ArticleJournal of controlled release : official journal of the Controlled Release Society2023
Targeted drug delivery to the brain endothelium dominates over passive delivery via vascular leak in experimental intracerebral hemorrhage.
Article in Journal of controlled release : official journal of the Controlled Release Society, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
What it found
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Who cites it
19 citing papers in PubMed, 33 citations in OpenAlex.
- Mitochondrial Protection and Neural Repair via ROS-Responsive Biomimetic Nanoparticles in Intracerebral Hemorrhage.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- ICAM-1 targeting of nanocarriers in a human blood-brain-barrier-on-a-chip complementsJournal of drug targeting · 2026Article
- Targeting DNA-LNPs to Endothelial Cells Improves Expression Magnitude, Duration, and Specificity.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Prehospital intensive blood pressure management in intracerebral hemorrhage: current evidence, controversies, and future directions.Frontiers in medicine · 2026Review
- Identification and Experimental Validation of Key Lipid Metabolism-Related Genes in Intracerebral Hemorrhage Based on Machine Learning.Journal of inflammation research · 2026Article
- Targeted lipid nanoparticles containing IL-10 mRNA improve outcomes in experimental intracerebral hemorrhage.Journal of neuroinflammation · 2025Article
- Multiple Applications of Nanomaterials in the Diagnosis and Treatment of Hemorrhagic Stroke.Biomolecules · 2025Review
- In Situ Proliferating Peptide Nanoparticle Augments Multi-Target Intervention of Secondary Brain Damage Following Subarachnoid Hemorrhage.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Endoscopic nasal delivery of engineered endothelial progenitor cell-derived exosomes improves angiogenesis and neurological deficits in rats with intracerebral hemorrhage.Materials today. Bio · 2025Article
- Transforming stroke treatment through nanotherapies.Nanomedicine (London, England) · 2025Article
- Tungsten-based polyoxometalate nanoclusters as ferroptosis inhibitors modulating S100A8/A9-mediated iron metabolism pathway for managing intracerebral haemorrhage.Journal of nanobiotechnology · 2025Article
- Multi-therapeutic-activity selenium nanodot toward preventing brain injury and restoring neurobehavioral functions following hemorrhagic stroke.Journal of nanobiotechnology · 2024Article
- Polymeric nanocarriers delivery systems in ischemic stroke for targeted therapeutic strategies.Journal of nanobiotechnology · 2024Review
- Combination of Physicochemical Tropism and Affinity Moiety Targeting of Lipid Nanoparticles Enhances Organ Targeting.Nano letters · 2024Article
- Nanoparticle-mediated delivery of non-viral gene editing technology to the brain.Progress in neurobiology · 2024Review
- Multiscale physics-basedFrontiers in drug delivery · 2024Review
- ATP5J regulates microglial activation via mitochondrial dysfunction, exacerbating neuroinflammation in intracerebral hemorrhage.Frontiers in immunology · 2024Article
- Article
- Targeted Nanocarriers Co-Opting Pulmonary Intravascular Leukocytes for Drug Delivery to the Injured Brain.ACS nano · 2023Article
Corrections and comments
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Authors and funding
13 authors at 4 institutions in 1 country.
Funding
Abstract
Intracerebral hemorrhage (ICH) is one of the most common causes of fatal stroke, yet has no specific drug therapies. Many attempts at passive intravenous (IV) delivery in ICH have failed to deliver drugs to the salvageable area around the hemorrhage. The passive delivery method assumes vascular leak through the ruptured blood-brain barrier will allow drug accumulation in the brain. Here we tested this assumption using intrastriatal injection of collagenase, a well-established experimental model of ICH. Fitting with hematoma expansion in clinical ICH, we showed that collagenase-induced blood leak drops significantly by 4 h after ICH onset and is gone by 24 h. We observed passive-leak brain accumulation also declines rapidly over ∼4 h for 3 model IV therapeutics (non-targeted IgG; a protein therapeutic; PEGylated nanoparticles). We compared these passive leak results with targeted brain delivery by IV monoclonal antibodies (mAbs) that actively bind vascular endothelium (anti-VCAM, anti-PECAM, anti-ICAM). Even at early time points after ICH induction, where there is high vascular leak, brain accumulation via passive leak is dwarfed by brain accumulation of endothelial-targeted agents: At 4 h after injury, anti-PECAM mAbs accumulate at 8-fold higher levels in the brain vs. non-immune IgG; anti-VCAM nanoparticles (NPs) deliver a protein therapeutic (superoxide dismutase, SOD) at 4.5-fold higher levels than the carrier-free therapeutic at 24 h after injury. These data suggest that relying on passive vascular leak provides inefficient delivery of therapeutics even at early time points after ICH, and that a better strategy might be targeted delivery to the brain endothelium, which serves as the gateway for the immune attack on the peri-hemorrhage inflamed brain region.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.