Biomedical Engineering Reference
In-Depth Information
immunosuppressive soluble factors as TGF-b, IL-10, VEGF or COX-2 that can
make the vaccine ineffective (Kalinski
2009
).
In agreement with the extremely potency required for an oral cancer vaccine to
be effective, the previous literature usually proposed the use of recombinant and
attenuated bacteria and viral vectors expressing TAA that naturally infect oral
mucosa like Salmonella (Zhu et al.
2010
) or Papilomavirus and/or are also able to
invade others organs following oral inoculation like plant virus nanoparticles (Rae
et al.
2005
). The attributes adhesion, invasion and danger signalization are naturally
presented in these natural carriers and should be molecularly defined for the entire
synthetic construction in artificial cancer nanovaccines. It must be feasible and in
fact, either administered by oral or subcutaneous route, a nanoemulsion encapsulating
MAGE1-HSP70 and SEA complex protein was able to delay tumor growth and defer
tumor occurrence of mice challenged with B16-MAGE-1 tumor cells. The encap-
sulation of the Ag complex in nanoemulsion was significantly more important for the
oral than s.c. administration, indicating the importance of nanocarrier in mucosal
vaccination (Ge et al.
2009
). However, most mice-tumor models usually did not
recreate the complexity and immunosupressive environment found in human tumors.
5
Conclusions and Future Perspectives
The gut performs a hurt locker to cancer therapy. In this moment, none strategy is
able to target an anticancer drug specifically to distant cancer cells after oral adminis-
tration. However, we have made some progress and pharmaceutical nanodevices
have shown certain ability to improve the oral bioavailability of anticancer drugs by
overcoming solubility problems, exerting protection from degradation, prolonging
their interaction with the mucosa, bypassing P-glycoprotein extrusion and the first-
pass metabolism and facilitating translocation of the drug through the epithelia
from the gut lumen to the blood or lymph.
The physicochemical characteristics of the particles, mainly size, surface and
specific targeting, will critically determine the principal route of adsorption (if it
takes place) and their final outcome although the most documented and common
route of uptake is via the M-cell rich layer of Peyer's patches. The possibility of
transport across the intestinal epithelial cells would be restricted to very small
particles (50-100 nm). Either uptake by enterocytes or M-cells, particles eventually
reach the mesenteric lymph nodes, but there are no evidences of further spread.
Thus, the anticancer drug will be released from the carrier and will arrive into the
bloodstream since the lymphatic system avoiding the passage through the liver.
This route of delivery could enhance the bioavailability of anticancer drugs with
high first-pass metabolism or to be useful for improving the local accumulation of
therapeutics in intestinal lymph nodes.
Nanoparticles that attach to the surface of the enterocytes (without uptake) and,
if necessary, avoid P-gp extrusion and CYP metabolism could increase the absorption
of the free drug directly to the blood or lymph. This strategy should be preferable
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