Biomedical Engineering Reference
In-Depth Information
3.4.2.1
Physicochemical characteristic of LCP
An amphiphilic phospholipid, DOPA, plays an important role
in the preparation of LCP NPs. Because of the presence of a
phosphate group, it is proposed that DOPA participates in the
CaP precipitate formation at the interface.
The resulting DOPA-
coated CaP core is hydrophobic and soluble in organic solvent. This
insolubility of the NPs allows a convenient washing of the cores in
ethanol to remove excess surfactants such as free DOPA. The size
of the final LCP formulation is approximately 40 nm, much smaller
than that of LPD (120-150 nm).
152
Since the CaP cores have a hollow
structure, it is possible to entrap partially or completely water soluble
drugs for a targeted delivery.
80
151
The hydrophobic core, coated with
DOPA, provides a wide range of selection for the outer leaflet lipid
in the bilayer surface. Both neutral, e.g., DOPC, and cationic lipid,
e.g., DOTAP, may be used as the outer leaflet lipid stabilized by
cholesterol.
By comparing the zeta potentials of both pure liposomes and
LCP particles using different lipids for the outer leaflet, it was
determined that the surface of the NPs is determined mainly by the
outer leaflet lipid, not by the inner leaflet lipid, DOPA. The salient
features of the LCP particles include the CaP core, in which nucleic
acid cargo is encapsulated, and an asymmetrical lipid bilayer coat.
Like LPD, the surface lipid bilayer is a supported bilayer that allows
the insertion of a large amount of DSPE-PEG with or without a
tethered targeting ligand. Two to three fold higher PEG density was
required to enhance the tumor uptake of LCP than the corresponding
LPD. This is due to the high surface curvature of the LCP compared
with that of the LPD.
3.4.2.2
Potential therapeutic effect of LCP
The rapid dissolution of CaP at acidic pH conditions is the main
reason for the replacement of protamine-DNA core with CaP to
facilitate an enhanced release efficiency of the target cargo. From
the study of the siRNA delivery efficiency of LCP in H460 cells
in vitro
of LCP (5 nM) was 40 times lower than that of LPD
(200 nM), indicating that LCP was more effective in siRNA
delivery than the LPD with no CaP core. The IC
, IC
50
for LCP was
5 nM regardless of the outer leaflet lipid, DOPC or DOTAP, which
suggests that the endosome destabilization effect depended on the
50
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