Biomedical Engineering Reference
In-Depth Information
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Figure 1.2
Illustration of the concept that probability plays a bigger role than
targeting components. (A) The pyramid represents the accessibility to the
different organs based on tissue size and ability to uptake different sized
particles. (B) The Gaussian curve represents how the polydispersity of
the carrier will result in a range of sizes. The carrier can start out with a
low polydispersity index (1), but aggregate to become larger and more
polydisperse (2 and 3).
of these drug carriers is important, as it directly affects the polydispersity and
biodistribution of these particles.
1.3.1.2 Challenges in Targeting Mechanisms
Long circulation is also desired to benefit affinity-based targeting. Targeting
moieties that bind to overexpressed proteins are used to give the drug
specificity to the cancer to create the precision of the magic bullet. However,
some studies have shown that carriers with targeting ligands are more limited
in tumor penetration.
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It is likely that these ligands experience more binding
events that inhibit diffusion. On the other hand, more specific targeting with
monoclonal antibodies for HER2 has been shown to increase tumor
internalization.
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Unfortunately, it is sometimes difficult, yet very important,
to find cell surface proteins that are exclusive to the cancer. As discussed
earlier, antigen exclusivity was part of the problem that Mylotarg
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faced.
Furthermore, it was assumed that targeting HER2 could direct drug delivery
to cardiac tissues that express HER2 as part of repair.
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Eligibility for
HER2 treatment involves checking the levels of overexpression of these surface
proteins and assigning a score. However, for the highest score of 3+ the FDA
