Drug- and gene delivery to the brain is highly restricted by the vascular barriers of
the brain, denoted by the blood-brain barrier (BBB) and the blood-cerebrospinal
fluid (CSF) barriers. Among these barriers, BBB is the main limiting factor. It is
composed by the brain capillary endothelial cells (BCECs). The BCECs barrier
function is supported by astrocytes, pericytes and neurons to form the blood-brain
barrier. BCECs are very tightly connected to each other by tight junctions. Apart
from the essential substrates needed to nourish the brain, small and/or lipophilic
molecules are free to diffuse into the brain. However most pharmacologically
active drugs and gene fragments are too large to enter the brain. Various kinds of
drug-carriers have been constructed for delivery of large substances to the brain.
Such drug-carriers have to be able to successfully carry their cargo through the
BCECs and into the brain. For testing the ability of drug-carriers to deliver their
cargo into the brain, investigators have constructed different in vitro BBB models,
consisting of BCECs that express the main characteristics of the BBB in vivo.
In the first part of the thesis the ability of two drug-carriers, pullulanspermine
and SPIOs, to mediate transfection of BCECs or transcellular transport
through BCECs in vitro was studied.