Biomedical Engineering Reference
In-Depth Information
to. have. unique. and. superior. properties. than. a. microsized. drug. carrier.. An. active. agent.
can.be.incorporated.into.nanoparticles.by.a.variety.of.means.ranging.from.simple.mixing.
to.covalent.grafting.(Bawa.et.al..2005;.Gelperina.et.al..2005)..Technically,.nanosized.drug.
carriers. can. signiicantly. improve. formulation. design,. biodistribution,. and. bioavailabil-
ity.through.eficient.delivery.into.the.desired.target.site,.reducing.unwanted.side.effects.
(Dubin.2004)..Abraxane,.one.of.the.clinical.products.available.in.2005,.is.a.good.example.
demonstrating.the.use.of.a.benign.carrier,.as.compared.with.Cremophor
®
.EL,.in.delivering.
paclitaxel.to.the.tumor.site.(Vishnu.and.Roy.2011)..Another.promising.application.area.of.
nanocarrier.is.to.make.the.drug.delivery.system.small.enough.to.penetrate.the.blood.brain.
barrier.(BBB).and.reach.the.lesion.in.the.brain.for.treating.various.diseases.(Devalapally.
et.al..2007;.Rathbun.et.al..2006;.Sosnik.et.al..2010).
This. chapter. describes. improved. eficacy. of. nanoparticulate. drug. delivery. systems. as.
compared. with. microsized. drug. delivery. systems,. current. fabrication. methods,. and. the.
prospective.possibility.of.developing.commercial.products.that.can.beneit.patients.
23.2
.
Nanotechnology-Based Drug Delivery Systems
23.2.1
.
Nanocrystals
One. of. the. main. physicochemical. properties. of. a. drug. for. successful. development. into.
clinical.application.is.the.water.solubility..In.many.cases,.the.drug.solubility.in.water.is.
not.high.enough.to.lead.to.in.vivo.therapeutic.eficacy..Many.promising.drugs.have.been.
abandoned.due.to.their.poor.water.solubility..More.than.half.of.all.the.newly.developed.
drugs.are.known.to.have.poor.water.solubility..Poor.water.solubility.requires.use.of.higher.
amount.of.the.drug,.and.this.in.turn.may.result.in.higher.incidents.of.side.effects.(Speiser.
1998)..For.this.reason,.poorly.soluble.drugs.have.been.formulated.by.a.variety.of.different.
approaches,. ranging. from. simple. salt. formation. to. complicated. drug. delivery. systems.
such. as. polymer. micelles.. Of. these,. the. nanocrystal. approach. has. received. signiicant.
attention..Drug.nanocrystals.dissolve.faster.than.their.microsized.drug.counterparts.due.
to.substantially.increased.surface.area.(Junghanns.and.Müller.2008)..Several.nanocrystal.
formulations. have. become. clinically. available.. Sirolimus,. an. immunosuppressant,. is. a.
poorly.water-soluble.drug,.and.it.was.available.as.an.oral.solution.and.tablet.(Rapamune
®
,.
Pizer)..When.it.was.made.into.a.formulation.of.nanocrystals.less.than.200.nm.(Rapamune),.
the. solid. oral. formulation. was. equally. effective. as. the. solution. formulation. (Merisko-
Liversidge. et. al.. 1996).. Rapamune. is. a. product. generated. by. NanoCrystal
®
. technology.
from. Elan. Pharmaceuticals.. Another. three. examples. of. the. NanoCrystal. technology. are.
Megace.ES
®
.(megestrol.acetate,.Par.Pharm.Co.),.Tricor
®
.(fenoibrate,.Abbott),.and.Emend
®
.
(aprepitant,.Merk).(Adis.2007;.Deschamps.et.al..2009).
Nanocrystals.can.be.fabricated.by.several.methods..The.precipitation.method.uses.the.
principle. in. which. the. drug. that. has. different. solubilities. to. various. solvents. can. have.
the. possibility. to. create. a. drug. nanocrystal.. The. drug. in. a. solvent. is. directly. added. to.
another. solvent. that. the. drug. is. hardly. or. not. dissolved. into.. Hydrophobic. compounds.
such. as. DiO. and. perylene. used. for. photodynamic. therapy. and. image,. for. example,. are.
dissolved. in. acetone,. then. the. acetone. solution. is. quickly. injected. into. water. with. a.
microsyringe. to. rapidly. form. drug. precipitates.. Another. interesting. method,. known. as.
Nanomorph.developed.by.Soliqus/Abbott,.is.to.precipitate.the.nanosized.drug.particles.in.
an.amorphous.form.to.drastically.enhance.the.drug.dissolution.rate..Generally,.amorphous.
