Biomedical Engineering Reference
In-Depth Information
8.2.1 Nanoparticle Properties and Emulsifiers
Physicochemical.properties.of.nanoparticles.would.determine.in.vitro.and.in.vivo.perfor-
mances.of.the.nanoparticles..These.properties.include.particle.size.and.size.distribution,.
surface.morphology,.surface.chemistry,.surface.charge,.surface.adhesion/erosion,.drug.dif-
fusivity,.drug.encapsulation.eficiency,.drug.stability,.drug.release.kinetics,.etc..Several.fac-
tors.inluencing.an.optimal.design.of.nanoparticles.include.the.polymer.type.as.well.as.the.
molecular. weight,. the. copolymer. blend. ratio,. the. type. of. organic. solvent,. the. emulsiier/
stabilizer,.the.oil-to-water.phase.ratio,.the.mechanical.strength.of.mixing,.temperature,.pH,.
etc..Among.these,.the.polymer.type,.that.is,
its.molecular.structure.and.molecular.weight,.
and.the.copolymer.blend.ratio.are.the.major.factors.in.determining.the.degradation.rate.of.
the.nanoparticles,.and.thus.the.in.vitro.and.in.vivo.release.of.the.encapsulated.drug.
Emulsiiers,.the.macromolecules.that.are.added.in.the.emulsiication.process.for.nano-
particle.preparation,.play.an.important.role.in.stabilizing.the.colloidal.suspension.during.
nanoparticle. fabrication.. The. amphiphilic. emulsiier. molecules. are. supposed. to. stay. at.
the.oil-water.interface.to.decrease.the.interfacial.tension,.that.is,.the.nanoparticle.surface.
energy.per.unit.area,.to.facilitate.the.nanoparticle.formation.
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.Poly(vinyl.alcohol).(PVA).has.
been.preferentially.chosen.as.an.emulsiier.in.nanoparticle.fabrication.due.to.its.excellent.
stabilizing.ability.to.avoid.particle.aggregation.during.postpreparative.steps.(e.g.,.freeze-
drying.and.purifying),. high.yield.of.dry.particle. powder,.and.ease.to.be.redispersed. in.
solution. after. lyophilized.
7
. It. has. also. been. found,. however,. that. PVA. may. be. adsorbed.
or.tightly.associated.with.the.surface.layer,.and.thus.cannot.be.completely.removed.from.
the. surface. of. nanoparticles.
8-10
. Therefore,. PVA. should. not. be. used. as. an. emulsiier. in.
the.preparation.of.nanoparticle.formulation.for.intravenous.(i.v.)
administration,.although.
its. safety. has. been. revised.
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. Instead,. phospholipids. such. as. dipalmitoyl. phosphatidyl-
choline. (DPPC). and. TPGS. were. found. to. be. more. effective. emulsiiers. in. nanoparticle.
fabrication.
12,13
.Phospholipids.with.short.and.saturated.chains.showed.higher.eficiency.in.
emulsion.of.polymeric.micro/nanoparticles.of.better.physical/chemical.properties..There.
is. no. signiicant. difference. in. morphology. between. TPGS-. and. PVA-emulsiied. PLGA.
nanoparticles.. However,. TPGS. has. been. found. to. be. able. to. improve. the. drug. encapsu-
lation. eficiency. up. to. 100%,. compared. with. PVA-emulsiied. nanoparticles,. at. only. 59%..
Moreover,.the.amount.of.TPGS.needed.in.the.fabrication.process.was.only.0.015%.(w/w),.
which.was.far.less.than.the.1%.PVA.needed.in.a.similar.process.
14,15
8.2.2 Nanoparticle Fabrication
Nanoparticles.can.be.fabricated.by.various.methods,.such.as.polymerization.or.dispersion.
of. the. preformed. polymers,. solvent. extraction/evaporation. method,. salting-out. method,.
dialysis. method,. supercritical. luid. spray. technique,. and. nanoprecipitation. method..
Solvent.extraction/evaporation.is.used.in.current.research.due.to.its.acceptable.drug.load-
ing.eficiency,.ease.of.processing,.and.good.reproducibility..In.this.review,.we.highlight.the.
most.useful.methods.of.nanoparticle.fabrication:.solvent.extraction/evaporation,.dialysis,.
and.nanoprecipitation.
8.2.2.1 Solvent Extraction/Evaporation Method
The
s
olvent.extraction/evaporation.method.is.the.most.widely.used.technique.for.nano-
particle.fabrication..In.this.technique,.a.selected.polymer.is.irst.dissolved.in.an.organic.
solvent. such. as. dichloromethane,. chloroform,. or. ethyl. acetate.. The. hydrophobic. drug. is.
then.dissolved.in.the.polymer.solution..The.solution.formed.is.dispersed.in.an.aqueous.
