Brain-Targeted Delivery of Estradiol

Abstract

Estradiol is the most potent human estrogen, and because many of its pharmacologic effects are mediated through the central nervous system (CNS), there are several potential therapeutic applications for a system that could achieve brain-targeted delivery. By directing the active compound away from the circulatory system and behind the blood-brain barrier, brain-targeting should increase treatment efficiency for CNS-mediated effects and reduce the likelihood of peripheral adverse effects, such as increased risks for cancer (the main reason many women avoid traditional hormone therapy). Possible therapeutic applications include the treatment of menopausal vasomotor symptoms (hot flashes), the treatment and/or prevention of various types of dementia (including Alzheimer disease), treatment of male or female sexual dysfunction, and possibly neuroprotection. Preclinical and clinical results obtained with an estradiol chemical delivery system, an innovative chemical entity that uses a redox CDS approach to selectively target estradiol to the brain and CNS by releasing it following a designed metabolic sequence, demonstrate effective brain-targeting and long-lasting pharmacologic activity, thus confirming the potential of this approach.