Biomedical Engineering Reference
In-Depth Information
34
(Fig. 3.2).
It is also known that having stable brush configuration
(>8 mol% DSPE-PEG 2000) is beneficial in order to avoid RES and
achieve passive targeting.
Passive targeting has been successfully used as an approach
to maximize passive delivery, specifically the EPR effect, which is
passive delivery to tumors. However, increasing passive delivery
by altering vessel permeability or PEGylation may increase the
risk of off-target effects and immune response due to its prolonged
systemic circulation.
Therefore, an alternative approach for the
targeted delivery of NPs has been directed toward the specific
receptors or antigens expressed on the surface of tissue/tumor
endothelium or tumor cells, which is also referred to as active
targeting.
84
84
There have been extensive studies on tumor targeting
using various tumor-specific or organ-specific ligands, such as
anisamide or GC4 scFv, conjugated to NPs.
86
The effects of applying
active targeting on NPs will be discussed later. Examples of successful
nanocarriers are the membrane/core NPs developed in our lab. The
following is a summary of these NPs.
3.4.1
LPD
The first developed membrane/core type NP was LPD, which is a self-
assembled non-viral nanoparticle (NP) formulation for a systemic
delivery of nucleic acid.
3.4.1.1
Formulation of LPD
LPD NPs are composed of nucleic acid (DNA and/or RNA), a
polycationic macromolecule, and cationic liposomes. Both LPD
and PEGylated LPD NPs have been prepared by combining cationic
liposomes and polycation condensed nucleic acid. In general,
the formation of NPs with nucleic acid has been done through a
self-assembling process mediated mainly by the charge-charge
interaction, where cationic carriers bind with anionic nucleic acid.
It is known that the
transfection efficiency with the cationic
lipid, DOTAP, can be improved by incorporating cholesterol into
the formulation.
in vivo
87-89
The liposome containing cholesterol tends to
attract less protein and further reduces the liposomal uptake by the
RES.
90
91
demonstrated that less than 1% of cells were
transfected with DOTAP in the presence of 50% and 100% serum,
Crook
et al.
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