Diffusion enhancement of drugs by loaded nanoparticles in vitro.

1. Dalargin, a Leu-enkephaline analogue, does normally not pass the blood-brain barrier (BBB). When it was adsorbed onto the surface of polybutylcyanoacrylate, nanoparticles dalargin can cross the BBB and induce central analgesic effects after intravenously as well as after oral application. 2. The mechanisms of this effect are unknown. Therefore, the authors evaluated whether neuronal transport was involved in this effect. In hippocampal synaptosomes and in tissue slices in vitro the active neuronal uptake and diffusion processes were determined by use of labelled D-aspartate as a marker of the aspartate/glutamate transporter and orotic acid as marker of diffusion. 3. Transporter-mediated uptake into hippocampal tissue preparations was not altered in comparison to control whereas diffusion processes were enhanced. These data indicate that the nanoparticles can modify neuronal uptake mechanisms.