Biomedical Engineering Reference
In-Depth Information
Figure 9.1
Flow chart of the HFDM method for preparing siRNA-loaded
lipid particles.
This method holds promise for future systemic RNAi delivery
due to its ease of preparation and superior stability of end products
[28]. The lipoplexes produced using the HFDM method compare
favourably with the commonly used post-insertion technique,
producing particles of less than 200 nm in size with high siRNA
entrapment efficiency (>90%) and high gene-silencing efficiency
(Table 9.1) [28]. Importantly, in contrast to post-insertion
preparations, particles made by HFDM retained 100% of their gene-
silencing efficiency after storage at room temperature for at least
four months. They exhibit a high degree of stability in serum with
no breakdown nor aggregation after 24 h [45]. When used
in vivo
via intravenous injection, they rapidly distribute to tissues with the
serum concentration dropping to 10% of the initial value within
2 h. The concentration remained steady after 4 h, and the elimination
half-life of our particles was 44 h. This is favourable compared to
SNALPs, which have an elimination half-life of 6.5 h. When used
in
vivo
via intravenous injection, they efficiently accumulate in tumours
and are effective at reducing tumour size when targeting the HPV
E6/E7 gene in cervical cancer models [45]. Our HFDM particles also
Table 9.1
Summary of size, polydispersity index, zeta potential, and
siRNA entrapment efficiency for siRNA-loaded PEGylated lipid
particles formulated using either HFDM or post-insertion
method
HFDM
method
Post-insertion
method
Size (nm)
193.2 ± 10.7
178.9 ± 11.8
siRNA entrapment efficiency (%) 94.7 ± 0.61
89.9 ± 2.66
Polydispersity index
0.32 ± 0.03
0.12 ± 0.06
Zeta potential(mV)
45.1 ± 1.17
41.1 ± 1.51
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