In its neuroprotective role, the blood-brain-barrier
(BBB) blocks agents from entering the brain. This protective mechanism
has been in place since man first walked the earth. If this mechanism
was not in place, the brain would self-destruct within a few weeks,
as invaders, including natural sugars, foods, and amino acids,
would cause a biochemical implosion capable of killing the host
(the human body).
Getting helpful and therapeutic agents to cross
the BBB without allowing dangerous agents access to the delicate
brain-balance is a very intricate process involving many years
of specialized research, including extensive trial-and-error methods.
The key in Nanoengineering is to biochemically attach a therapeutic
agent combined with a nanoparticle in order to access one of the
four pathways. A nano-sized agent is small enough to cross the
blood-brain-barrier, as long as it is a “brain-friendly”
Plant glycosides can be engineered to cross the
blood-brain-barrier attached to a therapeutic agent, such as the
amino acid L-arginine. Currently, the only known and proven technology
for glycoside engineering that encompasses Nanotechnology is Trutina
Dulcem, a 32-step process involving the removal of glycosides
from organic kiwi fruit.
Since a nanoparticle is incredibly small, a delicate
proprietary extraction process is required to produce glycosides
that can attach to an amino acid molecule, and transport it safely
over the blood-brain-barrier. Nanoparticles possess a diameter
small enough to penetrate through diminutive capillaries into
the cell's internal machinery (3) and create a pre-programmed
response, thus the term Edible Computer Chip.
NANOPARTICLE PATHS OF ENTRY
There are only four distinct paths of entry that
allow Nanoparticles to enter the human body. The four entry routes
for nanoparticles into the body are:
2) Swallowed (oral entry)
3) Absorbed through skin
4) Deliberately injected during medical procedures
(or released from implants)
The blood-brain barrier blocks all
molecules except those that cross cell membranes by means of lipid
solubility (such as oxygen, carbon dioxide, ethanol, and steroid
hormones) and those that are allowed in by specific transport
systems (such as some amino acids).
Once within the body they are highly
mobile, and in some instances, can be engineered to
cross the blood-brain barrier (BBB). The blood-brain
barrier (BBB, also known as the blood-cerebrospinal
fluid barrier) is a membrane that controls the passage
of substances from the blood into the central nervous
system. The BBB is a physical barrier between the
local blood vessels and most parts of the central
nervous system itself, and stops many substances from
traveling across it (2).
the body, the walls of the capillaries (the smallest
of the blood vessels) are made up of endothelial cells
separated by small gaps. These gaps allow soluble
chemicals within tissues to pass into the blood stream,
where they can be carried throughout the body, and
subsequently pass out of the blood into different
tissues. In the brain, these endothelial cells are
packed more tightly together, due to the existence
of zonulae occludentes (tight junctions) between them,
blocking the passage of most molecules (2).
L-ARGININE TRANSPORT SYSTEMS
Only a Specific Transport System will allow the
amino acid L-arginine to cross the blood-brain-barrier. Carrier-mediated
transporters, such as the amino acid carrier Trutina Dulcem, is
an Nanoparticle biostrategy designed to allow transport across
the blood-brain-barrier. Other methodologies for BBB transport
include receptor-mediated transcytosis for insulin or transferrin;
and blocking of active efflux transporters such as p-glycoprotein.
With new methodologies heretofore unavailable
to scientists, Nanoparticles will now take their respective place
in the medical and science fields, particularly in the field of
chemotherapy drug delivery.
Strategies for drug delivery behind the BBB include
intracerebral implantation and convection-enhanced distribution.
Substances with a molecular weight higher than 500 daltons (AMUs)
generally cannot cross the blood-brain barrier, while
smaller molecules often can, thus elucidating the complexity of
creating a Nanoparticle that can cross the BBB.
Many drugs are unable to pass the barrier, since
98 percent of them are heavier than 500 daltons. In addition,
the endothelial cells metabolize certain molecules to prevent
their entry into the central nervous system; the most-studied
example of this is L-DOPA (2).
The blood-brain barrier protects the brain from the many chemicals
flowing around the body. Many bodily functions are controlled
by hormones, which are detected by receptors on the plasma membranes
of targeted cells throughout the body.
The secretion of many hormones are controlled
by the brain, but these hormones generally do not penetrate the
brain from the blood, so in order to control the rate of hormone
secretion effectively, there are specialized sites where neurons
can "sample" the composition of the circulating blood.
At these sites, the blood-brain barrier is 'leaky'; these sites
include three important 'circumventricular organs', the subfornical
organ, the area postrema and the organum vasculosum of the lamina
terminalis (OVLT) (2).
The blood-brain barrier (BBB) is an effective
way to protect the brain from common infections and invaders that
cause brain-imbalances, such as L-Lysine blocking L-Arginine from
crossing the BBB. If the wrong agents are allowed to cross the
BBB, or to piggy-back on agents that cross the BBB, serious brain
infections can occur, which are very difficult to treat or cure.
As such, it is imperative that therapeutic agents,
whether amino acids or drugs, are Nanoengineered to cross the
blood-brain-barrier unobstructed, and without carrying dangerous
agents into the brain.
In its neuroprotective role, the blood-brain barrier
functions to hinder the delivery of many potentially important
diagnostic and therapeutic agents to the brain. Therapeutic molecules
and genes that might otherwise be effective in diagnosis and therapy
do not cross the BBB in adequate amounts.
Mechanisms for drug targeting in the brain involve
going either "through" or "behind" the BBB.
Modalities for drug delivery through the BBB entail disruption
of the BBB by osmotic means, biochemically by the use of vasoactive
substances such as bradykinin, or even by localized exposure to
ultrasound. The potential for using BBB opening to target specific
agents to brain tumors has just begun to be explored (2).