Abstract

An increasing number of studies demonstrate the ability of peptides to cross the blood-brain barrier (BBB), opening perspectives for a new class of therapeutics for central nervous system diseases. However, information on the BBB transport of peptides suffer from a wide variety in used methods and experimental set-up. Therefore, it is currently difficult, if not impossible, to classify peptides according to their BBB influx characteristics. To allow direct comparison of BBB influx results of peptides, we introduce a classification method and unified response for BBB influx transport of peptides. First, the results of BBB influx response types (i.e. K_in (MTR), Kin (Perfusion), P_{in vitro} and P_{in vivo}), which quantitatively express brain influx, were classified into five classes of BBB influx magnitude based on the distribution of these results for the individual response types. Then, these classes were converted to a BBB_in-response, representing a scaled value ranging from zero (no influx) to ten (high influx), independent from the BBB influx response type from which it was derived. This unified response can immediately be applied for new BBB influx results of peptides and represents a ballpark figure for BBB influx and allows direct comparison and ranking of peptides independent of the response type.

Keywords: Blood-brain barrier, classification, influx, peptides, permeability, unified response.

Graphical Abstract