Enhanced uptake of gH625 by blood brain barrier compared to liver in vivo: characterization of the mechanism by an in vitro model and implications for delivery.

We have investigated the crossing of the blood brain barrier (BBB) by the peptide gH625 and compared to the uptake by liver in vivo. We clearly observed that in vivo administration of gH625 allows the crossing of the BBB, although part of the peptide is sequestered by the liver. Furthermore, we used a combination of biophysical techniques to gain insight into the mechanism of interaction with model membranes mimicking the BBB and the liver. We observed a stronger interaction for membranes mimicking the BBB where gH625 clearly undergoes a change in secondary structure, indicating the key role of the structural change in the uptake mechanism. We report model studies on liposomes which can be exploited for the optimization of delivery tools.