Page 573 - Book Hosokawa Nanoparticle Technology Handbook

29 DELIVERY TO THE BRAIN APPLICATIONS

neuron

Polysorbate-
coated
nanosphere

astrocyte
5

Blood
ApoE
drug
1
2
endothelium with
tight junctions
pericyte
4 3
P-glycoprotein

ApoE receptor

Figure 29.2
Hypothetical mechanism of drug delivery to the brain by means of polysorbate 80-coated polyalkylcyanoacrylate PACA
nanospheres.
by injection of methotrexate via the carotid artery. The interaction between poloxamer 188-coated
Conventionally, the drug delivery for brain targeting nanoparticles and brain endothelial cells might be
has been carried out by injecting it into the vein. The weakened by this rapid elimination. On the other
authors evaluated the effect of the administration route hand, polysorbate 80-coated nanoparticles after injec-
of the surface-modified nanoparticle with polysorbate tion into the carotid artery and into the jugular vein
80, poloxamer 188 and chitosan on brain distribution showed higher brain distribution percentage com-
percentage and blood concentration (Fig. 29.3). pared with other modified nanoparticles. These results
All types of nanoparticles after injection via the consist with the data obtained by Kreuter’s group.
carotid artery showed higher brain-distribution per- Furthermore, polysorbate 80-coated nanoparticles had
centage than that after the jugular vein injection. prolonged circulation in blood compared with other
Elimination rate of uncoated nanoparticles was the nanoparticles. This long circulating effect might be
fastest among the nanoparticles evaluated. Remaining one of the factors for increasing the brain distribution
percentage of uncoated nanoparticles in the brain by the avoidance of uptake by RES.
reduced to 25% at 15 min after injection. At that time, Although the rapid clearance from blood circulation
the brain distribution percentage of the uncoated occurred, chitosan-coated nanoparticles prolonged
nanoparticles after the carotid artery injection was their retention in brain. Furthermore, the concentra-
almost corresponding to that after the jugular vein tions of nanoparticles in brain and their retention
injection. Furthermore, the elimination rate of behavior were not changed by the change in injection
uncoated nanoparticles in the blood was the fastest dose. Chitosan-coated nanoparticles prolonged their
among the evaluated nanoparticles. According to retention on the brain blood capillary by their adher-
these results, uncoated nanoparticles might not inter- ence to endothelial cell with electrostatic interaction,
act with the brain endothelial cell and were not taken whereas unabsorbed particles were eliminated rapidly
from the blood stream. from blood circulation by the uptake in RES.

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