Biomedical Engineering Reference
In-Depth Information
Clathrin-independent endocytosis
Clathrin-dependent endocytosis
LNP
LNP
Lecithin
Nonionic surfactant
Late endosome
Recycling
endosome
Drug
Triglyceride
Golgi
Lysosome
Figure 23.2
(See companion CD for color igure.)
.Schematic.representation.of.endocytosis.mechanisms.of.lipid.nanopar-
ticle.prepared.by.phase-inversion.method.
Lipid. nanocapsules. have. several. beneicial. properties. for. making. them. a. good. drug.
delivery.vehicle.for.increased.bioavailability..They.include.small.particle.size,.narrow.size.
distribution,. high. loading. eficiency. of. lipophilic. drugs,. long-term. stability,. and. higher.
chances.of.rapid.cellular.internalization.with.longer.residence.time.
23.2.5
.
PLgA Particles
For. long-term. delivery,. ranging. from. weeks. to. months,. drugs. need. to. be. incorporated.
into.slowly.biodegradable.nanoparticles.or.microparticles..Since.it.is.very.inconvenient.to.
remove.the.drug.delivery.system.after.the.drug.delivery.is.over,.biodegradable.polymers.
are. usually. used. in. long-term. drug. delivery. systems.. There. are. various. biodegradable.
polymers,.such.as.polyorthoesters,.polyesters,.polyphosphazenes,.and.polyalkylcyanoac-
rylates,. which. have. labile. linkages. that. can. make. the. polymer. decompose. under. physi-
ological. conditions.. Synthetic. polymers. have. many. beneits. over. natural. biodegradable.
polymer.systems..Synthetic.polymers.can.be.produced.with.controllable.properties.at.high.
purity.in.large.quantities,.and.they.are.usually.free.from.immune.responses.by.the.body.
Of. the. many. synthetic. polymers,. polymers. made. of. lactic. and. glycolic. acids. are. most.
widely.used..Poly(lactic-co-glycolic.acid).(PLGA).breaks.down.into.lactic.acid.and.glycolic.
acid,. natural. components. of. the. body.. Many. formulations. made. of. PLGA. have. been.
administered.to.the.body.through.intravenous,.subcutaneous,.and.intramuscular.routes..
The. ester. linkage. of. PLGA. goes. through. random. cleavage. to. produce. carboxylic. acid.
and. hydroxyl. groups.. The. generated. carboxyl. group. lowers. the. pH. of. the. environment,.
resulting.in.autoacceleration.of.the.hydrolysis.process..The.degradation.time.depends.on.
polymer.properties,.such.as.molecular.weight,.glass.transition.temperature,.crystal.form.
of. the. polymer,. and. the. molar. ratio. of. the. lactic. acid. and. glycolic. acid. (Gopferich. 1996;.
vonBurkersroda. et. al.. 1997).. Sometimes. PLGA. polymers. cause. inlammation. due. to. the.