Biomedical Engineering Reference
In-Depth Information
therapeutics.and.their.mechanisms.of.action;.it.is.not.meant.to.be.exhaustive.but.simply.
to. provide. examples.. Most. of. the. current. antiviral. strategies. are. based. on. inhibition. or.
modulation.of.the.intracellular.biochemical.pathways,.mediated.by.both.viral.and.host.
cell.enzymes.for.the.production.of.new.virus.particles..For.example,.in.the.case.of.HIV,.
(1).HIV.binds.to.speciic.cell.surface.receptors.that.are.required.for.viral.entry.into.the.
cell,.(2).the.viral.genomic.RNA.(v-RNA).is.copied.into.a.complementary.DNA.molecule.
(v-cDNA). by. the. viral. reverse. transcriptase. (v-RT),. (3). an. enzyme. called. integrase. (v-I).
inserts.copies.of.the.v-cDNA.into.the.nuclear.DNA.of.the.cell,.(4).this.DNA.is.copied.by.
the.cell.machinery.to.make.viral.messenger.RNA.(v-mRNA),.and.is.also.copied.to.make.
new.viral.genomic.RNA.(v-RNA),.(5).the.v-mRNAs.are.then.translated.by.the.cell.to.make.
viral. precursor. proteins,. (6). the. precursor. proteins. are. processed. by. the. viral. protease.
(v-P).to.form.mature.viral.proteins,.and.(7).the.resulting.mature.viral.proteins.and.two.
copies.of.the.newly.made.viral.genomic.RNA.self-assemble,.possibly.with.assistance.from.
both.viral-encoded.and.host.machinery.factors,.such.as.molecular.chaperones,.into.new.
virus.particles.and.are.released.from.the.cell.by.budding. 15
This.chapter.introduces.the.novel.NanoViricides.nanotechnology.that.possesses.potent.
antiviral.eficacy.by.targeting.the.mechanisms.of.cell.attachment.or.cell.binding.of.viruses..
NanoViricides. utilizes. the. technology. of. proprietary. self-assembling. amphiphilic. poly-
mers. that. form. nanoscopic. polymeric. micelles. that. can. blunt. viruses. through. multiple.
mechanisms..Moreover,.they.have.the.potential.to.prevent.the.development.of.drug-resis-
tant.mutants..Polymeric.micelles.are.amphiphilic.polymers.that.contain.hydrophilic.and.
hydrophobic.components,.so-called.block.copolymers,.allowing.self-assembly.into.a.vari-
ety.of.structures.depending.on.the.surrounding.solvent..In.aqueous.environments,.the.
hydrophobic.components.have.a.tendency.to.self-assemble.in.order.to.avoid.contact.with.
water,.while.the.hydrophilic.components.form.a.hydrated.shell;.the.result.is.a.thermody-
namically.stable.structure..This.hydrophilic.deformable.shell.is.exposed.to.the.aqueous.
environment,.while.a.substantially.hydrophobic.core.or.interior.that.may.be.shallow.or.
deep.allows.for.encapsulation.of.guest.molecules..Alternating.polymeric.micelles.contain.
alternating.hydrophilic.and.hydrophobic.segments,.resulting.in.a.very.regular.structure.
that. leads. to. uniform. properties.. In. contrast,. we. have. developed. “pendant”. polymeric.
micelles.. In. these,. the. hydrophobic. segments. are. attached. into. a. monomer. repeat. unit.
as. pendants. or. “tails,”. while. the. pendant-free. polymer. structure. is. hydrophilic. or.
amphiphilic.in.nature.by.itself..By.virtue.of.the.free.ends,.the.tails.self-assemble.in.more.
stable.thermodynamic.conformations.and.enable.a.truly.hydrophobic.core/hydrophilic.
shell.type.of.structure.in.an.aqueous.milieu,.as.opposed.to.alternating.block.copolymers.
containing.hydrophobic.and.hydrophilic.segments.(series.or.S-type.polymeric.micelles)..
We.have.worked.on.T-type.polymeric.micelles,.wherein.there.is.a.single.tail.per.repeat.
unit,.and.later.developed.and.switched.over.to.π-type.polymeric.micelles.possessing.two.
tails. per. repeat. unit,. resembling. a. diacyl-glycerol-like. motif. of. the. biological. cell. mem-
brane.. The. polymeric. micelles. formed. from. these. π-polymers. are. therefore. capable. of.
forming.structures.similar.to.the.biological.membrane..Rather.than.parallel.assemblies.
forming.a.biological.bilayer.lipid.membrane,.a.single-polymer.chain.of.a.T-type.or.π-type.
polymer.would.form.a.single.layer,.globular.micelle.with.a.hydrophobic.core.at.a.limit-
ing.low.concentration.of.the.polymer..At.higher.concentrations,.multiple-polymer.chains.
aggregate.together.to.form.a.larger.globular.stable.micelle,.which.can.range.from.a.few.
nanometers.to.a.few.hundred.nanometers.in.size..At.even.higher.concentrations,.liquid.
crystalline. assemblies. resembling. biological. membranes. may. occur.. Because. of. the. sig-
niicant.energy.differences.relecting.addition.of.a.single-pendant.polymeric.chain.to.an.
existing.assembly,.the.distribution.of.particle.sizes.of.the.ensemble,.as.well.as.structural.
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