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

Authors

  • Hiteshkumar Patel Department of Pharmaceutics, Sankalchand Patel University, Visnagar, Gujarat, India
  • Jayvadan Patel Formulation Scientist, Aavis Pharmaceuticals, Hoschton, Georgia, USA
  • Anita Patel Research Associate, Samrajya Aromatics Pvt. Ltd., Gandhinagar, Gujarat, India

DOI:

https://doi.org/10.55940/medphar202463

Keywords:

Anti-edema activity, blood–brain barrier, brain targeted nanoparticles, ischemic brain stroke, supercritical fluid technique, thyroid hormone

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.

ResultsThe 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.

References

Banerjee TK, Das SK. Fifty years of stroke researches in India. Ann Indian Acad Neurol. 2016;19(1):1-8. DOI: 10.4103/0972-2327.168631

Raslan A, Bhardwaj A. Medical management of cerebral edema. Neurosurg. Focus. 2007;22(5):1-2. DOI: 10.3171/foc.2007.22.5.13

Green AR. Pharmacological approaches to acute ischaemic stroke: reperfusion certainly, neuroprotection possibly. Br. J. Pharmacol. 2008;153(S1):S325-38. DOI: 10.1038/sj.bjp.0707594

Suzuki S, Brown CM, Wise PM. Neuroprotective effects of estrogens following ischemic stroke. Front Endocrinol. 2009 ;30(2):201-11. DOI: 10.1016/j.yfrne.2009.04.007

Sayeed I, Stein DG. Progesterone as a neuroprotective factor in traumatic and ischemic brain injury. Prog Brain Res. 2009 ;175:219-37. DOI: 10.1016/S0079-6123(09)17515-5

Ma Y, Zhou Z, Yang GY, Ding J, Wang X. The effect of erythropoietin and its derivatives on ischemic stroke therapy: a comprehensive review. Front. pharmacol. 2022;13:743926. DOI: 10.3389/fphar.2022.743926

Puzio M, Moreton N, O'Connor JJ. Neuroprotective strategies for acute ischemic stroke: targeting oxidative stress and prolyl hydroxylase domain inhibition in synaptic signalling. Brain Disorders. 2022;5:100030. DOI: 10.1016/j.dscb.2022.100030

Reddy MK, Labhasetwar V. Nanoparticle‐mediated delivery of superoxide dismutase to the brain: an effective strategy to reduce ischemia‐reperfusion injury. The FASEB Journal. 2009;23(5):1384-95. DOI: 10.1096/fj.08-116947

Yoshimura S, Sakai N, Yamagami H, Uchida K, Beppu M, Toyoda K, Matsumaru Y, Matsumoto Y, Kimura K, Takeuchi M, Yazawa Y. Endovascular therapy for acute stroke with a large ischemic region. N Engl J Med. 2022;386(14):1303-13. DOI: 10.1056/NEJMoa2118191

Kimelberg HK. Water homeostasis in the brain: basic concepts. Neurosci. 2004 ;129(4):851-60. DOI:10.1016/j.neuroscience.2004.07.033

Wan Y, Holste KG, Hua Y, Keep RF, Xi G. Brain edema formation and therapy after intracerebral hemorrhage. Neurobiol. Dis. 2023;176:105948. DOI: 10.1016/j.nbd.2022.105948

Sible IJ, Yew B, Dutt S, Li Y, Blanken AE, Jang JY, Ho JK, Marshall AJ, Kapoor A, Gaubert A, Bangen KJ. Selective vulnerability of medial temporal regions to short-term blood pressure variability and cerebral hypoperfusion in older adults. Neuroimage Rep. 2022 ;2(1):100080. DOI:10.1016/j.ynirp.2022.100080

Belov Kirdajova D, Kriska J, Tureckova J, Anderova M. Ischemia-triggered glutamate excitotoxicity from the perspective of glial cells. Front. cell. neurosci. 2020;14:51.

DOI:10.3389/fncel.2020.00051

Seifert G, Schilling K, Steinhäuser C. Astrocyte dysfunction in neurological disorders: a molecular perspective. Nat. Rev. Neurosci. 2006;7(3):194-206. DOI: 10.1038/nrn1870

Rothman SM, Olney JW. Excitotoxicity and the NMDA receptor--still lethal after eight years. Trends Neurosci. 1995;18(2):57-8. DOI: 10.1016/0166-2236(95)93869-y

Zhang Y, Zhang G, Chen X. Elevated Calcium after Acute Ischemic Stroke Predicts Severity and Prognosis. Mol. Neurobiol. 2024; 61(1):266-75. DOI:10.1007/s12035-023-03581-8

Arundine M, Tymianski M. Molecular mechanisms of glutamate-dependent neurodegeneration in ischemia and traumatic brain injury. Cell Mol Life Sci. 2004;61:657-68. DOI: 10.1007/s00018-003-3319-x

Al_hussaniy HA, Alkhafaje Z, Altamimi ZS, Oraibi AI, Abdalhassan AH, Abdulhamza HM, AL-Zobaidy MJ. Memantine and its role in parkinsonism, seizure, depression, migraine headache, and Alzheimer’s disease. Pharmacia. 2023 5;70(2):291-7. DOI:10.3897/pharmacia.70.e99311

Lipton P. Ischemic cell death in brain neurons. Physiol. Rev. 1999;79(4):1431-568. DOI: 10.1152/physrev.1999.79.4.1431

Christophe B, Karatela M, Sanchez J, Pucci J, Connolly ES. Statin therapy in ischemic stroke models: a meta-analysis. Transl. Stroke Res. 2020;11:590-600.

DOI: 10.1007/s12975-019-00750-7

Geldenhuys W, Mbimba T, Bui T, Harrison K, Sutariya V. Brain-targeted delivery of paclitaxel using glutathione-coated nanoparticles for brain cancers. J DRUG TARGET. 2011;19(9):837-45. DOI: 10.3109/1061186X.2011.589435

Ahmad S, Khan I, Pandit J, Emad NA, Bano S, Dar KI, Rizvi MM, Ansari MD, Aqil M, Sultana Y. Brain targeted delivery of carmustine using chitosan coated nanoparticles via nasal route for glioblastoma treatment. Int. J. Biol. Macromol. 2022;221:435-45. DOI: 10.1016/j.ijbiomac.2022.08.210

Ishii T, Fukuta T, Agato Y, Oyama D, Yasuda N, Shimizu K, Kawaguchi AT, Asai T, Oku N. Nanoparticles accumulate in ischemic core and penumbra region even when cerebral perfusion is reduced. Biochem Biophys Res Commun. 2013 ;430(4):1201-5. DOI: 10.1016/j.bbrc.2012.12.080

Kreuter J. Nanoparticles—a historical perspective. Int J Pharm. 2007;331(1):1-0. DOI: 10.1016/j.ijpharm.2006.10.021

Tosi G, Costantino L, Ruozi B, Forni F, Vandelli MA. Polymeric nanoparticles for the drug delivery to the central nervous system. Expert Opin Drug Deliv. 2008;5(2):155-74. DOI:10.1517/17425247.5.2.155

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Published

2024-04-15

How to Cite

Patel, H., Patel , J., & Patel , A. (2024). Enhancement of neuroprotective and anti-edema action in mice ischemic stroke model using T3 loaded nanoparticles. Medical and Pharmaceutical Journal, 3(1), 1–12. https://doi.org/10.55940/medphar202463

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