Cellular implants. What if you could dispense with all the intermediate steps between cell-culture production of a therapeutic molecule and
its delivery to the patient? In a process similar to creating drug microspheres for sustained parenteral or pulmonary delivery,
genetically engineered cells (often human skin or epithelial cells) can be encapsulated in cellulose sulfate or another biopolymer.
The encapsulated cells are then implanted under a patient's skin to form "neo-organs," which the body automatically provides
with vascularization like it often does with tumors. But this tiny invader helps the body rather than harms it.
The biopolymer encapsulation provides an immunoprotective barrier for the cells, allowing in only nutrients from the bloodstream
and allowing out only pure cell-secreted protein with the typical cellular waste products the body handles all the time. The
patient's body will not reject this "neo-organ" as foreign because there is no contact between its immune-response cells (such
as T-cells) and the encapsulated cells.
The Blood-Brain Barrier
|
The Blood-Brain Barrier
To protect the brain from infection and from damage that could be caused by foreign chemicals, the endothelial cell linings
of its capillaries are tightly packed together. Nothing but water can diffuse freely from the blood to the brain. Nutrients
are actively transported by cellular mechanisms across the blood-brain barrier (BBB). Most drugs are treated as foreign material
to be excluded from entering brain fluids. Only a few drugs can enter the brain at all. Much of the time this is beneficial;
many powerful drugs could cause trouble if they got past the BBB. But, what if the brain is already in trouble (it has a tumor,
for example), and the drugs need to get into its fluids to do their job?
Some drugs are chemically similar enough to brain nutrients (or can be made enough like them) that they can be moved into
the brain by the nutrient back door. Water-soluble substances are almost universally excluded from the brain. But fat-soluble
substances can dissolve across the membranes of endothelial cells and pass through them into the brain. So another method
of getting a drug across the BBB is to make it lipid soluble. With a protein, that can be a tall order. And if those chemical
methods won't work, there is currently only one other choice, and it can be risky.
Highly concentrated sugar solutions, when injected into the arteries that supply the brain, will force the endothelial cells
to shrink temporarily. That opens up gaps between them through which drugs injected immediately following can diffuse. Of
course, anything else that happens to be going by in the bloodstream at that time may get across the BBB as well, and that
makes this a risky approach. But sometimes — as in the treatment of brain tumors — the cure is worth the risk.
Biopharmaceutical developers are used to thinking in such terms. The field of risk assessment is about weighing the possible
benefits of a therapy or process step against its drawbacks. Meanwhile, product developers continue to work toward breaching
the BBB. Some methods under study include facilitated diffusion; receptor- or carrier-mediated transport using glycoproteins,
nucleosides, certain vitamins, iodine, or amino acids; and oligoglycerols.
|
