Biomedical Engineering Reference
In-Depth Information
Liposomes.that.destabilize.as.a.consequence.of.an.acid.trigger.phase.transition.induced.
on.an.attached.polymer.such.as.poly(NIPA).and.PG.possess.a.complex.architecture..In.the-
ory,.the.destabilization.pH.can.be.tuned.by.the.percentage.and.degree.of.hydrophilicity.of.
carboxilic.acids.added.as.comonomers.or.linked.to.the.polymer.backbone..Remarkably,.the.
pegylation.does.not.reduce.the.pH.sensitivity.in.plasma.of.liposomes.bearing.poly(NIPA-
co-MAA-co-DODA)..Their.performance.in.vivo.remains.unknown..Probably.the.shorter.
the. poly(NIPA). chains,. the. more. biodegradable. and. biocompatible. the. polymer. will. be..
However,. multiple. dosages. of. liposomes. bearing. poly(NIPA). and. PG. polymers. deserve.
special.attention,.in.view.of.the.previous.experience.with.pegylated.liposomal.doxorubi-
cin.that.caused.severe.toxic.reactions.due.to.the.accelerated.blood.clearance.effect.
Clearly,.the.major.ield.of.preclinical.application.of.pH-sensitive.liposomes.is.represented.
by.those.targets.that.are.not.achieved.upon.long.circulation.and.accumulation.at.EPR.effect.
sites..DOPE/CHEMS.pH-sensitive.liposomes.can.be.easily.prepared,.employing.commer-
cially.available.components..Though.the.scale-up.feasibility,.sterilization,.and.shelf.life.of.
these.formulations.remain.to.be.determined,.their.biocompatibility.at.multiple.dosages.is.
well.known.and.positions.them.as.potential.candidates.to.enter.clinical.studies..In.sum,.
the.equation.of.drawbacks.of.simplicity.vs..advantages.of.complexity.will.be.solved.when.
in.vivo.performance,.biocompatibility,.and.scale-up.feasibility.are.determined.
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