Biomedical Engineering Reference
In-Depth Information
nonpolar.region.is.oriented.away.from.the.aqueous.phase..Liposomes.are.biocompatible,.
mask.the.toxicity.of.the.drug,.and.increase.its.time.in.the.circulation,.and.thus.the.eficacy..
Since. their. discovery,. a. number. of. them. have. been. tested. in. clinical. trials,. and. some. of.
them.were.approved.by.the.U.S..Food.and.Drug.Administration.(FDA).
The.properties.of.liposomes.(i.e.,.size,.charge,.release.kinetics,.etc.).depend.on.their.for-
mulation. and. the. preparation. methods.. The. spontaneous. (and. uncontrolled). formation.
of.liposomes.leads.to.a.population.of.vesicles.ranging.from.10.nm.to.10.µm.in.diameter..
Liposomes.can.entrap.hydrophilic.and.hydrophobic.molecules.in.their.aqueous.compart-
ment.and.within.their.membrane,.respectively..One.has.to.consider.the.phase.transition.
temperature,.chain.length,.and.degree.of.saturation.of.the.phospholipids,.and.the.perme-
ability.of.the.vesicles.toward.various.compounds..Although.liposomes.are.formed.spon-
taneously,.there.are.several.methods.to.control.their.properties.and.obtain.a.population.
with.predetermined.features.
Liposomes.can.be.designed.to.be.neutral.or.charged..The.major.constituents.of.neutral.
liposomes. are. uncharged. phosphatidyl. cholines. (PCs). such. as. dipalmitoyl. phosphatidyl.
glycerol.(DPPG),.dipalmitoyl.phosphatidyl.choline.(DPPC),.and.cholesterol..Phosphatidyl.
ethanolamine. (PE). is. used. for. positively. and. dipalmitoyl. phosphatidic. acid. (DPPA). for.
negatively.charged.liposomes..Sterols,.and.especially.cholesterol,.are.very.important.for.
liposome. stability.. They. themselves. cannot. form. the. bilayer. structures,. but. they. can. be.
incorporated. into. the. liposomes. up. to. 1:1. molar. ratio.. Cholesterol. presence. in. the. lipid.
bilayer.has.a.signiicant.effect.on.the.phase.transition.temperature..As.the.concentration.
of. cholesterol. in. the. bilayer. membrane. increases,. the. phase. transition. temperature. also.
increases,. up. to. a. certain. degree.. This. indicates. that. cholesterol. incorporation. increases.
the.stability.(and.rigidity).of.the.bilayer..In.addition,.permeability.and.luidity.of.the.mem-
brane.are.also.affected.by.cholesterol.
Liposomes.are.classiied.according.to.the.number.of.bilayers.and.size.(Figure 11.1):
•. Small. unilamellar. vesicles. (SUVs):. Their. diameters. are. generally. in. the. range. of.
20-100.nm,.and.they.have.a.single.bilayer.(Figure 11.1A).
•. Multilamellar.vesicles.(MLVs):.They.are.generally.larger.than.500.nm.in.diameter.
and.have.multiple.bilayers.(Figure 11.1B).
•. Large. unilamellar. vesicles. (LUVs):. Liposomes. of. a. single. bilayer. larger. than.
1,000 nm.in.diameter.are.classiied.as.large.unilamellar.vesicles.(Figure 11.1C).
•. Multivesicular.vesicles.(MVVs):.They.consist.of.several.vesicles.within.one.large.
common.liposome..They.are.generally.larger.than.1000.nm.(Figure 11.1D).
A
B
Small unilamellar vesicles
(SUVs) (20-100 nm)
Multilamellar vesicles
(MLV) (>500 nm)
C
D
Large unilamellar vesicles
(LUVs) (>1000 nm)
Multivesicular vesicles
(MVV) (>1000 nm)
FIGURE 11.1
Classiication.of.liposomes.according.to.their.size.and.bilayer.number.
