Biomedical Engineering Reference
In-Depth Information
NegativelyCharged
PositivelyCharged
+
+
siRNA
CalfthymusDNA
(High Moleclar Weight )
Protamine
(HighMoleclar Weight)
Liposomes
(DOTAP/cholesterol=
1/1)
100Ͳ120nm,
20mV
DSPEͲPEGor
DSPEͲPEGͲAAmicelle
Figure 3.3
The outline for the preparation of LPD NPs.
3.4.1.2 The ef fect of surface modification of LPD
3.4.1.2.1
Passive targeting: efficient PEGylation
In general, the degree of modification with PEG is usually found to
be less than 5 mol% if the liposome is to maintain the integrity of
the lipid membrane, due to the detergent-like activity of PEG.
85, 96
LPD NPs, however, show a relatively high mol% (~10.6 mol%) of
PEG arranged in the brush mode and still remain intact. The key to
tolerating the high mol% of PEG arranged in the brush mode may
be the presence of two separate lipid bilayers, a unique feature of
LPD. The inner layer is supported and stabilized by the charge-
charge interaction of the cationic lipids with the negatively charged
core. The neutral charge of LPD particles supports the complete
shielding provided by the high density of PEG in the brush mode.
And these stealthy LPD NPs exhibit a reduced liver uptake in the
isolated and perfused liver model (12 ± 5.7% ID at 4 h) and deliver
siRNA efficiently into tumor (~30% ID at 4 h).
81
These results
indicate that PEGylation plays an important role in preventing
serum opsonization and in abolishing the non-specific RES uptake.
Since the main loss of the injected NPs by RES comes from the
liver and spleen, the low RES uptake of LPD might efficiently help
the NPs to reach the tumor with an enhanced permeability and
retention (EPR) effect.97
97
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