Menthol-Modified Quercetin Liposomes with Brain-Targeting Function for the Treatment of Senescent Alzheimer's Disease

ACS Chem Neurosci. 2024 Jun 5;15(11):2283-2295. doi: 10.1021/acschemneuro.4c00109. Epub 2024 May 23.

Abstract

Oxidative stress and neuroinflammation in the aging brain are correlated with the development of neurodegenerative diseases, such as Alzheimer's disease (AD). The blood-brain barrier (BBB) poses a significant challenge to the effective delivery of therapeutics for AD. Prior research has demonstrated that menthol (Men) can augment the permeability of the BBB. Consequently, in the current study, we modified Men on the surface of liposomes to construct menthol-modified quercetin liposomes (Men-Qu-Lips), designed to cross the BBB and enhance quercetin (Qu) concentration in the brain for improved therapeutic efficacy. The experimental findings indicate that Men-Qu-Lips exhibited good encapsulation efficiency and stability, successfully crossed the BBB, improved oxidative stress and neuroinflammation in the brains of aged mice, protected neurons, and enhanced their learning and memory abilities.

Keywords: Alzheimer’s disease; aging; blood–brain barrier; menthol; quercetin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aging / drug effects
  • Alzheimer Disease* / drug therapy
  • Alzheimer Disease* / metabolism
  • Animals
  • Blood-Brain Barrier* / drug effects
  • Blood-Brain Barrier* / metabolism
  • Brain* / drug effects
  • Brain* / metabolism
  • Liposomes*
  • Male
  • Menthol* / administration & dosage
  • Menthol* / pharmacology
  • Mice
  • Mice, Inbred C57BL
  • Oxidative Stress / drug effects
  • Quercetin* / administration & dosage
  • Quercetin* / chemistry
  • Quercetin* / pharmacology

Substances

  • Quercetin
  • Liposomes
  • Menthol