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” agent.
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
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:
injected during medical procedures (or released from
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
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
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
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).