Enhancement of neuroprotective and anti-edema action in mice ischemic stroke model using T3 loaded nanoparticles

Abstract

Background: cerebral ischemia still represents one of the most common causes of death and disability worldwide. A prompt treatment using strong neuroprotective medications is one potential method of pharmacological therapy for brain ischemic stroke patients. Thyroid hormone (T3) has been demonstrated to protect against ischemic damage. Despite the fact that thyroid hormone may pass across the blood-brain barrier (BBB). Objective: we hypothesized that the effectiveness of thyroid hormone in ischemic brain stroke can be improved by encapsulation in nanoparticulate delivery vehicles. Methods: We tested our hypothesis by generating thyroid hormone encapsulated in nanoparticles or brain-targeted nanoparticles using biodegradable polymers by utilizing an environment-friendly Supercritical Assisted Atomization (SAA) process as an alternative to a thyroid hormone solution in the setting of the MCAO stroke model. The biggest benefit of our proposed exploit of thyroid hormones in ischemic stroke is the fact that this strategy uses the body’s endogenous hormones at sub-toxic levels to afford significant improvement in a life-endangering situation. According to our preliminary studied considerations, some tests were performed setting the saturator operating conditions in a pressure range between 5 and 15MPa and a temperature range between 70 and 90oC. Results: The best results in terms of stability of the process and morphology of thyroid hormone nanoparticles were observed operating at 10MPa and 80oC. Our preliminary investigations also show that treatment with T3 significantly decreased infarct area (~36%) and analysis of hemispheric areas for edema formation showed that the edema formation induced by transient-MCAO was reduced by ~60% upon T3 treatment. Conclusion: Thus, innovation in our proposal lies in our hypothesis, and our novel approaches directed at tackling edema in stroke.