Single intranasal administration of 17β-estradiol loaded gelatin nanoparticles confers neuroprotection in the post-ischemic brain

Elizabeth Joachim; Radwa Barakat; Benjamin Lew; Kyekyoon Kevin Kim; CheMyong Ko; Hyungsoo Choi

doi:10.1016/j.nano.2020.102246

Single intranasal administration of 17β-estradiol loaded gelatin nanoparticles confers neuroprotection in the post-ischemic brain

Nanomedicine. 2020 Oct:29:102246. doi: 10.1016/j.nano.2020.102246. Epub 2020 Jun 24.

Authors

Elizabeth Joachim¹, Radwa Barakat², Benjamin Lew³, Kyekyoon Kevin Kim⁴, CheMyong Ko⁵, Hyungsoo Choi⁶

Affiliations

¹ Department of Bioengineering, University of Illinois at Urbana-Champaign, Urbana, IL, USA.
² Department of Comparative Biosciences, College of Veterinary Medicine, University of Illinois at Urbana-Champaign, Urbana, IL, USA; Department of Toxicology and Forensic Medicine, Faculty of Veterinary Medicine, Benha University, Qalyubia, Egypt.
³ Department of Electrical and Computer Engineering, University of Illinois at Urbana-Champaign, Urbana, IL, USA.
⁴ Department of Bioengineering, University of Illinois at Urbana-Champaign, Urbana, IL, USA; Department of Electrical and Computer Engineering, University of Illinois at Urbana-Champaign, Urbana, IL, USA. Electronic address: kevinkim@ilinois.edu.
⁵ Department of Comparative Biosciences, College of Veterinary Medicine, University of Illinois at Urbana-Champaign, Urbana, IL, USA. Electronic address: jayko@illinois.edu.
⁶ Department of Electrical and Computer Engineering, University of Illinois at Urbana-Champaign, Urbana, IL, USA. Electronic address: hyungsoo@illinois.edu.

PMID: 32590106
DOI: 10.1016/j.nano.2020.102246

Abstract

Globally, ischemic stroke is a leading cause of death and adult disability. Previous efforts to repair damaged brain tissue following ischemic events have been hindered by the relative isolation of the central nervous system. We have developed a gelatin nanoparticle-mediated intranasal drug delivery system as an efficient, non-invasive method for delivering 17β-estradiol (E2) specifically to the brain, enhancing neuroprotection, and limiting systemic side effects. Young adult male C57BL/6 J mice subjected to 30 min of middle cerebral artery occlusion (MCAO) were administered intranasal preparations of E2-GNPs, water soluble E2, or saline as control 1 h after reperfusion. Following intranasal administration of 500 ng E2-GNPs, brain E2 content rose by 5.24 fold (P<0.0001) after 30 min and remained elevated by 2.5 fold at 2 h (P<0.05). The 100 ng dose of E2-GNPs reduced mean infarct volume by 54.3% (P<0.05, n=4) in comparison to saline treated controls, demonstrating our intranasal delivery system's efficacy.

Keywords: Estrogen; Gelatin nanoparticles; Intranasal delivery; MCAO.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Administration, Intranasal
Animals
Brain / drug effects
Brain / pathology
Brain Ischemia / drug therapy*
Brain Ischemia / pathology
Disease Models, Animal
Estradiol / chemistry
Estradiol / pharmacology*
Gelatin / chemistry
Gelatin / pharmacology
Humans
Infarction, Middle Cerebral Artery / drug therapy*
Infarction, Middle Cerebral Artery / pathology
Mice
Nanoparticles / chemistry*
Neuroprotection / drug effects

Substances

Estradiol
Gelatin