Combinatorial-designed Hyaluronic Acid Nanoparticles for Tumour Targeted Drug and Small Interfering Ribonucleic Acid Delivery - Hyaluronic Acid for Biomedical and Pharmaceutical Applications - page 82

the activity of both treatments. In addition to the therapeutic small
interfering ribonucleic acids, this study also included non-therapeutic
control siRNA in the same delivery system combined with cisplatin
treatment to exclude the non-specific activity [23] ( Figure 3.8 ).

a

HA/cisplatin
(1mg/kg)

d1 d2 d3 d4 d5 d6 d7 d8 d9 d10 d11 d12 d13 d14

HA/si RNA (0.5mg/kg)

b

1600

cisplatin vs . bc2+cisplatin

cisplatin vs . survivin+cisplatin

1600

1400

1400

1200

~31%

1200

1000

31%
52%

1000 PBS

PBS

800

800

~58%

HA/cisplatin

HA/cisplatin

600

600

HA/bcl-2

HA/survivin

400 400

HA/survivin
+HA/cisplatin

HA/bcl-2+HA/cisplatin

200

200

0

0

6 8 10 12 14

Days post implantation

16 18 20 22 24

6 8 10 12 14

Days post implantation

16 18 20 22 24

1600

cisplatin vs .
bc12+survivin+cisplatin

cisplatin vs . CTL+cisplatin

1600

1400

1400

1200

~31%

1200

~29%
~31%

1000 PBS

1000

800

PBS HA/cisplatin

800 ~62%

600

HA/CTL HA/bcl-2+HA/survivin

600

HA/CTL+HA/cisplatin 400 HA/survivin+HA/bcl-2+

HA/cisplatin

400

HA/cisplatin

200

200

0

0

6 8 10 12 14

Days post implantation

16 18 20 22 24

6 8 10 12 14

Days post implantation

16 18 20 22 24

Figure 3.8 Effect of combination of down-regulation of two
anti-apoptotic genes (survivin and bcl-2) and cisplatin treatment.
The dose regimen was designed based on the pilot studies (doses
d1-d14) (a). Mice bearing A549 DDP tumours were treated with
nine different combinations as described (five mice per treatment
group) for over 2 weeks and the tumour growth and other
safety measurements were monitored. Comparison of the anti-
tumour efficacy of cisplatin treated mice with survivin+cisplatin
treated mice, cisplatin treated mice with bcl-2+cisplatin
treated mice, cisplatin treated mice with CTL siRNA+cisplatin
treated mice, cisplatin treated mice with survivin+cisplatin and
survivin+bcl-2+cisplatin treated mice (b). Adapted from S. Ganesh,
A.K. Iyer, J. Weiler, D.V. Morrissey and M.M. Amiji, Molecular
Therapy-Nucleic Acids , 2013, 2 , e110 [23]