Biomedical Engineering Reference
In-Depth Information
d
n
4
y
3
n
g
|
3
Scheme 4.12
Synthesis of (A) pluronic (P85) amine and (B) P85-b-P[Asp(DET)]
copolymers.
liposome for pulmonary gene transfection using 6-lauroxyhexyl lysinate
(LHLN).
104
When administered by intratracheal instillation into rat lungs for
in vivo evaluation, LHLN-liposome/DNA complexes exhibited higher pulmo-
nary gene transfection efficiency than Lipofectamine 2000/DNA complexes.
Hu et al. developed pegylated immuno-lipopolyplex (PILP) gene delivery
systems by employing PEI/DNA complexes, as well as anionic liposomes
composed of POPC, (DSPE)-PEG2000, and (DSPE)-PEG2000-biotin, and by
using streptavidin-monoclonal antibody conjugating through the biotin group
located at the distal end of the PEG spacer as the targeting antibody.
105
These
complexes showed high efficiency in gene delivery to liver cancer cells but with
no significant cytotoxicity. Intravenous administration of the PILP resulted in
tumor- and liver-targeted gene expression of the reporter genes EGFP and
luciferase, as opposed to the lung-targeted gene expression obtained with PEI/
DNA complexes, causing no cytokine production and liver injury. PILP are
promising gene delivery systems which may be used to target liver cancer.
Shirazi et al. have presented the efficient synthesis of a series of degradable
multivalent cationic lipids (CMVL
n
, n 5 2-5) containing a disulfide bond
spacer between the headgroup and lipophilic tails (Scheme 4.13).
106
This
spacer is designed to be cleaved in the reducing milieu of the cytoplasm and
thus decrease lipid toxicity. The CMVLs (n 5 3-5) exhibit reduced cytotoxicity
and transfect mammalian cells with efficiencies comparable to those of highly
efficient nondegradable analogs and benchmark commercial reagents such as
Lipofectamine 2000.
Huang et al. have synthesized two novel protonated cyclen and imidazolium
salt-based cationic lipids, which differ only in their hydrophobic region
(cholesterol or diosgenin).
107
Cationic liposomes were easily prepared from
each of these lipids individually or from the mixtures of each cationic lipid and
