Biomedical Engineering Reference
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polycation-deoxyribonucleic acid and anionic liposome-polycation-
deoxyribonucleic acid for systemic delivery of Dox and therapeutic
siRNA to MDR tumours to overcome the drug resistance for cancer
therapy [35]. For the first time they demonstrated that they could
co-deliver siRNA and a chemotherapeutic drug to drug resistant
tumours using two different multifunctional delivery systems.
3.5.3 Restoring Drug Sensitivity and Improving Efficacy in
Resistant Models
Before running the combination efficacy study in the tumours, we
first ran a pilot study with cisplatin alone to determine the optimum
cisplatin dose that can be used in the combination efficacy study. We
used HA-ODA/cisplatin, HA-ODA/HA-PEG/cisplatin along with
cisplatin solution in this study to pick the most potent/safe system
that can be used in the combination study. Our data indicated that
two, 1 mg/kg doses (4 days apart) gave a significantly better tumour
growth inhibition compared to the PBS treated group (approximately
35%) [23]. However, the efficacy was not as good as one would expect
with non-resistant tumours. Since these resistant A549 tumours are
resistant to cisplatin, the lower level of efficacy that we noticed was
not surprising. Overall, the HA-ODA/cisplatin system showed slightly
better efficacy than the other two at early time points. Based on this
observation, we selected this system for our combination efficacy
studies. Likewise, we also ran pilot studies to determine the doses of
both survivin and bcl-2 siRNA (unmodified and modified) to be used
in the efficacy study. Duration of activity and degree of knockdown
were determined in resistant A549 tumours using the HA-PEI/HA-
PEG system with both siRNA. Our data suggested that with three
consecutive siRNA doses (of 0.5 mg/kg), we were able to see about
50% gene knockdown in resistant A549 tumours at 72 h (after the
last dose) and it lasted for 5 days.
Based on the data that we gathered, we designed our combination
efficacy study with two rounds of treatment of HA-ODA/cisplatin and
HA-PEI/HA-PEG with survivin and/or bcl-2 siRNA to accommodate
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