Biomedical Engineering Reference
In-Depth Information
lowering.of.the.environmental.pH,.but.still.PLGA.has.been.used.most.widely.because.of.the.
fact.that.various.formulations.have.been.approved.by.the.Food.and.Drug.Administration.
(FDA).. There. may. be. other. synthetic. polymers. that. may. possess. better. properties. than.
PLGA,.but.if.the.polymers.have.not.been.used.in.formulations.approved.by.FDA,.they.are.
not.the.prime.candidate.for.making.clinical.formulations.
Nano/microparticles.of.PLGA.have.been.prepared.by.different.methods,.such.as.solvent.
extraction.and.evaporation.methods.based.on.the.double.emulsion.approach,.salting-out.
method,. and. nanoprecipitation. method.. Of. these,. double. emulsion. methods. have. been.
used.most.widely..The.solvent.evaporation.method.follows.two.steps..First,.emulsiication.
of.the.polymer.and.drug.in.a.solvent,.such.as.chloroform.and.ethyl.acetate,.followed.by.
solvent.removal.during.which.polymer.precipitates.to.form.particles..Italia.et.al..carried.
out.an.experiment.to.obtain.cyclosporine-loaded.PLGA.nanoparticles.of.around.150.nm.
by.the.emulsion.evaporation.method..Interestingly,.this.nanoparticle.demonstrated.much.
higher.intestinal.uptake.than.commercial.products.(SIM-Neoral).as.well.as.cyclosporine.
suspension.. Because. of. the. eficient. uptake,. bioavailability. of. nanoparticles. was. 19.2%.
higher.than.SIM-Neoral..Surprisingly,.a.cyclosporine-loaded.nanoparticle.system.showed.
longer.pharmacokinetic.proile.after.5.days.as.compared.with.3.days.by.the.control.(Italia.
et.al..2007).
One.of.the.challenges.in.making.nano/microparticles.in.large.quantities.for.commercial.
applications. is. the. dificulty. of. scale-up. production,. especially. particles. with. narrow.
size. distributions.. Emulsion. methods. inherently. result. in. a. wide. size. distribution,. and.
many. times. the. particles. in. the. large. size. portion. have. to. be. removed,. as. they. are. too.
big. for. administration. using. a. needle. commonly. used. for. intravenous. or. subcutaneous.
injection.. Thus,. making. particles. with. a. predeined. size. and. narrow. size. distribution.
has.become.very.important..Recent.advances.in.nanotechnology.have.resulted.in.nano/
microfabrication.methods.of.making.particles.with.a.predeined.size.and.shape..One.such.
approach.is.based.on.the.hydrogel.template.method..Acharya.et.al..presented.a.hydrogel.
template.method.for.making.nano/microparticles.using.gelatin.templates.(Acharya.et.al..
2010)..Gelatin.can.be.manipulated.to.attain.a.speciic.mechanical.strength.and.have.speciic.
size.of.cavities.by.sol-gel.transition.phenomenon..Once.the.cavities.are.illed.with.drug-
containing.PLGA.in.an.organic.solvent,.solid.PLGA.particles.are.obtained.by.removing.the.
solvent,.followed.by.simple.dissolution.of.the.gelatin.template.in.water.(Figure.23.3)..Figure.
23.4.shows.submicron-size.particles.are.prepared.by.using.the.gelatin.template.method.
In.an.alternative.approach,.a.luidic.nanoprecipitation.system.(Figure.23.5).was.used.to.
make.particles.of.homogeneous.sizes..The.instrument.is.composed.of.a.dispersing.chan-
nel.and.inlet.channel.inserts,.which.can.be.situated.in.the.center.of.a.dispersing.vessel..
The.advantage.of.this.system.is.that.they.can.let.the.PLGA.droplets.be.exposed.with.con-
sistent.condition.from.the.inlet.channel,.so.it.is.easy.to.fabricate.particles.of.a.certain.size.
by.adjusting.the.low.rate.in.the.dispersing.channel.(Xie.and.Smith.2010).
23.3
.
Administration of Nanocarriers
23.3.1
.
injectable Nanocarrier Systems
Intravenous. administration. of. nanocarriers. requires. speciic. size. ranges.. Human. blood.
vessels. get. thinner. and. inally. convert. to. a. narrow. capillary. with. a. diameter. of. about.
2.μm..Thus,.particles.of.inappropriate.sizes.can.hinder.blood.low,.if.they.congregate.and.
