Biomedical Engineering Reference
In-Depth Information
body. In some instances, the metabolites of the drugs are active. Therefore, the drug would
need to make it to an organ that can metabolize the drug, usually the liver, and then the
metabolites are transported through the vascular system to have an effect. In general, the
drug or its metabolites are then removed by the liver or the kidneys. The importance of
drug delivery is that the size of drug molecules and the molecular weight of drug mole-
cules is typically larger than the usual molecules transported through these mechanisms.
Combined with this, the permeability and diffusion coefficient can be significantly lower
than other molecules. Therefore, the design of drugs, including their mode of delivery,
need to be carefully considered in order to ensure proper delivery.
It is also important to differentiate between diffusion, active transport, cellular trans-
port, and organ level transport. We discussed diffusion in
Section 7.1
, and we will relate
this to the more physiological transport mechanisms. Active transport requires the pres-
ence of a particular receptor within the cell membrane. These receptors are proteins that
function to transfer signals, possibly in the form of molecules, from one side of the mem-
brane to the other (for clarification, this also includes transfer across the nuclear membrane
and other organelle membranes). Under most conditions, the binding of the ligand, which
is the molecule that will be transported, to the receptor, induces a conformational change
in the protein structure of the receptor. This change can either cause the ligand to be
brought into the cell or signal a cascade that may result in a cellular level functional
change. Most receptor-ligand events can be described by kinetic reactions that describe the
association and the dissociation of the receptor-ligand complex. Depending on the magni-
tude of the association rate constant as compared to the dissociation constant, the outcome
of these kinetic events will be determined. At the cellular level, transport of molecules will
either occur via diffusion through the cytoplasm or a coupled diffusion, where the mole-
cule of interest is associated with some other molecule (think of motor proteins). This has
been discussed previously, but the only new considerations would be that the diffusion
coefficients would differ because the medium that the molecules are moving through are
different.
Organ level transport is actually fairly intuitive to model; however, in practice the infor-
mation that is necessary to complete this type of modeling is typically missing. For
instance, the exact blood/lymph flow characteristics would need to be known for the
organ that is being modeled. If we assume a Krogh type of model, with uniform or some
clearly defined spacing, then this may be known. However, the fluid velocity through
each of these blood vessels would need to be known, and as we have learned earlier, fluid
velocity differs temporally and each capillary is not fully perfused at one instant in time.
Therefore, many simplifications would be needed to determine the location of blood ves-
sels along with the flow rate of blood through those vessels, over some period of time. The
second issue that complicates the modeling of molecules at the organ level is that perme-
ability, diffusion coefficients, and other transport phenomena are generally not known
along the entire path. We may be able to develop a formulation that simplifies this trans-
port (recall oxygen transport as discussed in
Section 7.1
), but then the accuracy of the solu-
tion may vary greatly. Also, the diffusion properties depend on the homogeneity of the
tissues/organs and as we can imagine, there is a significant amount of inhomogeneities in
biological specimens. The last issue with organ level transport, which confounds the solu-
tion methods, is that multiple length and time scales are involved in the transport. If we
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