Biomedical Engineering Reference
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approximately 5 mg/ml polymer and 0.5 mg/ml siRNA, respectively).
However, for the polyamine-modified HA variants such as HA-
spermine, HA-PLL and HA-PEI systems, the best polymer:siRNA
mass ratio was found to be much lower at 54:1 (at 3 mg/ml of polymer
and 0.5 mg/ml of siRNA, respectively) [19].
Interestingly, in this class of polymers, except for HA-SP, which needed
a lower pH (approximately 5.0-5.5) environment for encapsulation,
we could achieve 100% siRNA encapsulation efficiencies even
at neutral pH, which could be attributed to the self-condensing
ability of the charged PEI/PLL units as reported elsewhere. Another
interesting observation was that the HA-PEI/siRNA prepared in 1X
PBS (pH=7.4) were found to be smaller in size (of the order of 50-
60 nm) when compared to the ones made using water as the solvent
(size approximately 150-200 nm) (
Table 3.1
). This may probably be
due to tighter binding between the siRNA and the HA-PEI polymer
due to the buffering of counter ions and a shift in charge balance
in 1X PBS resulting in the formation of smaller size particles. Also,
these HA-PEI/siRNA nanoparticles surprisingly exhibited negative
surface charge despite the presence of positively-charged PEI. These
results were thought to reflect a positive 'core' containing the PEI/
PLL that holds the intact siRNA, while displaying a hydrophilic 'shell'
of negatively-charged HA (
Figure 3.3
). The proposed mechanism is
similar to the ones reported by Jiang and co-workers [21]. Although
their systems had high PEI content compared to HA and differed
from the ones we synthesised with much higher HA content, the
mechanism of self-assembly remains identical.
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