Biomedical Engineering Reference
In-Depth Information
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by drug-loaded NPs.
The hepatic uptake was reversibly blocked
by this method but not the splenic uptake. Recent strategies focus
mostly on the modification of properties of NPs using hydrophilic
polymers to sterically shield the hydrophobic surface of NPs and to
avoid interaction with opsonins and/or phagocytic cells of the RES.
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PEG, a hydrophilic and inert polymer, has been widely used as a steric
barrier on the surface of NPs, which minimizes protein binding,
leading to prolonged circulation with improved pharmacokinetic
properties.
Figure 3.2
PEG conformation on liposome surface.
There are two methods for grafting PEG onto the surface of
liposomes. The first one, hydrating a lipid film consisting of both
PEG-phospholipids and other lipid components at the same time,
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allows the PEG to extend from the lipid bilayer to both the inner
aqueous core and the outer aqueous phase. The other method, called
post-insertion, has been commonly used when PEG-phospholipids
are incorporated with pre-formed liposomes
by hydrophobic
interactions with the acyl chains of liposomal lipids, and permits
only the outer surface of liposomes to be modified. In order to avoid
opsonization efficiently, it is important that the surface of NPs is
sufficiently and stably covered by PEG. The brush model has been
known to be the ideal configuration to achieve complete coverage
of the surface of the NPs. Theoretically, for a 100 nm liposomal
particle modified with DSPE-PEG 2000, there are three possible
configurations depending on the mol%: the mushroom conformation
with <4 mol% DSPE-PEG 2000; the transition configuration with
4-8 mol%; and the brush mode with >8 mol% modification
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