Nanotoxicity - The Nanobiotechnology - page 613

necessary.for.this.receptor-mediated.uptake..Recent.results.showed.that.the.biocompatible.
PLGA. functionalized. with. the. peptide. NH 2 -Gly-l-Phe-d-Thr-Gly-l-Phe-l-Leu-l-Ser.
(O-β-d-Glucose)-CO-NH 2 . [g7]. is. a. useful. starting. material. for. the. preparation. of. g7-Np.
polymeric.nanoparticles.in.drug.delivery.to.the.central.nervous.system..It.has.been.veriied.
that.these.nanoparticles.can.cross.the.BBB.and.are.able.to.reach.all.of.the.examined.brain.areas.
including.the.cerebellum.parenchyma,.right.encephalon,.left.encephalon,.and.the.frontal.
encephalon.(Tosi.et.al..2007)..Overcoating.the.nanoparticles.with.polysorbates,.especially.
polysorbate.80,.can.promote.the.drug.transport.to.the.brain.areas..It.has.been.demonstrated.
that. polysorbate. 80-coated. polybutylcyanoacrylate. (P80-PBCA). nanoparticles. can. deliver.
the.peptide.into.the.central.nervous.system.to.induce.its.analgesic.effects;.however,.coating.
with.alternative.surfactants.did.not.produce.the.expected.effects.(Kreuter.et.al..2002)..It.is.
proposed.that.overcoating.with.these.materials.leads.to.the.adsorption.of.apolipoprotein,.
especially. ApoE,. from. the. blood. plasma. onto. the. surface. of. nanoparticles.. The. particles.
then.behave.like.low.density.lipoprotein.in.the.sense.of.mimicking.LDL.receptor-mediated.
transcytosis,.which.enhances.the.uptake.by.the.brain.endothelial.cells.with.nanoparticles.
and.carries.drugs.across.the.BBB..Subsequently,.the.drugs.may.be.released.into.the.cells.
and.transported.to.the.brain.interior.by.passive.diffusion.
It.has.been.accepted.that.nanoparticles.can.induce.oxidative.stress,.leading.to.the.gen-
eration. of. ROS. that. could. disrupt. the. BBB. and. cause. access. to. the. central. nervous. sys-
tem.(Chen.et.al..2008)..The.biodistribution.of.intravenously.administrated.gold.particles.
showed.that,.contrary.to.the.100.and.200.nm.particles,.the.15.and.50.nm.nanoparticles.can.
cross. the. BBB. and. enter. the. brain. (Sonavane. et. al.. 2008).. Intravenous. ceria. administra-
tion.into.rats.altered.oxidative.stress.indicators.and.antioxidant.enzymes.in.brain.tissues.
(Hardas. et. al.. 2010).. On. the. other. hand,. many. researchers. found. that. the. nose-to-brain.
transport.of.exogenous.materials.is.a.potential.route.for.bypassing.the.BBB.(Illum.2000,.
Oberdorster.et.al..2009)..For.instance,. 13 C.nanoparticles.can.transport.directly.from.olfac-
tory. epithelium. to. the. olfactory. bulb. via. the. olfactory. nerves. (Oberdörster. et. al.. 2004)..
Other.nanoparticles.including.gold.(De.Lorenzo.and.Darin.1970),.manganese.oxide.(Elder.
et.al..2006),.iridium-192.(Semmler.et.al..2004),.ferric.oxide.(Wang.et.al..2007),.copper.(Zhang.
et.al..2012),.and.titanium.dioxide.(Wang.et.al..2008a,b,.Zhang.et.al..2011).have.also.been.
reported. to. accumulate. in. the. olfactory. bulb. or. even. to. penetrate. deeply. into. the. brain.
and. induce. damage.. It. has. been. shown. that. copper. content. increased. gradually. in. the.
olfactory.bulb.with.the.increased.dose.of.intranasal.instillation.of.nano-copper;.however,.
no.obvious.changes.were.found.in.the.other.brain.regions..The.signiicant.change.in.neu-
rotransmitter. secretion. and. turnover. ratio. level. showed. that. the. normal. function. of. the.
whole.brain.was.disturbed.after.intranasal.instillation.of.nano-copper.(Zhang.et.al..2012)..
The.olfactory.bulb,.as.the.irst.target.site,.will.receive.the.earliest.and.highest.dose.follow-
ing. nasal. exposure.. It. is. proposed. that. a. unique. relationship. between. the. anatomy. and.
physiology.of.the.mammalian.nasal.and.cranial.cavity.tissues.leads.to.the.direct.delivery.
of.nanoparticles.into.the.brain.
The.retina.is.a.unique.neural.tissue.that.is.exposed.to.light.throughout.its.life.and.is.quite.
fragile.when.considering.the.possible.ocular.exposure.to.nanomaterials..Ocular.exposure.
might.occur.from.nanoparticles.that.are.airborne,.intentionally.placed.near.the.eye.when.
using. cosmetics,. accidently. splashed. onto. the. eyes,. or. by. transfer. from. the. hands. during.
rubbing.of.the.eyes..This.route.of.exposure.could.result.in.nanoparticles.being.retained.in.
the.eyes.or.in.drainage.from.the.eye.socket.into.the.nasal.cavity.and.entering.brain.by.nose-
to-brain. transport.. Recently,. several. preliminary. in. vitro. tests. showed. that. materials. that.
are.prone.to.induce.phototoxicity.have.a.potential.to.be.photo-neurotoxic.in.the.retina.and.
surrounding.tissues..TiO 2 .particles.were.phototoxic.in.vitro.following.ultraviolet.A.(UVA).