Current Strategies for Brain Drug Delivery

Theranostics. 2018 Feb 5;8(6):1481-1493. doi: 10.7150/thno.21254. eCollection 2018.


The blood-brain barrier (BBB) has been a great hurdle for brain drug delivery. The BBB in healthy brain is a diffusion barrier essential for protecting normal brain function by impeding most compounds from transiting from the blood to the brain; only small molecules can cross the BBB. Under certain pathological conditions of diseases such as stroke, diabetes, seizures, multiple sclerosis, Parkinson's disease and Alzheimer disease, the BBB is disrupted. The objective of this review is to provide a broad overview on current strategies for brain drug delivery and related subjects from the past five years. It is hoped that this review could inspire readers to discover possible approaches to deliver drugs into the brain. After an initial overview of the BBB structure and function in both healthy and pathological conditions, this review re-visits, according to recent publications, some questions that are controversial, such as whether nanoparticles by themselves could cross the BBB and whether drugs are specifically transferred to the brain by actively targeted nanoparticles. Current non-nanoparticle strategies are also reviewed, such as delivery of drugs through the permeable BBB under pathological conditions and using non-invasive techniques to enhance brain drug uptake. Finally, one particular area that is often neglected in brain drug delivery is the influence of aging on the BBB, which is captured in this review based on the limited studies in the literature.

Keywords: actively targeted delivery; aging; disease conditions; permeable blood-brain barrier.

Publication types

  • Review

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / metabolism
  • Animals
  • Biological Transport
  • Blood-Brain Barrier / drug effects
  • Blood-Brain Barrier / metabolism*
  • Brain / drug effects
  • Brain / metabolism*
  • Diabetes Mellitus / drug therapy
  • Diabetes Mellitus / metabolism
  • Diabetes Mellitus / pathology
  • Drug Carriers / chemistry
  • Drug Carriers / classification
  • Drug Carriers / pharmacokinetics*
  • Exosomes / metabolism
  • Genetic Vectors / metabolism
  • Genetic Vectors / pharmacokinetics
  • Glucose Transporter Type 1 / metabolism
  • Humans
  • Nanoparticles / administration & dosage
  • Nanoparticles / metabolism
  • Neurodegenerative Diseases / drug therapy
  • Neurodegenerative Diseases / metabolism
  • Neurodegenerative Diseases / pathology
  • Prescription Drugs / pharmacokinetics*
  • Prescription Drugs / pharmacology
  • Theranostic Nanomedicine / methods*
  • Viruses / metabolism


  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • Drug Carriers
  • Glucose Transporter Type 1
  • Prescription Drugs
  • SLC2A1 protein, human