Biomedical Engineering Reference
In-Depth Information
Hydrophilic head group
Aqueous phase
Hydrophobic bilayer
Nonionic surfactant
Figure 23.1
(See companion CD for color igure.)
. Structure. of. lipid. nanocapsule. composed. of. an. oily. phase,. aqueous.
phase,.and.nonionic.surfactant.
range,.most.of.the.surfactant.monolayer.is.inclined.to.form.an.O/W.emulsion.with.a.high.
conductivity. value. around. 35.mS/cm.. On. the. other. hand,. it. becomes. more. lipophilic. as.
the.temperature.increases,.so.it.shapes.W/O.emulsion.that.has.a.very.low.conductivity.as.
close.to.0.mS/cm..Based.on.the.PIT.principle,.three.components.existing.as.a.W/O.status.
start.to.form.O/W.emulsion.by.rapid.dilution.in.cold.water..As.the.result.of.lowering.the.
temperature.in.a.short.time.with.an.optimized.ingredients.ratio,.the.particle.size.becomes.
less. than. 100.nm.. Furthermore,. it. is. reported. that. the. repeated. cooling. process. crossing.
the.PIZ.makes.the.LNPs.more.stable.(Anton.et.al..2008;.Huynh.et.al..2009;.Moghimi.and.
Szebeni.2003).
The. lipid. nanocapsules. are. thought. to. be. internalized. into. the. cell. by. employing.
the. endogenous. cholesterol,. which. is. needed. in. both. clathrin-dependent. and. clathrin-
independent.pathways..Studies.have.indicated.that.the.lipid.nanocapsules.of.around.100.nm.
in.size.is.inluenced.by.the.aforementioned.mechanism,.but.lipid.nanocapsules.of.smaller.
sizes.are.inclined.to.employ.the.clathrin-.and.caveolae-independent.pathways.(Figure.23.2).
This. particulate. system. seems. to. inhibit. the. P-glycoprotein. (PGP). function,. which.
is. known. for. an. ATP-dependent. drug. eflux. pump. widely. expressed. in. the. intestinal.
epithelium,. hepatocytes,. renal. proximal. tubular. cells,. and. BBB.. PGP. is. one. of. the. main.
factors.that.pump.out.the.anticancer.agents.from.the.membrane.of.the.cell,.so.this.defense.
system. makes. cancer. cells. more. resistant. to. anticancer. drugs.. The. comparative. study. of.
Taxol.and.paclitaxel-loaded.lipid.nanocapsules.showed.that.the.latter.was.more.effective.
against. 9L. and. F98. cells.. Single. injections. of. paclitaxel-loaded. lipid. nanocapsules. have.
shown.remarkably.reduced.tumor.volume.and.inhibited.tumor.growth.(Coon.et.al..1991;.
Lacoeuille.et.al..2007;.Lamprecht.and.Benoit.2006)..The.feasibility.of.oral.administration.was.
tested.based.on.the.hypothesis.that.overcoming.the.PGP.of.enterocytes.could.enhance.the.
poor.bioavailability.of.anticancer.drugs..The.paclitaxel-loaded.lipid.nanocapsules.resulted.
in.three.times.higher.blood.concentration.as.compared.with.Taxol.(Peltier.et.al..2006).
