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Dose–Response Relationship and Threshold Drug Dosage Identification for a Novel Hybrid Mechanical-Thrombolytic System with an Ultra-Low Dose Patch

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Abstract

Introduction

Ischemic stroke treatment has advanced in the last two decades and intravenous thrombolysis is now considered the standard of care for selected patients. Recanalization can also be achieved by mechanical endovascular treatment for patients with large vessel occlusions. Complicating treatment-related symptomatic intracerebral hemorrhage and prolonged needle-to-recanalization times have been identified as major determinants of poor three-month functional outcomes. A hybrid mechanical-thrombolytic system with a patch imbued with an ultra-low dose of thrombolytic agents loaded onto a stent-retriever has been developed.

Methods

In this study, the in situ dose–response relationship of the thrombolytic patch imbued with up to 1000 IU of urokinase plasminogen activator (uPA) was quantified using Raman spectroscopy.

Results

Thrombi of up to 400 μm thickness dissolved within 15 min when patches imbued with < 1% of the conventional thrombolysis therapy dosage were applied. The results demonstrated that low-dose thrombolytic patches can dissolve normal clots compressed in the blood vessel in a short time. 500 IU is the threshold uPA dosage in the thrombolytic patch that most effectively dissolves the clots.

Conclusion

This study suggests that a novel endovascular stent-retriever loaded with an ultra-low drug dose fibrinolytic patch may be a suitable treatment for patients who are ineligible for conventional thrombolytic therapy.

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Acknowledgments

We would like to thank the Kwong Wah Hospital for providing clinical support, and the Materials Characterization and Preparation Facility (MCPF) for providing technical support. This research was supported in part by a donation from Mr. Louis NG [Grant Number: PD-NHK17EG01].

Conflict of interest

There is a filed US provisional patent application (US 62172044) in this paper related to Zhen Qin, Chi Hang Chon, John Ching Kwong Kwok, and David C C Lam. Peter Yat Ming Woo declares that he has no conflicts of interest.

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No human studies or animal studies were carried out by the authors for this article.

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Authors and Affiliations

  1. Department of Mechanical and Aerospace Engineering, The Hong Kong University of Science and Technology, Kowloon, Hong Kong

    Zhen Qin, Chi Hang Chon, John Ching Kwong Kwok & David C. C. Lam

  2. Department of Neurosurgery, Kwong Wah Hospital, Hong Kong, Hong Kong

    John Ching Kwong Kwok & Peter Yat Ming Woo

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  1. Zhen Qin
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Qin, Z., Chon, C.H., Kwok, J.C.K. et al. Dose–Response Relationship and Threshold Drug Dosage Identification for a Novel Hybrid Mechanical-Thrombolytic System with an Ultra-Low Dose Patch. Cel. Mol. Bioeng. 14, 627–637 (2021). https://doi.org/10.1007/s12195-021-00683-y

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