Biomedical Engineering Reference
In-Depth Information
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Figure 1.1
How accumulation in the tumor is possible. There is evidence for
fenestrations in tumor vasculature that allow some macromolecules to
extravasate. However, the extent of extravasation and intratumoral
distribution of macromolecules is debatable. Nanoparticle distribution is
affected by the vasculature, the ECM, interstitial fluid pressure, and the
presence of cells.
1.3.1 Challenges Present in the Carrier
In Ehrlich's day a ''magic bullet'' seemed an appropriate analogy for the vision
he had. Present-day scientists sometimes interpret this analogy to something
more akin to a homing missile. However, current targeting drug delivery
designs are not target-seeking as they cannot sense the target from a distance
and adjust their trajectory to home in on it. Furthermore, current designs are
not capable of self-propulsion. Instead, they are opportunistic in that they rely
on being carried to the target by convective blood flow and diffusion through
tissues. There are also challenges associated with the characteristics of the
carrier that can have an effect on its stability.
1.3.1.1
Challenges in Stability and Tumor Accumulation
As mentioned earlier, a carrier needs to be stable and this will have an effect on
safety and efficacy. For example, while a strongly positively charged molecule
aids in entering the cell, high doses of cationic carriers can be toxic.
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Essentially, the biocompatibility of the carrier is determined by the chemistry
of the monomer and degradation products.
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Viruses also serve as effective
carriers but have risks—one of which being an immune response against the
