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Intranasal 17β-Estradiol Modulates Spatial Learning and Memory in a Rat Model of Surgical Menopause.

Alesia V Prakapenka1,2,3, Veronica L Peña1,3, Isabel Strouse1,3

  • 1Department of Psychology, Arizona State University, Tempe, AZ 85281, USA.

Pharmaceutics
|December 22, 2020
PubMed
Summary

Intranasal 17β-estradiol (E2) improved memory, but cyclodextrin-solubilized E2 impaired working memory and increased uterine stimulation. Free E2 offers a better brain delivery strategy with fewer peripheral effects.

Keywords:
cyclodextrindeliveryestrogenintranasallearningmemorymenopause

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Area of Science:

  • Neuroscience
  • Pharmacology
  • Endocrinology

Background:

  • 17β-estradiol (E2) administration can enhance cognitive function but causes peripheral side effects.
  • Intranasal drug delivery is a promising route for brain-specific targeting.
  • Cyclodextrins can modify drug distribution in the brain, influencing therapeutic outcomes.

Purpose of the Study:

  • To investigate how different cyclodextrin formulations affect the brain distribution of intranasally administered E2.
  • To compare the cognitive and peripheral effects of freely administered E2 versus cyclodextrin-solubilized E2 in ovariectomized rats.

Main Methods:

  • Tritiated E2 distribution was measured in brain regions and peripheral organs after intranasal administration of free E2 or E2 complexed with different cyclodextrins.
  • Cognitive performance (spatial learning and memory) and uterine horn weights were assessed.

Main Results:

  • Free intranasal E2 improved spatial reference memory, while cyclodextrin-E2 impaired spatial working memory.
  • Both E2 formulations increased uterine horn weights, with cyclodextrin-E2 showing a more pronounced effect.
  • Specific cyclodextrin formulations altered E2 brain distribution, impacting cognitive and peripheral outcomes.

Conclusions:

  • Freely solubilized intranasal E2 enhances cognitive benefits with reduced peripheral stimulation compared to cyclodextrin-solubilized E2.
  • Intranasal administration of free E2 represents a strategic approach for targeted brain delivery.
  • Cyclodextrin complexation can alter E2's efficacy and safety profile, necessitating careful formulation selection.