Biomedical Engineering Reference
In-Depth Information
Inlet channel
Sheer force
Dispersing channel
Figure 23.5
(See companion CD for color igure.)
.Fluidic.nanoprecipitation.system.(FNPS).employing.PLGA.sample.inlet.
and.dispersing.channel.
accumulate.at.a.certain.capillary.after.intravenous.injection..Choosing.the.right.particle.
size. becomes. even. more. important. for. targeted. delivery. to. a. tumor. site.. It. is. generally.
believed. that. the. pore. size. of. tumor. is. below. 700.nm,. and. thus. nanoparticles. should. be.
smaller.than.that.for.eficient.delivery.at.tumor.site..Another.factor.to.consider.is.that.the.
RES.is.activated.following.the.opsonization.process,.emitting.the.signal.to.the.receptor.of.
the.macrophage..This.initiates.the.scavenger.to.engulf.the.nanoparticles.to.break.down.the.
particles.to.fragments..The.most.important.thing.is.that.nanoparticles.should.be.able.to.
escape.from.the.lysosome.in.which.the.pH.is.value.reduced.to.around.4.with.the.presence.
of.digestive.enzymes..If.the.particles.are.designed.to.be.dissolved.at.low.pH.in.lysosome,.
the. drug. could. diffuse. through. cytoplasm. (Gibaud. et. al.. 1996;. Mukherjee. et. al.. 1997)..
Introduction.of.a.hydrophilic.coating.to.nanoparticles.is.one.approach.of.avoiding.RES..The.
hydrophilic.part.of.the.polymer.has.to.be.long.enough.to.make.a.thick.layer.surrounding.
the. nanoparticles,. and. the. hydrophobic. area. needs. to. prevent. shear. detachment.. So. far,.
PEG.has.been.frequently.used.to.coat.the.outer.layer.of.nanoparticles.to.prolong.the.blood.
circulation.
23.3.2
.
Oral Delivery of Nanoparticles
Drug.delivery.by.oral.route.is.still.the.most.preferred.method.of.administration..Nano/
microparticles.are.believed.to.be.uptaken.from.the.gastrointestinal.(GI).tract.through.M.
cells.of.the.Peyer's.patches,.which.are.follicles.of.lymphoid.tissue.specially.composed.of.
epithelium. (Brayden. et. al.. 2005;. Hans. and. Lowman. 2002).. Nanoparticles. are. found. to.
employ.several.pathways,.such.as.passive.diffusion,.active.transportation.by.membrane,.
and.aqueous.channel.by.opening.tight.junction,.to.pass.through.the.gastrointestinal.bar-
rier..Thus,.after.transcellular.absorption.is.successfully.done.by.M.cells,.nanoparticles.can.
be.transported.to.lymphocytes.by.a.lymphatic.absorption.mechanism.and.have.a.greater.
chance.to.enter.systemic.circulation.
An.experiment.on.the.effect.of.size.on.GI.absorption.showed.that.PLGA.particles.with.
sizes.ranging.from.2.to.5.μm.remained.in.the.Peyer's.patches..On.the.other.hand,.particles.
smaller.than.2.μm.translocated.to.mesenteric.lymph.nodes.(Yeh.et.al..1998)..Permeability.
tests.were.done.by.using.Caco-2.cells..Mathiowitz.et.al..demonstrated.that.nanoparticles.
around. 100.nm. showed. considerable. uptake. that. is. 2.5. times. greater. than. that. of. a. 1.μm.
