Biomedical Engineering Reference
In-Depth Information
the BBB and into peripheral tissues. The outcome of the route was found
to be quite effective in delivery of drugs to the brain when administered
using a suitable carrier system like polymeric depots, liposomes or lipid car-
riers. Several drugs like hexapeptide dalargin, doxorubicin, loperamide, and
tubocurarine have been successfully delivered to the brain, using polysorbate
80-coated nanoparticles intravenously.
Intra-arterial administration allows the drug to access the brain vascu-
lature before it enters peripheral tissue, by avoiding first pass metabolism.
It is a form of regional delivery to brain tumors, designed to enhance the
intra-tumoral concentrations of a given drug. An effective anticancer effect
was achieved with intra-arterial administration of a p53 (tumor suppressor
gene) containing adenoviral vector in a model of human malignant glioma
[203]. The basic mechanism behind the bioavailability of the drug in the
brain may be due to movement of the drug in capillaries, then to choroid
plexus epithelium, and finally reaching CSF, or by falling into arterial blood
and then going to CSF through white matter and a perivascular pathway.
A trans-nasal route has been utilized for delivering drugs for systemic
action, by crossing the nasal mucosa. The respiratory region of the nose is
considered to be the major site for drug absorption into the systemic circu-
lation, where the compounds can be absorbed by transcellular pathways or
paracellular passive absorption, carrier-mediated transport, and absorption
through transcytosis pathways. In the brain, a better targeting action can be
achieved, due to direct movement of the drug from the sub mucosa space
of the nose into the CSF compartment of brain [23]. The highly permeable
nasal epithelium allows rapid drug absorption to the brain, due to high total
blood flow, porous endothelial membrane, large surface area and avoidance
of first-pass metabolism. Many agents, active in the CNS, are more effective
when given nasally, and provide the advantage of small dose, self adminis-
tration and avoidance of sterile techniques. Transnasal delivery has some
limitations including damage of the nasal mucosa on frequent use of this
route, rapid clearance from the nasal cavity by mucociliary clearance system,
interference due to nasal congestion, elimination of some quantity of the
drug absorbed systemically via the normal clearance mechanism, and the
possibility of partial degradation or irritation to the nasal mucosa [204].
6.1.2 Physiological approaches
The brain requires essential substances for metabolism and survival, such as
glucose, insulin, growth hormone, low density lipoprotein, etc. These sub-
stances are recognized by specific receptors or transport mechanisms, result-
ing in specific transport into the brain. Therefore, the most effective way of
delivering neuro-active drugs is via transporters or internalizing receptors.
Drugs can be modified to take advantage of native BBB nutrient transport
systems, or by conjugation to ligands that recognize receptors expressed at
the BBB. Receptor and adsorptive mediated transcytosis has provided the
