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Division of Molecular Therapeutics and Formulation
School of Pharmacy, University of Nottingham
Vectura Group plc
Alejandro Nieto-Orellana
Protein Therapeutics
2http://ww1.prweb.com/prfiles/2011/06/14/8893206/biosimilar_injectable.jpg
Protein Therapeutics
3
http://www.vectura.com/technologies/device-technologies/
4
Pulmonary protein delivery: challenges
https://aapsblog.aaps.org
http://nanogloss.com/tag/white-light-nanoparticles/#axzz4RlvVAXno`
http://i.ndtvimg.com/i/2015-12/lungs-generic_650x400_51450598122.jpg
5
Pulmonary protein delivery: challenges
Polymer-based Nanosystems
6
Polymer-based Nanosystems
7
-- - -
8
Polymer-protein nanocomplexes
N3H+
+
https://www.quora.com/Why-are-protein-structures-represented-by-a-ribbon-cartoon
Copolymers used in this study
9
Copolymers used in this study
10
Formation of polymer-protein nanocomplexes
11
0 2 0 0 4 0 0 6 0 0 8 0 0
0 .0
0 .5
1 .0
1 .5 L 1 0 -L y s
H y d ro d y n a m ic d ia m e te r (n m )
Co
nc
en
tra
tio
n
(E6
pa
rtic
le/m
l)
0 2 0 0 4 0 0 6 0 0 8 0 0
0 .0
0 .5
1 .0
1 .5
2 .0
2 .5 L 3 0 -L y s
H y d ro d y n a m ic d ia m e te r (n m )
Co
nc
en
tra
tio
n
(E6
pa
rti
cle
/ml)
0 2 0 0 4 0 0 6 0 0 8 0 0
0
1
2
3
4 M 3 0 -L y s
H y d ro d y n a m ic d ia m e te r (n m )
Co
nc
en
tra
tio
n
(E6
pa
rti
cle
/ml)
0 2 0 0 4 0 0 6 0 0 8 0 0
0
1
2
3
4
5 M 9 0 -L y s
H y d ro d y n a m ic d ia m e te r (n m )
Co
nc
en
tra
tio
n
(E6
pa
rti
cle
/ml)
109 ± 61 nm 146 ± 42 nm
183 ± 111 nm 159 ± 158 nm
Formation of dry powders from nanocomplexes suspension
12
µ
Ly
s
L1
0-L
ys
L3
0-L
ys
M3
0-L
ys
M9
0-L
ys
0
2 0
4 0
6 0
8 0
1 0 0
E m it te d d o s e
ED
(%
)
Lys
L10-L
ys
L30-L
ys
M30-L
ys
M90-L
ys
0
2 0
4 0
6 0
8 0
1 0 0
F in e P a r t ic le F ra c t io n
FP
F (
%)
Aerosol properties of the different dry powders
13
Recovery of nanocomplexes from dry powder
formulations
14
0 2 0 0 4 0 0 6 0 0
0
2 0
4 0
6 0
8 0
1 0 0
N a n o c o m p le x e s B E F O R E fo rm u la tio n
in to d ry p o w d e rs
H y d ro d y n a m ic d ia m e te r (n m )
No
rm
ali
se
d P
arti
cle
Co
nc
en
tra
tio
n
0 2 0 0 4 0 0 6 0 0
0
2 0
4 0
6 0
8 0
1 0 0
N a n o c o m p le x e s R E C O V E R E D
fro m d ry p o w d e rs
H y d ro d y n a m ic d ia m e te r (n m )
No
rm
ali
se
d P
arti
cle
Co
nc
en
tra
tio
nL 1 0 -L y s
L 3 0 -L y s
M 3 0 -L y s
M 9 0 -L y s
Lys
L10-L
ys
L30-L
ys
M30-L
ys
M90-L
ys
0
2 0
4 0
6 0
8 0
1 0 0
1 2 0
E n z y m a tic a c tiv ity A F T E R
n a n o c o m p le x e s d is s a s e m b ly
No
rm
ali
se
d
en
zy
ma
tic
ac
tiv
ity
(%
)
Recovery of nanocomplexes from dry powder
formulations
15
Lys
L10-L
ys
L30-L
ys
M30-L
ys
M90-L
ys
0
2 0
4 0
6 0
8 0
1 0 0
E n z y m a tic a c tiv ity o f
n a n o c o m p le x e s
No
rm
ali
se
d
en
zy
ma
tic
ac
tiv
ity
(%
)
Protection against proteolytic degradation
16
Lys
L10-L
ys
L30-L
ys
M30-L
ys
M90-L
ys
0
2 0
4 0
6 0
8 0
1 0 0
1 2 0
P ro te in p ro te c tio n
No
rma
lis
ed
en
zy
ma
tic
ac
tiv
ity
(%
)
****
Immunogenicity
17
Lys
L30-L
ys
M30-L
ys
0
2 0
4 0
6 0
Co
mp
lem
en
t a
cti
va
tio
n (
%)
****
18
19
THANK YOU FOR YOUR ATTENTION
Alejandro Nieto-Orellana
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