pH gradient difference around ischemic brain tissue can serve as a trigger for delivering polyethylene glycol-conjugated urokinase nanogels

Journal of Controlled Release : Official Journal of the Controlled Release Society
Wei CuiYining Huang

Abstract

pH-sensitive polyethylene glycol-conjugated urokinase nanogels (PEG-UKs) were previously reported to be a new form of UK nanogels that could release UK at certain pH values. In this study, we evaluated the effect of PEG-UK targeted to ischemic tissue with microcirculation failure in rat model of ischemic stroke and investigated the possible mechanisms of action. Surgeries were performed to induce persistent middle cerebral artery (MCA) occlusion in adult Sprague-Dawley rats. The pH distribution in the brain was mapped 1h after ischemia using a needle-type pH micro sensor. The release curve of active UK from PEG-UK was also mapped by a continuous measurement of the peripheral blood. The thrombolytic effects of PEG-UK, when it was administrated 1h after occlusion, including dynamic changes in the D-dimer level, neurological deficits and infarction volume, were observed. Next, the possible mechanisms underlying these effects were explored, including the BBB integrity and the extent of apoptosis and neurotoxicity. Additionally, the long-term effects of PEG-UK during the four weeks after treatment were evaluated using the dynamic changes in the body weights and clinical scores and the numbers of deaths and hemorrhagic transformation...Continue Reading

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Citations

Jul 14, 2016·Chemistry, an Asian Journal·Xiaozhong Qu, Zhenzhong Yang
Dec 28, 2017·Journal of Materials Chemistry. B, Materials for Biology and Medicine·Hamed AmaniOmid Akhavan
Oct 27, 2020·Nanomedicine·Filippo PinelliFilippo Rossi
Jan 25, 2020·Drug Discovery Today·Saeideh NozohouriThomas J Abbruscato
Jun 3, 2021·Life·Sara Bernardo-CastroJoão Sargento-Freitas

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