Hypoxia modeling techniques: A review

Salyha, N. O.; Oliynyk, Iryna

doi:10.1016/j.heliyon.2023.e13238

Cited by 6 publications

(4 citation statements)

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“…This Account highlights recent progress of azocalixarene-based HGDDSs, and some key experiences were gained from it: (1) Azocalixarene is easy to synthesize and has precise molecular weight and well-defined molecular structure, simplifying quality control. (2) The longitudinal expansion of the calixarene cavity effectively enhances the binding affinities.…”

Section: Discussionmentioning

confidence: 99%

“…Hypoxia is a salient feature of numerous diseases such as tumors, rheumatoid arthritis (RA), bacterial infections, kidney injury, stroke, and myocardial infarction . It may cause by inadequate blood supply, respiratory dysfunction, tissue damage or pathology, and metabolic abnormalities . Taking a solid tumor as an example, the oxygen concentration can decrease to 0.02–2% (2–9% in normal tissue) .…”

Section: Introductionmentioning

confidence: 99%

“…1 It may cause by inadequate blood supply, respiratory dysfunction, tissue damage or pathology, and metabolic abnormalities. 2 Taking a solid tumor as an example, the oxygen concentration can decrease to 0.02−2% (2−9% in normal tissue). 3 This decrease is because, in intensively proliferating and expanding tumor tissue, the oxygen demand surpasses oxygen supply, and the distance between cells and the existing vasculature increases, hampering oxygen diffusion.…”

Section: Introductionmentioning

confidence: 99%

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Hypoxia-Responsive Host–Guest Drug Delivery System

Hu,

Fu,

Guo

2023

Acc. Mater. Res.

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Conspectus A host–guest drug delivery system (HGDDS) refers to a host–guest complex of an artificial receptor and a therapeutic agent which can dissociate at the lesion site and release the loaded cargo. Macrocyclic receptors are promising drug carriers because of their superior properties, including ease of preparation, precise molecular weight, well-defined molecular structure, and excellent chemical stability. The host–guest loading process is mild, simple, and repeatable. The host–guest formulations can quantitatively load drug because of the exact cavity-loading pattern and quantifiable host–guest binding constant. Host–guest formulations are typically modular, which may be appealing in the context of personalized medicine because the macrocyclic carriers can act as a platform to complex diverse drugs. These lead to good batch reproductivity and excellent application prospects in both scientific research and industry. However, in order to make the HGDDS more suitable for practical application, several demands such as high binding affinity, universal binding to multiple drugs, targeting, and stimuli-responsiveness still need to be considered. The process of hypoxia is linked to several diseases and biological processes, including cancer, acute and chronic diseases, pathogenic microbe infection, and other stress responses. As part of our ongoing research on supramolecular biomaterials based on macrocycles by taking advantage of their recognition and assembly properties, we have developed a hypoxia-responsive HGDDS based on azocalixarenes. These azocalixarenes possess a deepened cavity, resulting in high binding affinities and high encapsulation efficiencies toward therapeutic agents. The azo group is one of the most frequently employed hypoxia-responsive moieties as it can be reduced under hypoxic microenvironments. This property confers the carriers with hypoxia-triggered release due to the remarkable decrease in binding affinities following reduction. The fast release kinetics further facilitates the efficient accumulation of drugs at the lesion site. These azocalixarene-based HGDDSs have been applied in preclinical studies for diagnosis and treatment of several diseases including tumor, bacterial infection, kidney injury, and rheumatoid arthritis. In this Account, we outline our recent efforts in designing and formulating HGDDSs based on azocalixarenes. We first provide a brief introduction of HGDDSs, including their features, the quantitative loading and ratiometric delivery models. Then the molecular design principles and synthesis methods, the strong binding affinity, the drug loading, and the fast hypoxia-response of azocalixarene-based HGDDSs are described. The applications of azocalixarene-based HGDDSs in treating different diseases are followed. Finally, despite the rapid development of azocalixarene-based HGDDSs, there are still several problems that need to be solved both scientifically and in terms of clinical translation. Therefore, we propose perspectives that can be further conducted on HGDDSs.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Hypoxia-Responsive Host–Guest Drug Delivery System

Hu,

Fu,

Guo

2023

Acc. Mater. Res.

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“…In literature available hypoxia rat models were recently systematized in a review article (Salyha and Oliynyk, 2023). The authors present a differentiation in exogenous hypoxia models, including hypobaric (decreased oxygen partial pressure accompanied by a changed barometric air pressure) or normobaric (percentage drop in oxygen in the inhaled air at a barometric pressure of 750 mmHg caused by an altered gas composition) methods, and endogenous hypoxia models, which mimic the pathophysiology of the investigated diseases.…”

Section: Introductionmentioning

confidence: 99%

Innovative in vivo rat model for global cerebral hypoxia: a new approach to investigate therapeutic and preventive drugs

Stahlke,

Frai,

Busse

et al. 2024

Front. Physiol.

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Introduction: Severe acute global cerebral hypoxia can lead to significant disability in humans. Although different animal models have been described to study hypoxia, there is no endogenous model that considers hypoxia and its effect on the brain as an independent factor. Thus, we developed a minimally invasive rat model, which is based on the non-depolarizing muscle blocking agent rocuronium in anesthetized animals. This drug causes respiratory insufficiency by paralysis of the striated muscles.Methods: In this study, 14 rats underwent 12 min of hypoxemia with an oxygen saturation of approximately 60% measured by pulse oximetry; thereafter, animals obtained sugammadex to antagonize rocuronium immediately.Results: Compared to controls (14 rats, anesthesia only), hypoxic animals demonstrated significant morphological alterations in the hippocampus (cell decrease in the CA 1 region) and the cerebellum (Purkinje cell decrease), as well as significant changes in hypoxia markers in blood (Hif2α, Il1β, Tgf1β, Tnfα, S100b, cspg2, neuron-specific enolase), hippocampus (Il1β, Tnfα, S100b, cspg2, NSE), and cerebellum (Hif1α, Tnfα, S100b, cspg2, NSE). Effects were more pronounced in females than in males.Discussion: Consequently, this model is suitable to induce hypoxemia with consecutive global cerebral hypoxia. As significant morphological and biochemical changes were proven, it can be used to investigate therapeutic and preventive drugs for global cerebral hypoxia.

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