safer-by-design strategies in guidenano - cea/nanosafe 3.2/ps3.2... · potential to cross...
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Beatriz Macarena Cobaleda Siles, PhDNANOSAFE 2016
Grenoble, 7-10 November
Safer-by-Design strategies in GUIDEnano
Safety by Design
Human learning: Trial-and-error approach + bad decision
Synthesis of product
Toxic metals and environmentally
unfriendly
Change the regulatory
rules
Design safer product
Safety by Design
Design safer product
Synthesis of product with toxic
metals andenvironmentally
unfriendly
1. Safety is addressed at the design stage of a process or product rather thantested after their development
2. Not develop toxic technologies3. Design or re-design protocols to avoid make mistakes
Angew. Chem. Int. Ed. 2014, 53,2-18
http://www.safenano.org
State of the art
Int. J. Nanomedicine. 2015,10,3989-4008
Safer by Design strategiesDeveloped to modulate the main factors determining safety of NMs: • Intrinsic toxicity • Release/bioavailability potential• Persistence
To reduce toxicity of NMs:- Shape and size modifications- Increase in hydrophilicity to decrease thepotential to cross biological membranes- Changing oxidation state to mitigatereactivity
To reduce release of NMs from theirmatrices:- Induction of strong Van der Waalsand covalent bonding between theNMs and their matrices- Development of barriers bymultilayer approaches (multilayerfilms) or multicoating approaches- Self-healing pairs of NM/matrix byionic approach to avoid release ofNMs
To reduce persistence of NMs:- Induction of self-assembly of NMs to increase the coalescent character of the NMsin aqueous media or at high temperatures to promote the sintering intomicroaggregates- Development of new high biodegradable NMs under certain temperature oroxidative conditions
Environ. Sci.: Processes Impacts, 2013, 15, 23
Physico-chemical Characteristics of NMs
• Green Chemistry• Design to avoid changes in the activity orproperties• Proper and extense physico-chemicalcharacterization
Reducing toxicity of NMs
nanomicro
Size ≥ 10 µm
Control of Nanoparticle aggregation
Ionic strengthpH of the dispersionSurface charge
Size modifications
Frustrated phagocytosis
J. Environ. Sci. Health Part A, 2009, 44, 1485–1495Particle and Fibre Toxicology, 2010, 7:5
Reactivity
T iO 2 _ In d iv id u a l_ 1 5 n m
W a v e le n g th (n m )
Ab
so
rb
an
ce
3 0 0 4 0 0 5 0 0 6 0 0 7 0 0 8 0 0
0
1
2
3
T iO 2 _ S m a ll_ 5 0 n m
W a v e le n g h t(n m )
Ab
so
rb
an
ce
3 0 0 4 0 0 5 0 0 6 0 0 7 0 0 8 0 0
0
1
2
3
T iO 2 _ L a r g e _ 1 1 6 n m
W a v e le n g th (n m )
Ab
so
rb
an
ce
3 0 0 4 0 0 5 0 0 6 0 0 7 0 0 8 0 0
0
1
2
3
A U C T iO 2 3 0 0 -8 0 0 n m
T im e (h )
AU
C
0 5 1 0 1 5 2 0 2 5 3 0 3 5
0
1 0 0
2 0 0
3 0 0
T iO 2_ In d iv id u a l_ 1 5 n m
T iO 2_ S m a ll_ 5 0 n m
T iO 2_ L a rg e _ 1 1 6 n m
Sedimentation of TiO2
A g N P _ 1 5 n m
W a v e le n g th (n m )
Ab
so
rb
an
ce
3 0 0 4 0 0 5 0 0 6 0 0 7 0 0 8 0 0
0 .0
0 .2
0 .4
0 .6
0 .8
1 .0
1 .2
1 .4
W a v e le n g th (n m )
Ab
so
rb
an
ce
3 9 0 3 9 5 4 0 0 4 0 5 4 1 0 4 1 5
1 .0 01 .0 2
1 .0 4
1 .0 6
1 .0 8
1 .1 0
1 .1 2
1 .1 4
1 .1 6
1 .1 8
1 .2 0
1 .2 2
1 .2 4
1 .2 6
1 .2 8
1 .3 0
A g N P _ 5 0 n m
W a v e le n g th (n m )
Ab
so
rb
an
ce
3 0 0 4 0 0 5 0 0 6 0 0 7 0 0 8 0 0
0 .0
0 .2
0 .4
0 .6
0 .8
1 .0
1 .2
W a v e le n g th (n m )
Ab
so
rb
an
ce
4 2 0 4 3 0 4 4 0 4 5 0 4 6 0
1 .0 5
1 .1 0
1 .1 5
A g N P _ 1 5 0 n m
W a v e le n g th (n m )
Ab
so
rb
an
ce
3 0 0 4 0 0 5 0 0 6 0 0 7 0 0 8 0 0
0 .0
0 .2
0 .4
0 .6
A U C A g N P 3 0 0 -8 0 0 n m _ 4 8 h
t im e (h )
AU
C
0 5 1 0 1 5 2 0 2 5 3 0 3 5
5 0
1 0 0
1 5 0
2 0 0
2 5 0
A g N P 1 5 n m
A g N P 5 0 n m
A g N P 1 5 0 n m
Sedimentation of Ag
Reducing release of NMsRisk assessment: The release of NMs from their matrices. Objective: avoid the release of the NM or release as ions. Procedure: Protect the NP using polymer coatings (PVP)
Nano Lett., 2015, 15 (1), 365–371
AgNW-cloth overall emissivity is much less than that of normal cloth and provides greatinsulation against radiative heat loss (higher IR reflectance and thermal insulation capability)
Reducing release of NMs
“Several studies have shown that AgNP suspensions are toxic. However, there have been no systematic studies, which analyze to which degree varying amounts of silver ions
present in AgNP suspensions contribute to their toxicity”
Risk assessment: The ion release is more toxic than the NP. Objective: avoid the degradation of the NM. Procedure: Protect the NP using coating ligands
Environ Sci Nano., 2014, 1(2), 144–153.
Safer-by-design nanostructured materials
• ZnO NPs absorb UV wavelengths ranging from 280 to 400 nm (ideal component in cosmetic creams and sunscreens)
• Generation of reactive oxygen species (ROS) which led to DNAdamage, cell viability reduction, and apoptosis (released ions anddirect particle interactions with cells)
• SiO2 shell exhibits less DNA damage in comparison to the uncoatedones
• Minimizing the ZnO nanoparticle dissolution and direct contact withthe cells inhibiting toxicity
Reducing persistance of NMs
• The addition of protective agents to avoid the spontaneous transformation of NMs, forinstance using albuminization strategy.
• Studying the transformation of NMs and their corresponding toxicity by changing the NMcomposition, such as Ag+ and Ag2S in the presence of S2- ions.
Controlling and monitoring the evolution of NMs
AgNP
Ag2S
+ coating ligand
albumin
Nature Nanotechnology, 2009, 4, 546 – 547J. Nanobiotechnol, 2015, 13, 84
A g N P _ 1 5 0 n m _ H 2 O 2
W a v e le n g th (n m )
Ab
so
rb
an
ce
3 0 0 4 0 0 5 0 0 6 0 0 7 0 0 8 0 0
0 .0
0 .1
0 .2
0 .3
0 .4
t0
t60
t1 20
t1 80
t2 40
t3 00
t3 60
t2 1h
t2 4h
t2 8ht4 8h
Corrosion of Ag
N 2
W a v e le n g th (n m )
Ab
so
rb
an
ce
3 0 0 4 0 0 5 0 0 6 0 0 7 0 0 8 0 0
0 .0
0 .2
0 .4
0 .6
0 .8
1 .0
D M E M
W a v e le n g th (n m )
Ab
so
rb
an
ce
3 0 0 4 0 0 5 0 0 6 0 0 7 0 0 8 0 0
0 .0
0 .2
0 .4
0 .6
0 .8
1 .0
H 2 O 2
W a v e le n g th (n m )
Ab
so
rb
an
ce
3 0 0 4 0 0 5 0 0 6 0 0 7 0 0 8 0 0
0 .0
0 .2
0 .4
0 .6
N 2
W a v e le n g th (n m )
Ab
so
rb
an
ce
3 0 0 4 0 0 5 0 0 6 0 0 7 0 0 8 0 0
0 .0
0 .1
0 .2
0 .3
0 .4
D M E M
W a v e le n g th (n m )
Ab
so
rb
an
ce
3 0 0 4 0 0 5 0 0 6 0 0 7 0 0 8 0 0
0 .0
0 .1
0 .2
0 .3
0 .4
H 2 O 2
W a v e le n g th (n m )
Ab
so
rb
an
ce
3 0 0 4 0 0 5 0 0 6 0 0 7 0 0 8 0 0
0 .0
0 .1
0 .2
0 .3
0 .4
N 2
W a v e le n g th (n m )
Ab
so
rb
an
ce
3 0 0 4 0 0 5 0 0 6 0 0 7 0 0 8 0 0
0 .0
0 .5
1 .0
1 .5
2 .0
D M E M
W a v e le n g th (n m )
Ab
so
rb
an
ce
3 0 0 4 0 0 5 0 0 6 0 0 7 0 0 8 0 0
0 .0
0 .1
0 .2
0 .3
H 2 O 2
W a v e le n g th (n m )
Ab
so
rb
an
ce
3 0 0 4 0 0 5 0 0 6 0 0 7 0 0 8 0 0
0 .0 0
0 .0 2
0 .0 4
0 .0 6
0 .0 8
0 .1 0
Development of biodegradable NMs under certain temperature or oxidative conditionsAgNP_15 nm AgNP_50 nm AgNP_150 nm
Safer not Safe or safety by design
Proper and extense characterization of NMs to obtain an optimal design
Controlling and monitoring our NMs “from cradle to grave”
Controlling the size, shape, possible oxidation states during lifecycle….
Controlling the release of the NM from the solid/of the ions from the NM
Controlling the persistance of NMs: transformation, corrosion,…
Solid is a friend, aqueous solution is an ally but airborne is the enemy
Safety aspects should inform about the design of a product or process at theinception point, along with other key concepts such as function, quality and cost
Conclusions
The outcomes reflected in this work were performed under the ongoing GUIDEnano project funded by European Commission´s Framework Programme
(FP7/2007-2013) under grant agreement №604387
Design and Pharmacodynamic of Nanoparticles Group
Acknowledgment