Biomedical Engineering Reference
In-Depth Information
resonance. imaging. (MRI),. computed. tomography,. etc.),. can. all. be. engineered. through.
surface.functionality.carriage.of.the.nanocarriers. 10 .Despite.milestones.in.the.therapeu-
tic.medical.sector,.there.are.still.outstanding.issues..For.instance,.issues.related.to.the.
delivery. drugs. not. being. stable. in. the. environment. of. applications. have. been. shown.
as. a. major. drawback.. As. an. example,. the. oral,. noninvasive. delivery. of. drugs. fails. to.
deliver. enough. quantities. due. to. acids. in. the. stomach. and. also. the. resistance. of. the.
intestines,.which.alter.and.reduce.the.absorption.of.drugs..Also,.the.circulation.of.the.
drugs.in.the.system.for.enough.time.is.critical,.requiring.further.strategies.in.drug.for-
mulations..Another.issue.has.been.the.development.of.drugs.that.target.only.speciic.
areas.in.the.body..This.would.avoid.the.toxicity.of.drugs.that.occurs.as.a.result.of.their.
accumulation.in.healthy.tissue..In.general,.there.is.still.not.enough.information.regard-
ing.the.interactions.of.drugs.with.their.targets,.and.more.research.is.required.in.this.
area..Studies.of.the.fundamental.interactions.with.cells,.tissue,.and.in.vivo.models.are.
still.required.
24.2.2 Nanoparticle-Based Targeting Strategies
Poor. pharmacokinetics. and. biopharmaceutical. properties. of. the. majority. of. potential.
therapeutics.have.shown.the.need.for.the.development.of.delivery,.biolabeling,.and.diag-
nostic.systems.with.improved.eficacy.and.eficiency. 11 .The.noninvasive.manner.through.
which.preliminary.indings.have.indicated.nanoparticles.interact.with.biomolecules.on.
the.surface.of.cells.and.inside,.leaving.all.biochemical.behavior.intact,.has.strengthened.
the.case.for.a.nanoparticle-based.therapeutic.“toolbox.” 12 .A.careful.understanding.of.the.
processes.involved.in.the.interactions.of.nanoparticles.with.cells,.leading.to.their.uptake.
(or.rejection).and.their.subsequent.release,.is.of.crucial.importance..Nanoparticles.offer.
a.rare.opportunity.to.develop.multifunctional.therapeutics,.integrating.diagnostics.and.
therapeutic.functions.in.one.toolbox,.simultaneously.labeling,.monitoring,.and.deliver-
ing.drug.materials,.controlling.both.spatial.and.temporal.release.and.monitoring. 13
24.2.2.1   Mechanism of Uptake
Normally.the.uptake.of.particulate.matter.into.cells.is.by.either.phagocytosis.or.endocyto-
sis. 6 .Phagocytosis.is.usually.involved.in.the.uptake.of.particles.larger.than.500.nm,.a.path-
way.observed.in.macrophages,.dendritic.cells,.monosites,.and.basophils..Most.inorganic.
nanoparticles.are.synthesized.to.within.the.1-100.nm.range,.and.there.they.are.sought.to.
be.endocytosed.into.the.cell,.since.the.size.remains.at.less.than.200.nm.regardless.of.sur-
face.modiications..Endocytosis.can.be.either.receptor.mediated.or.nonreceptor.mediated,.
which.either.enhances.or.retards.the.uptake. 14,15 .The.uptake.can.be.viewed.as.a.result.of.
the.contest.between.the.thermodynamic.driving.force.for.wrapping,.which.refers.to.the.
amount. of. free. energy. needed. to. drive. the. nanoparticles. into. the. cell,. and. the. receptor.
diffusion.kinetics,.which.refers.to.the.kinetics.of.recruitment.of.receptors.to.the.binding.
cell. 16 .Targeting.of.cellular.diseases.such.as.cancer.in.cells.by.nanoparticle-based.systems.
is. subdivided. into. two. pathways:. (1). passive. and. (2). active. targeting.. Passive. targeting.
employs.pharmacokinetic.manipulation.and.nanoparticle.size.reduction,.whereas.active.
targeting. involves. speciically. targeting. areas. on. a. disease. cell. by. surface. modiications.
of.the.nanoparticles..This.targeting.seeks.to.address.the.current.shortfalls,.such.as.those.
observed.with.conventional.drugs.that.show.less.than.desired.accumulations.on.the.target.
or.disease.area.
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