gallo et al (iser 2012)
TRANSCRIPT
Emiliano S. Lopez , Oscar J. Croxatto, Juan E. Gallo
Facultad de Ciencias Biomédicas, Universidad Austral; Oftalmologia, Hospital Universitario Austral , Pilar- Buenos Aires ; Patologia Ocular, Fundación Oftalmológica Argentina "Jorge
Malbran", Buenos Aires, Argentina.
SURAMAB
- EP 2186529; granted 28 March 2012.
- US Patent pending.
BevacizumabBevacizumab
SuraminSuramin
We have previously shown that Suramab, a novel pharmaceutical compound, has antiangiogenic properties.
ES Lopez , MM Rizzo, JO Croxatto , G Mazzolini , JE Gallo. Suramab, a novel antiangiogenic agent, reduces tumor growth and corneal neovascularization. Cancer Chemother Pharmacol 2011; 67:723–728
To analyse the role of VEGF, bFGF, LYVE-1 and P2X2 in the antiangiogenic mechanism of suramab in a rabbit model of corneal neovascularization.
9 Rabbits 9 Rabbits 9 Rabbits
Photographs d9 d15 d21 d35
Anesthesia filter disc (7mm) Na(OH) 1M (1min) Wash SB
-L. David Ormerod. Standard Models of Corneal Injury Using Alcali-Inmersed filter discs. Investigative Ophthalmology & Visual Science, Vol. 30, Nº. 10, October 1989.
Suramab Bevacizumab Control
DAY 9
DAY15
DAY 35
CLINICAL FOLLOW-UP
Rabbits treated with Suramab Suramab showed a lower neovessel index than that seen in controls at 35 days (T student, p<0.0001).
Suramab Suramab had a greater antiangiogenic effect than that seen in animals treated with Bevacizumab Bevacizumab (T student, p<0.02).
Suramab Control
CONTROL TREATED GROUPS
SuramabControl Bevacizumab
S C B
42kDa
43kDa
VEGF
ACTIN
SURAMABSURAMAB BEVACIZUMAB CONTROLBEVACIZUMAB CONTROL
S C B
LYVE-140 kD
ACTIN 43 kD
Bevacizumab SuramabControl
50kD
43kD
P2X2
ACTIN
C S B
B C S
B C S
bFGF
ACTIN
43 kD
19 kD
Western Blot
- Suramab has a strong antiangiogenic effect.
- VEGF, P2X2, LYVE-1 and bFGF are involved in the antiangiogenic mechanism.
CONCLUSIONS
CONTROL
Clinical evolution
Control S
S+P0
10
20
30
40
50
Groups ( 14 days postinjury)
Are
a o
f N
V (
%)
ControlControl 38.22 35.3 30 29 31 22
SuramabSuramab 19.4 3 6 5 8 9
S+PS+P 5 0 1 2 1 1
Control Suramab+P Suramab
- Drug delivery systems are being currently developed to improve suramab ´s performance in the treatment of corneal and retinal neovascularization.
CONCLUSIONS
THANK YOU!
3 Conejos 3 Conejos 3 Conejos
Control Suramina EV Bevacizumab
DIA 9
DIA 35
Evolución clínicaEvolución clínica
Días post-lesión
INV
pro
med
ios
P407/P188 VehículoPolímero% (w/w)
T gel I (°C)
T gel II (°C)
Viscosidad a 35°C (Pas)
(24/20)%w/w
NaCl 0.9% 26,4 27,9 14100
NaCl 0.9%0,5 (Chitosan)
24,8 26,4 17800
NaCl 0.9% 0,25 (Hialuronato de Sodio)
25,3 27,9 14100
1,00E-01
1,00E+00
1,00E+01
1,00E+02
1,00E+03
1,00E+04
0 5 10 15 20 25 30 35 40 45
Viscosity (Pa.s)
Temperatura °C
P407/P188/NaCl/Chitosan (24/20/0.9/0.5 % w/w)
Poloxamers
Poloxamers-Hialuronato
Poloxamers-Chitosan
Dr. Santiago Palma, Daniela Quinteros. Universidad Nacional de Cordoba