Recent developments in peptide drug delivery to the brain

Pharmacol Toxicol. 1992 Jul;71(1):3-10. doi: 10.1111/j.1600-0773.1992.tb00512.x.


Peptide-based therapeutics are highly water-soluble compounds that do not readily enter brain from blood owing to poor transport through the brain capillary endothelial wall, i.e., the blood-brain barrier (BBB). Strategies available for peptide drug delivery to brain include: (a) neurosurgical-based (intraventricular drug infusion, hyperosmotic opening of the BBB); (b) pharmacological-based (peptide lipidization, liposomes); and (c) physiological-based (biochemical opening of the BBB, chimeric peptides). Chimeric peptides are formed by the covalent coupling of a pharmaceutical peptide (that is normally not transported through the BBB) to a brain transport vector that undergoes absorptive-mediated or receptor-mediated transcytosis through the BBB. The most efficient brain transport vector known to date is a monoclonal antibody to the transferrin receptor, and this vector achieves a brain volume of distribution approximately 18-fold greater than the plasma space by 5 hr after a single intravenous injection of antibody. The chimeric peptides are formed generally with chemical-based linkers. However, avidin/biotin-based linkers allow for high yield coupling of drug to vector, and for the release of biologically-active peptide following cleavage of the chimeric peptide linker. These strategies may also be used for the delivery of antisense oligonucleotide-based therapeutics to brain. In conclusion, the development of efficacious neuropharmaceuticals in the future will require the development of both drug delivery and drug discovery strategies that operate in parallel.

Publication types

  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Animals
  • Antibodies, Monoclonal / administration & dosage
  • Biological Transport, Active
  • Blood-Brain Barrier / drug effects
  • Brain / drug effects*
  • Chimera
  • Drug Carriers
  • Drug Delivery Systems*
  • Humans
  • Oligonucleotides, Antisense
  • Peptides / administration & dosage*
  • Receptors, Transferrin / metabolism


  • Antibodies, Monoclonal
  • Drug Carriers
  • Oligonucleotides, Antisense
  • Peptides
  • Receptors, Transferrin