PEPTIDE-TRANSPORT ACROSS THE BLOOD-BRAIN-BARRIER

The progress in isolation and culturing techniques of cerebrovascular endothelial cells, which will be briefly reviewed, enabled the development of in vitro models of the blood-brain barrier. The in vitro models, which are by now extensively characterized and validated, can generally be applied to specific aspects of blood-brain barrier anatomy and physiology and can also offer a valuable tool in drug disposition studies. Application of the in vitro model to the specific question of peptide transport across the blood-brain barrier, offers numerous methodological advantages: basic physiological parameters can be controlled and different experimental setups, not available in the in vivo setup, can be applied, thereby offering means to obtain a more thorough understanding of the basic aspects and mechanisms responsible for peptide transport across the blood-brain barrier. This approach will be illustrated by means of studies performed on a vasopressin-like model-peptide and will be presented in perspective of in vivo studies performed with the same peptide. Potential application of the in vitro blood-brain barrier model also includes the field of transport enhancement of poorly transported drugs, a maybe essential prerequisite for further development of peptides into therapeutically beneficial drugs. © 1990.