Targeting receptor-mediated transport for delivery of biologics across the blood-brain barrier

Annu Rev Pharmacol Toxicol. 2015;55:613-31. doi: 10.1146/annurev-pharmtox-010814-124852. Epub 2014 Oct 8.


Biologics are an emerging class of medicines with substantial promise to treat neurological disorders such as Alzheimer's disease, stroke, and multiple sclerosis. However, the blood-brain barrier (BBB) presents a formidable obstacle that appreciably limits brain uptake and hence the therapeutic potential of biologics following intravenous administration. One promising strategy for overcoming the BBB to deliver biologics is the targeting of endogenous receptor-mediated transport (RMT) systems that employ vesicular trafficking to transport ligands across the BBB endothelium. If a biologic is modified with an appropriate targeting ligand, it can gain improved access to the brain via RMT. Various RMT-targeting strategies have been developed over the past 20 years, and this review explores exciting recent advances, emphasizing studies that show brain targeting in vivo.

Keywords: antibody; biologics; blood-brain barrier; insulin receptor; low density lipoprotein receptor; receptor-mediated transport; transferrin receptor.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Animals
  • Biological Products / administration & dosage
  • Biological Products / chemistry
  • Biological Products / metabolism*
  • Biological Transport
  • Blood-Brain Barrier / metabolism*
  • Capillary Permeability
  • Chemistry, Pharmaceutical
  • Drug Carriers*
  • Humans
  • Receptors, Cell Surface / metabolism*
  • Technology, Pharmaceutical / methods


  • Biological Products
  • Drug Carriers
  • Receptors, Cell Surface