Biomedical Engineering Reference
In-Depth Information
and doxorubicin. This is the LPD-II (anionic liposome-polycation-
DNA) formulation discussed below.
3.4.1.4.2
LPD-II
In order to increase the entrapment efficiency of doxorubicin in
LPD NPs, LPD-II containing anionic liposome instead of cationic
liposome has been developed.
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LPD-II encapsulated approximately
90% of the total doxorubicin, which was significantly enhanced
from that of LPD with guanidinium containing cationic lipid
(~10% entrapment). LPD-II could more efficiently deliver both
doxorubicin and siRNA than could non-targeted NPs or free drug.
The higher entrapment rate of doxorubicin in targeted NPs led
to a remarkable increase in uptake in the tumor and resulted in
an enhanced therapeutic effect by avoiding P-gp mediated drug
efflux.
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Simultaneous inhibition of both MDR and survival
signaling in cancer cells was achieved by co-delivery of doxorubicin
and a therapeutic siRNA using targeted LPD-II NPs. Since c-Myc
positively controls MDR expression,
135-137
down-regulation of MDR
could be achieved by silencing c-Myc. Besides c-Myc itself is known
as an oncogene; silencing of c-Myc may have an additional direct
anticancer effect. Co-delivery of both doxorubicin and c-Myc siRNA
in the same targeted LPD-II formulation significantly inhibited
tumor growth and enhanced tumor apoptosis in a synergistic
manner. Other formulations containing only c-Myc siRNA or only
doxorubicin had shown little therapeutic effect. c-Myc together
with doxorubicin in the non-targeted NPs had shown only a partial
inhibition of tumor growth, indicating that only the targeted NPs
with both doxorubicin and c-Myc siRNA could overcome the P-gp
mediated drug resistance.
134
3.4.1.4.3
LPH
The proper selection of biopolymer greatly influences the particle
condensation, size, and stability of the assembled NPs.
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The LPD
NPs used in previous studies incorporate a high molecular weight
polyanion carrier, calf thymus DNA, and successfully increase the
delivery efficiency (20-80%). The particle size is also reduced
(10-30%) when compared to the formulation without the carrier
DNA.
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Due to its low molecular weight, siRNA forms a loose and
unstable complex with a cationic carrier, such as a cationic polymer.
This problem can be avoided by incorporating a high molecular
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