Review of Current Strategies for Delivering Alzheimer's Disease Drugs across the Blood-Brain Barrier

Int J Mol Sci. 2019 Jan 17;20(2):381. doi: 10.3390/ijms20020381.


Effective therapy for Alzheimer's disease is a major challenge in the pharmaceutical sciences. There are six FDA approved drugs (e.g., donepezil, memantine) that show some effectiveness; however, they only relieve symptoms. Two factors hamper research. First, the cause of Alzheimer's disease is not fully understood. Second, the blood-brain barrier restricts drug efficacy. This review summarized current knowledge relevant to both of these factors. First, we reviewed the pathophysiology of Alzheimer's disease. Next, we reviewed the structural and biological properties of the blood-brain barrier. We then described the most promising drug delivery systems that have been developed in recent years; these include polymeric nanoparticles, liposomes, metallic nanoparticles and cyclodextrins. Overall, we aim to provide ideas and clues to design effective drug delivery systems for penetrating the blood-brain barrier to treat Alzheimer's disease.

Keywords: Alzheimer’s disease; blood-brain barrier; brain delivery; cell-penetrating peptide; central nervous system; nanomaterials.

Publication types

  • Review

MeSH terms

  • Alzheimer Disease / drug therapy
  • Alzheimer Disease / etiology
  • Alzheimer Disease / metabolism*
  • Alzheimer Disease / pathology
  • Animals
  • Biomarkers
  • Blood-Brain Barrier / drug effects*
  • Blood-Brain Barrier / metabolism*
  • Drug Carriers / chemistry
  • Drug Delivery Systems* / methods
  • Humans
  • Nanoparticles / chemistry
  • Permeability
  • Theranostic Nanomedicine
  • Transcytosis


  • Biomarkers
  • Drug Carriers