Biomedical Engineering Reference
In-Depth Information
8.7 Summary
Nanoparticle. formulation. has. great. advantages. over. conventional. drug. formulations,.
resulting.in.a.sustained.and.controlled.manner.for.drug.release,.thus.increasing.the.thera-
peutic. effect. and. reducing. side. effects.. Size. and. surface. modiications. are. the. two. key.
factors.determining.the.performance.of.biodegradable.polymeric.NPs.for.cancer.therapy..
Targeted.chemotherapy.can.be.realized.by.functionalization.of.the.NP.surface.by.target-
ing.ligands.such.as.monoclonal.antibodies..A.copolymer.strategy.can.be.further.employed.
to.synthesize.nanoparticles.of.two.component.copolymers:.one.component.copolymer.has.
ideal.HLB.for.high.drug.encapsulation.eficiency,.high.cellular.adhesion,.and.internaliza-
tion,.and.another.copolymer.facilitates.the.conjugation.of.the.ligand.molecules.on.the.NP.
surface..The.targeting.effects.can.thus.be.quantitatively.controlled.by.adjusting.the.blend.
ratio. between. the. two. copolymers.. Development. of. multifunctional. NPs. is. also. feasible.
by. coencapsulation. of. the. imaging,. therapeutic,. and. reporting. agents. in. the. polymeric.
nanoparticles,.with.their.surface.functionalized.by.targeting.ligands..In.this.chapter,.we.
provided. a. preliminary,. proof-of-concept. investigation. for. a. targeted. drug. delivery. sys-
tem.of.molecular.probe-conjugated.nanoparticles.of.a.blend.of.two.biodegradable.copoly-
mers,.PLA-TPGS.and.TPGS-COOH..It.was.found.that.judged.by.in.vitro
cellular.mortality,.
the. trastuzumab-functionalized. PLA-TPGS/TPGS-COOH. NP. formulations. of. docetaxel.
can. be. 1.215-,. 1.215-,. and. 1.073-fold. for. MCF-7. cells. and. 1.697-,. 1.886-,. and. 1.126-fold. for.
SK-BR-3. cells. more. effective. than. the. PLA-TPGS/TPGS-COOH. NP. formulation. with. no.
trastuzumab.functionalization.after.24,.48,.and.72.h.treatment,.respectively..The.targeting.
effects.of.trastuzumab.functionalization.thus.showed.39.7,.55.2,.and.4.9%.higher.cancer.cell.
mortalities.for.SK-BR-3.cells.of.high.HER2.overexpression.than.for.MCF-7.cells.of.moder-
ate.HER2.overexpression.after.24,.48,.and.72.h.treatment,.respectively..The.strategy.greatly.
simpliied.the.existing.nanoparticle.technologies.for.targeted.drug.delivery.
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