Biomedical Engineering Reference
In-Depth Information
but.luctuate.because.of.distribution,.metabolism.and.excretion..Drug.delivery.systems.try.
to. overcome. this. problem. by. releasing. the. drug. with. zero-order. kinetics.. These. systems.
attain.desired.plasma.levels.and.sustain.the.release.of.the.drug.for.a.given.period.of.time..
Zero-order.release.has.the.advantage.of.maintaining.constant.plasma.levels,.and.therefore.
decreases. the. risks. of. toxicity. and. ineffectiveness..Another. problem. associated. with. the.
conventional.systems.is.exempliied.in.cancer.therapy..Most.conventional.chemotherapies.
are. relatively. nonspeciic;. for. example,. any. chemotherapeutic. drug. that. is. administered.
intravenously.enters.systemic.distribution,.and.this.results.in.the.exposure.of.healthy.cells.
to.the.toxic.chemical.alongside.the.target.cells. 3 .Targeted.DDS.have.therefore.been.devel-
oped.to.solve.these.problems.by.providing.drugs.with.the.predetermined.concentration.
mainly.at.the.target.site.
Another.reason.for.constructing.a.drug.delivery.system.is.that.sometimes.the.bioactive.
agent.is.very.unstable.and.has.the.risk.of.losing.its.bioactivity.due.to.the.environmental.
conditions.
The.therapeutic.strategy.of.drug.delivery.systems.has.to.take.into.account.many.factors,.
such.as.the.disease.type,.the.route.of.administration,.the.properties.of.the.drug,.and.the.
target.site.to.achieve.the.highest.eficacy.with.the.therapeutic.agent..The.main.aims.for.a.
drug.delivery.system.are.to 4
•. Protect.the.drug.from.the.host.by.minimizing.its.degradation,.prolonging.its.bio-
availability.after.administration
•. Protect.the.host.from.the.toxic.effects.and.side.effects.of.the.drug.due.to.accumula-
tion.at.the.desired.site.via.speciic.or.nonspeciic.interactions
•. Use. responsiveness. to. local. stimuli,. such. as. abnormal. local. pH. values. or. local.
temperatures,.to.achieve.the.kinetics.needed
Delivery.can.be.made.more.effective.by.targeting.actively.or.passively..For.active.target-
ing,.the.carrier.system.or.the.therapeutic.agent.can.be.conjugated.with.a.ligand.speciic.to.
the.target.tissue.or.target.cell.type..One.of.the.mechanisms.of.passive.targeting.to.a.tumor.
site.utilizes.the.properties.of.vasculature.at.the.tumor..Tumor.vasculature.has.a.chaotic.
structure,. which. consists. of. various. loops,. dead. ends,. and. openings,. and. has. increased.
leakiness.. Additionally,. because. the. lymphatic. drainage. is. hampered,. the. drug. carrier.
construct. stays. longer. at. the. tumor. site. 5 . These. two. factors. are. combined. and. result. in.
an.enhanced.permeability.and.retention.(EPR).effect. 6 .Macromolecules.and.nanoparticles.
take.advantage.of.the.EPR.effect.and.can.passively.be.targeted.to.the.tumor.site..Targeting.
of.the.therapeutic.agent.reduces.systemic.levels.and,.thus,.systemic.toxicity.and.achieves.
high.drug.levels.at.the.desired.site. 1
Responsive.drug.delivery.systems.use.the.advantage.of.on-demand.or.passive.triggering.
of.the.release.of.therapeutic.agents.using.a.local.characteristic.of.tissues.(low.pH,.high.tem-
perature).or.an.external.stimulus.(heat,.light,.temperature,.or.magnetic.ield). 4 .For.example,.
in.cancer.therapy.the.tumor.microenvironment.has.a.reduced.pH, 7 .increased.temperature,.
and.increased.oxidative.potential, 8 .and.these.environmental.factors.are.used.to.trigger.the.
release.of.drug.at.the.tumor.site.
Drug. delivery. systems. need. to. take. into. account. the. route. of. administration. in. order.
to. maximize. the. amount. of. drug. at. the. site. of. action.. Different. routes. of. administration.
require.different.conditions.for.successful.drug.delivery..Table 11.1.shows.the.routes.for.the.
administration.of.drug.delivery.systems.and.the.biological.systems.they.interact.with.
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