Biomedical Engineering Reference
In-Depth Information
dynamics. of. the. ensemble,. are. expected. to. follow. thermodynamic. phase-change. and.
phase-equilibria-like. behaviors,. rather. than. simple. aggregation. dynamics,. resulting. in.
discrete.shifts.and.population.equilibria.between.different.sizes.and.structures.
Polymeric.micelles.have.been.reported.for.use.as.drug.solubilization.and.drug.delivery.
agents.because.of.potential.properties.of.sustained,.controlled.drug.release.and.enhanced.
circulating.half-lives.of.the.polymeric.micelles.
16-18
.Work.on.speciic.targeting.of.drugs.and.
encapsulated.active.pharmaceutical.ingredient.(API).has.also.been.performed..However,.
most.of.the.work. involved. attachment.of.a.single. targeting.moiety. at.either. one.or.both.
ends.of.the.polymeric.chain,.resulting.in.very.low.densities.of.the.targeting.moieties.on.
the.polymeric.micelle.surface.
Herein. we. show. that. the. NanoViricides. nanoscopic. polymeric. micelle. technology.
serves.as.a.therapeutic.agent.technology.and.not.simply.as.a.drug.delivery.technology..
In.addition.to.developing.T-.and.π-type.polymeric.chain.structures,.we.have.also.incor-
porated. chemical. functionally. available. groups. within. the. monomer. itself.. We. attach.
targeting.moieties.at.these.functional.points..This.enables.a.signiicantly.larger.density.
of.targeting.moieties.(one.or.two.per.monomer,.as.opposed.to.one.or.two.per.polymeric.
chain),. with. greatly. enhanced. eficiency. of. targeting.. In. fact,. in. the. irst. generation. of.
NanoViricides. technology,. which. we. are. working. on. at. present,. we. have. not. used. the.
feature. of. encapsulating. any. APIs.. We. plan. to. utilize. this. additional. feature. in. future.
generations. of. nanoviricides. to. tackle. viruses. that. cannot. be. controlled. by. our. current.
approach.alone.
7.2 WhatIsaNanoviricide?
When. virus-speciic. ligands. are. chemically. attached. to. a. proprietary. lexible. polymer.
structure.that.mimics.a.biological.cell.membrane,.a.nanoviricide
®
.is.created..Our.lexible.
polymer.backbone.is.comprised.of.a.polyethylene.glycol.(PEG).chain.and.alkyl.pendants..
PEG.forms.the.hydrophilic.shell.and.imparts.nonimmunogenicity;.PEGylation.is.a.famil-
iar.technique.to.minimize.immunogenicity.of.proteins.and.antibodies..The.alkyl.chains.
loat.together.to.make.a.lexible.core,.like.an.immobilized.oil.droplet..The.resulting.mate-
rials.are.polymeric.surfactants.that.form.stable.micelles,.rather.than.liposomes.that.form.
dynamic.micelles..Thus,.these.nanoviricide.micelles.are.freely.soluble.and.conformation-
ally.lexible.in.bodily.luids..Chemical.groups.uniformly.distributed.along.the.polymer.
chain. allow. attachment. of. virus-speciic. ligands. such. as. chemical. moieties,. peptides,.
antibody.fragments,.or.other.proteins..On.irst.contact.with.a.virus.particle,.a.nanoviri-
cide.micelle.may.bind.to.a.virus.particle.because.of.speciic.interaction.between.a.ligand.
attached.to.the.nanoviricide.and.the.glycoproteins.on.the.virus.surface..This.may.cause.
the. lexible. nanoviricide. to. reach. very. close. to. the. virus. surface,. leading. to. additional.
ligands.binding.to.additional.viral.coat.proteins,.in.a.mode.called.cooperative.binding..
Cooperative. binding. is. a. well-known. natural. process. that. forms. the. basis. of. biological.
recognition,.such.as.antibody-antigen.binding.complexes,.DNA.hybridization,.and.pro-
tein. assembly,. among. others.. The. attachment. of. multiple. ligands. to. a. single-polymer.
chain,.coupled.with.the.fact.that.multiple-polymer.chains.make.up.a.single.micelle,.leads.
to.a.very.high.avidity.for.the.resulting.micelle.binding.to.the.virus..This.is.analogous.to.
