Biomedical Engineering Reference
In-Depth Information
or.without.EGFR.vs..~1%.for.free.drug.or.pH-insensitive.liposomes..The.authors.claim.that.
pegylated.targeted.pH-sensitive.liposomes.retain.the.pH.sensitivity.
Administered.on.non-small-cell.lung.cancer.in.a.nude.mice.model
152
.at.160.mg.GEM/
kg.(8.i.v..doses,.days.0,.3,.6,.10,.13,.16,.20,.and.28),.these.liposomes.diminish.the.growth.of.
tumor.(20-2.26.folds.volume.reduction.after.1.month),.improving.the.performance.of.the.
nontargeted.pH-sensitive.liposomes.and.the.free.drug..The.cell.proliferation.was.reduced.
in.direct.relation.with.the.increased.apoptotic.index.
20.7.3 Scintigraphic Diagnostic
A. particular. application. as. diagnostic. radiopharmaceuticals. has. been. recently. pub-
lished,.where.the.biodistribution.and.ability.of.pegylated.pH-sensitive.liposomes.(DOPE/
CHEMS/PE-Peg,. 6.5:3.0:0.5). were. radiolabeled. with.
99m
Tc-hexamethylpropylene. amine.
oxime.(
99m
Tc-HMPAO).to.identify.inlammatory.regions.in.a.rat.focal.inlammation.model.
upon.i.v..administration.
153
.For.identiication.of.an.inlammation.region,.the.target-to-no.
target.ratio.must.be.at.least.2,.allowing.for.the.acquisition.of.improved.scintigraphic.imag-
ing. quality..
99m
Tc-stealth. pH-sensitive. liposomes. offer. a. high. target-to-no. target. ratio. at.
earlier. times. than. other. pH-insensitive. liposomes.. It. was. possible. to. detect. 0.43%. of. the.
injected.dose/g.at.only.30.min.postinjection.of.
99m
Tc-pegylated.pH-sensitive.liposomes..In.
contrast,.the.same.uptake.level.was.obtained.using.nonpegylated.and.pH-insensitive.lipo-
somes,.composed.of.DSPC,.DMPG,.and.Chol,.24.h.after.injection,
154
.while.using.pegylated.
pH-insensitive.liposomes.resulted.in.the.same.absolute.uptake.at.only.2.h.after.adminis-
tration.
155
.The.value.of.the.inlammatory.and.noninlammatory.site.radioactivity.counting.
ratio.was.greater.than 5.at.2.h.postadministration.
20.8 PreclinicalApplicationsofpH-SensitiveLiposomes
Long.circulating.liposomes.extravasate.at.the.sites.of.existing.enhanced.permeability.and.
retention.(EPR).effect.and.justify.the.need.for.absence.of.early.drug.leakage.and.aggrega-
tion..However,.there.are.many.therapeutic.targets.other.than.EPR.sites..Examples.are.dis-
eases.affecting.cells.that.are.accesible.from.blood.circulation,.such.as.those.from.the.RES,.
like.Kupffer.cells.and.hepatocytes.in.the.liver,.or.spleen.and.bone.marrow.macrophages..
To.target.these.cells,.nonpegylated.pH-sensitive.liposomes.are.suitable.vehicles,.and.long.
circulation.is.not.essential..In.particular,.nonpegylated.pH-sensitive.liposomes.adminis-
tered.to.the.skin.have.shown.promising.results.in.therapeutics.of.melanoma,.and.also.in.
targeting.skin.antigen-presenting.cells.(Langerhans.and.dendritic.cells).to.elicit.immune.
local.responses..The.complexation.of.nonpegylated.pH-sensitive.liposomes.with.cationic.
lipoplexes.was.successfully.applied.to.in.vivo.gene.therapy..In.the.following.section,.the.
latest.preclinical.application.of.nonpegylated.pH-sensitive.liposomes.will.be.discussed.
20.8.1 Chagas Disease
Chagas.disease.is.caused.by.the.parasite.
Trypanosoma cruzi
..In.humans,.
T. cruzi
colonizes.
cells.of.the.RES,.and.also.cardiac.and.nerve.cells..Parasites.can.be.found.as.trypomastig-
otes,.an.infective.extracellular.circulating.form.that.predominates.in.the.acute.clinical.form,.
or.as.intracellular.cytoplasmic.amastigotes,.which.predominate.in.the.indeterminate.and.
