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Engineering triiodothyronine (T3) nanoparticle for use in ischemic brain stroke
Alexander Mdzinarishvili1, Vijaykumar Sutariya, Phani K Talasila
1Department of Pharmaceutical Sciences, College of Pharmacy, Northeast Ohio Medical University, 4209 State Route 44, Rootstown, OH 44272 USA.
Drug Delivery and Translational Research
|July 19, 2013
Summary
Thyroid hormone (T3) delivered via nanoparticles significantly improves treatment for ischemic stroke. This neuroprotective strategy reduced brain infarction and edema more effectively than T3 solution alone.
Area of Science:
- Neuroscience
- Pharmacology
- Biomaterials Science
Background:
- Ischemic stroke requires rapid neuroprotection.
- Thyroid hormone (T3) shows promise but needs enhanced delivery.
- Nanoparticulate systems offer potential for targeted drug delivery across the blood-brain barrier.
Purpose of the Study:
- To investigate if encapsulating T3 in poly-(lactide-co-glycolide)-polyethyleneglycol (PLGA-b-PEG) nanoparticles enhances its neuroprotective efficacy in ischemic stroke.
- To evaluate the impact of glutathione coating on nanoparticle brain targeting and therapeutic benefit.
Main Methods:
- PLGA-b-PEG nanoparticles encapsulating T3 were formulated, with some coated with glutathione.
- Nanoparticle characteristics (size, zeta potential) were analyzed.
- Cellular uptake and reporter gene expression were assessed.
- Efficacy was evaluated in a middle cerebral artery occlusion (MCAO) model of ischemic stroke, measuring tissue infarction and brain edema.
Main Results:
- T3-loaded nanoparticles were successfully generated in the nano range.
- Both coated and uncoated nanoparticles were internalized by cells, activating thyroid hormone response elements.
- T3 nanoparticles significantly reduced tissue infarction and brain edema compared to T3 solution in the MCAO model.
- Glutathione-coated nanoparticles showed slightly improved, though comparable, efficacy to uncoated nanoparticles.
Conclusions:
- Nanoparticulate delivery of T3 represents a superior strategy for managing ischemic stroke compared to traditional T3 solutions.
- Glutathione coating may further enhance brain-targeted delivery, optimizing neuroprotection.
- This approach holds significant potential for improving therapeutic outcomes in ischemic stroke patients.
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