In vivo evaluation of urokinase-loaded hollow nanogels for sonothrombolysis on suture embolization-induced acute ischemic stroke rat model
| Autor: | Xiaozhong Qu, Zhenzhong Yang, Haiqiang Jin, Yuanyuan Liu, Wei Cui, Yongan Sun, Hongjun Hao, Yining Huang, Yuming Teng, Mengnan Li, Ding Nan, Pu Lv, Chenghe Fan |
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| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
medicine.medical_treatment
Ultrasound responsive 030204 cardiovascular system & hematology ELIP echogenic liposomes 0302 clinical medicine Suture (anatomy) Embolization In vivo evaluation lcsh:QH301-705.5 nUK+US ultrasound and uPA-loaded nanogels Hollow nanogel US ultrasound HT hemorrhagic transformation TTC 2 3 5-triphenyltetrazolium chloride Thrombolysis EB evens blue Controlled release CCA common carotid artery Anesthesia Middle cerebral artery Urokinase delivery Biotechnology medicine.drug medicine.medical_specialty BBB blood-brain barrier Biomedical Engineering Urology UK+US ultrasound and free urokinase Article Biomaterials 03 medical and health sciences In vivo medicine.artery medicine lcsh:TA401-492 UK urokinase MCAO middle cerebral artery occlusion Urokinase TCD Transcranial Doppler business.industry SD Sprague-Dawley nUK uPA-loaded nanogels lcsh:Biology (General) lcsh:Materials of engineering and construction. Mechanics of materials MCA middle cerebral artery business Plasminogen activator MRI magnetic resonance imaging 030217 neurology & neurosurgery Hb hemoglobin |
| Zdroj: | Bioactive Materials, Vol 3, Iss 1, Pp 102-109 (2018) Bioactive Materials |
| Popis: | The urokinase-type plasminogen activator (uPA) loaded hollow nanogels (nUK) were synthesized by a one-step reaction of glycol chitosan and aldehyde capped poly (ethylene oxide). The resultant formulation is sensitive to diagnostic ultrasound (US) of 2 MHz. Herein, we evaluated the in vivo sonothrombolysis performance of the nUK on acute ischemic stroke rat model which was established by suture embolization of middle cerebral artery (MCA). Via intravenous (i.v.) administration, the experimental data prove a controlled release of the therapeutic protein around the clots under ultrasound stimulation, leading to enhanced thrombolysis efficiency of the nUK, evidenced from smaller infarct volume and better clinical scores when compared to the i.v. dose of free uPA no matter with or without US intervention. Meanwhile, the preservation ability of the nanogels not only prolonged the circulation duration of the protein, but also resulted in the better blood-brain barrier protection of the nUK formulation, showing no increased risk on the hemorrhagic transformation than the controls. This work suggests that the nUK is a safe sonothrombolytic formulation for the treatment of acute ischemic stroke. Graphical abstract Image 1 Highlights • Ultrasonic responsive urokinase (uPA)-loaded hollow nanogels (nUK) were synthesized for stroke treatment. • Acute ischemic stroke rat model was established by suture embolization of middle cerebral artery. • The nUK enhanced the sonothrombolytic efficacy and led to better BBB protection compared to the free uPA. |
| Databáze: | OpenAIRE |
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