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Updated: Jan 21, 2026

Optimized Management of Endovascular Treatment for Acute Ischemic Stroke
09:21

Optimized Management of Endovascular Treatment for Acute Ischemic Stroke

Published on: January 18, 2018

12.5K

Sequentially Site-Specific Delivery of Thrombolytics and Neuroprotectant for Enhanced Treatment of Ischemic Stroke

Jianpei Xu1,2, Xiaoqi Wang1,2, Haoyuan Yin1

  • 1Department of Pharmaceutics, School of Pharmacy , Nanjing Medical University , Nanjing 211166 , China.

ACS Nano
|July 25, 2019
PubMed

Ischemic stroke caused by a thrombus clog and ischemia is one of the most lethal and disabling cerebrovascular diseases. A sequentially targeted delivery system is highly desired to deliver thrombolytics and neuroprotectant to the site of the thrombus and ischemic penumbra, respectively, to pursue a maximized combinational effect. Inspired by the vital roles that platelets play in thrombus formation, herein, we develop a bioengineered "nanoplatelet" (tP-NP-rtPA/ZL006e) for sequentially site-specific delivery of recombinant tissue plasminogen activator (rtPA) and neuroprotectant (ZL006e) for ischemic stroke treatment. The tP-NP-rtPA/ZL006e consists of a ZL006e-loaded dextran derivative polymeric nanoparticle core and platelet membrane shell conjugated with thrombin-cleavable Tat-peptide-coupled rtPA. Mediated by the cloak of the platelet membrane, tP-NP-rtPA/ZL006e targets the thrombus site and rtPA is triggered to release by the upregulated thrombin. Subsequently, the in situ exposed Tat peptide enhanced penetration of the "nanoplatelet" across the blood-brain barrier into ischemic brain for ZL006e site-specific delivery. From the in vitro and in vivo evaluation, tP-NP-rtPA/ZL006e is demonstrated to significantly enhance the anti-ischemic stroke efficacy in the rat model  with middle cerebral artery occlusion, showing a 63 and 72% decrease in ischemic area and reactive oxygen species level compared to that with free drug combination, respectively.

Keywords:
bioresponsive materialsdrug deliveryischemic strokenanomedicineplatelet

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