application of polymer systems for MI treatment.

Retracted Article: Long noncoding RNA ANRIL protects cardiomyocytes against hypoxia/reoxygenation injury by sponging miR-195-5p and upregulating Bcl-2

“…It is widely acknowledged that H/R is a hazardous factor, resulting in myocardial apoptosis and necrosis, which are two key cellular events in AMI. 2,20 In the present study, our data supported that H/R induced myocardial cell injury, as evidenced by the repression of cell proliferation and the promotion of cell apoptosis, in accordance with previous studies. 25,26 Subsequently, we further explored the effect and underlying mechanism of ANRIL on AMI by H/Rinduced myocardial cells.…”

Overcoming the Limits of Flash Nanoprecipitation: Effective Loading of Hydrophilic Drug into Polymeric Nanoparticles with Controlled Structure

“…The production of nanocarriers is one the most innovative and promising research fields in modern pharmaceutical technology: As a matter of fact, the use of nanoscale formulations can improve drug compatibility [1,2], provide more accurate diagnosis [3,4], reduce the risk of immune response [5,6], and achieve targeted drug delivery [7,8]. Despite the aforementioned scientific advancements, the market of nanoscale medical devices is still a niche one, not only because of regulatory issues, but also because of the difficulties encountered in producing nanocarriers at an industrial scale [9].…”

Host–Guest Polymer Complexes

“…Various host molecules such as cyclodextrins (CD), urea, thiourea, cyclo-triphosphazines, pillar [6]arene, cucurbit [6]uril, and calix [4]arene have been identified as undergoing inclusion complexation with a range of guest molecules. Among these host molecules, cyclodextrins are well-known for their complexation capabilities with a variety of guest molecules.…”

“…By complexation, the third and fourth articles in this Special Issue address these two major challenges in tissue regeneration [4,5]. By encapsulating oxygen into the cavities of α-CD and α-CD polymers, in vitro cell studies demonstrated a marked reduction in hypoxia-reoxygenation injury, leading to favorable cell growth and lowered cell mortality [4].…”

“…By complexation, the third and fourth articles in this Special Issue address these two major challenges in tissue regeneration [4,5]. By encapsulating oxygen into the cavities of α-CD and α-CD polymers, in vitro cell studies demonstrated a marked reduction in hypoxia-reoxygenation injury, leading to favorable cell growth and lowered cell mortality [4]. Similar to the approach reported by the first two studies [2,3], the fourth study reported the fabrication of a polyrotaxane (PR) containing α-CD and poly [ethylene glycol] containing silver sulfadiazine.…”