Nanotechnology Meets the Blood-Brain Barrier
anotechnology is helping drug devel-
opers to circumvent a problem in
drug delivery based on an anatomical
impediment—the close attachments of the cells
that form tiny blood vessels in the brain. Like a
tight line of police officers keeping out a crowd,
the blood-brain barrier is a vast network of capil-
laries in the brain whose cells are F
rmly attached
by overlapping tight junctions. These cells also
lack the scattered vesicles and windowlike clefts
in other capillaries. In addition, star-shaped brain
cells called astrocytes wrap around the barrier.
The 400-mile blood-brain barrier shields
brain tissue from toxins and biochemical ±
tions that could be overwhelming. It also allows
selective drug delivery. Certain antihistamines,
for example, do not cause drowsiness because
they cannot breach the barrier. But this protec-
tion has a trade-off—the brain cannot take up
many therapeutic drugs that must penetrate to
be e²
³or decades researchers have attempted to
deliver drugs across the barrier by tagging com-
pounds to substances that can cross, designing
drugs to fit natural receptors in the cell mem-
branes of the barrier, and injecting substances
that temporarily relax the tight junctions. More
recently, researchers have applied nanotech-
nology to the problem of circumventing the
blood-brain barrier. Nanotechnology is the
application of structures smaller than 100 bil-
lionths of a meter (100 nanometers) in at least
one dimension.
Nanoparticles that can cross the blood-brain
barrier are made of combinations of oils and poly-
mers, with a neutral or slightly negative charge
(positively charged particles are toxic). In one
application, anesthetics or chemotherapeutics
are loaded into fatty bubbles (liposomes) that are
in turn placed in nanoparticles. This delivery sys-
tem masks the part of the drug that cannot cross
the barrier and slows release of the drug, which
diminishes side e²
In another application, insulin is delivered
in inhaled nanoparticles 10 to 50 nanometers in
diameter. Originally developed to provide insu-
lin to people with diabetes instead of injecting
it, clinical trials are showing that it is also helpful
in maintaining memory in people who have mild
cognitive impairment or Alzheimer disease.
As a rule, epithelial tissues lack blood vessels. However,
nutrients diffuse to epithelium from underlying connective
tissues, which have abundant blood vessels.
Epithelial cells readily divide, so injuries heal rapidly
as new cells replace lost or damaged ones. Skin cells and
the cells that line the stomach and intestines are continually
being damaged and replaced.
Epithelial cells are tightly packed. In many places, des-
mosomes attach one to another, enabling these cells to form
effective protective barriers in such structures as the outer
layer of the skin and the inner lining of the mouth. Other epi-
thelial functions include secretion, absorption, and excretion.
Epithelial tissues are classi±
ed according to the shape
and number of layers of cells. Epithelial tissues composed of
thin, fl
attened cells are
those with cubelike cells
and those with elongated cells are
Epithelium composed of a single layer of cells is
with two or more layers of cells,
In the following
descriptions, modi± cations of the free surfaces of epithelial
cells refl
ect their specialized functions.
List the general characteristics of epithelial tissue.
Explain how epithelial tissues are classiF
Tight junction
Cell membrane
Cell membrane
Cell membrane
Gap junction
Some cells are joined by intercellular junctions, such as
tight junctions that fuse neighboring cell membranes, desmosomes
that serve as “spot welds,” or gap junctions that allow small molecules
to move between the cytoplasm of adjacent cells.
Cancer cells secrete a substance that dissolves basement membranes,
enabling the cells to invade tissue layers. Cancer cells also produce
fewer adhesion proteins, or none at all, which allows them to spread
into surrounding tissue.
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