ArticleTranslational stroke research2021
Combination of Polyethylene Glycol-Conjugated Urokinase Nanogels and Urokinase for Acute Ischemic Stroke Therapeutic Implications.
Article in Translational stroke research, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 22 citations in OpenAlex.
- Polymer Network-Based Nanogels and Microgels: Design, Classification, Synthesis, and Applications in Drug Delivery.Gels (Basel, Switzerland) · 2025Review
- Revolutionizing Stroke Care: Nanotechnology-Based Brain Delivery as a Novel Paradigm for Treatment and Diagnosis.Molecular neurobiology · 2025Review
- Overview of Venous Thromboembolism and Emerging Therapeutic Technologies Based on Nanocarriers-Mediated Drug Delivery Systems.Molecules (Basel, Switzerland) · 2024Review
- The relationship between ischemic penumbra progression and the oxygen content of cortex microcirculation in acute ischemic stroke.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2024Article
- Polymeric nanocarriers delivery systems in ischemic stroke for targeted therapeutic strategies.Journal of nanobiotechnology · 2024Review
- Advances in Nano-Functional Materials in Targeted Thrombolytic Drug Delivery.Molecules (Basel, Switzerland) · 2024Review
- Progress of nanomaterials in the treatment of thrombus.Drug delivery and translational research · 2024Review
- Advanced Nano-Drug Delivery Systems in the Treatment of Ischemic Stroke.Molecules (Basel, Switzerland) · 2024Review
- Intra-Arterial Thrombolysis is Associated with Delayed Reperfusion of Remaining Vessel Occlusions following Incomplete Thrombectomy.AJNR. American journal of neuroradiology · 2023Article
- Poly-Molecules (Basel, Switzerland) · 2023Article
- Advances in the research of nano delivery systems in ischemic stroke.Frontiers in bioengineering and biotechnology · 2022Review
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Tissue reperfusion is a serious therapeutic strategy of ischemic stroke in addition to recanalization. In this work, we aimed to establish new urokinase-based therapeutics in order to dissolve large vessel thrombus together with microthrombi for stroke implications. Formulations consisted of free urokinase (UK), polyethylene glycol-crosslinked urokinase nanogel (PEG-UK), and a 1:1 mixture of UK and PEG-UK (PEG-UK+UK) were tested both in vitro and in vivo. In vitro experiments confirmed the pH-dependent release of PEG-UK in the PEG-UK+UK formulation. It was activated at pH 6.50, an environmental pH in the infarct brain tissue, owing to the dynamic crosslink property of PEG-UK. In vivo tests on a thromboembolic stroke rat model showed that the formulations containing UK, i.e., free UK and PEG-UK+UK, demonstrated better neurological scores and smaller infarction volumes within the time window, in which the PEG-UK+UK formulation relatively performed better. On the other hand, the formulations containing PEG-UK, i.e., PEG-UK and PEG-UK+UK, gained sufficient thrombolytic efficiency beyond the time window. Further investigation on the mechanism revealed that PEG-UK could reduce microthrombus in distal microcirculation, and its destructive effect was also less than that of free UK. The PEG-UK+UK formulation actually provided a "dual targeting" delivery of UK to both the large vessels and the microcirculation, which was beneficial to the treatment of cerebral ischemic stroke both within and beyond the therapeutic time window.
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Registered trials
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