Inovando com o uso da nanotecnologia
COSMÉTICOS
Silvia Stanisçuaski Guterres
Guterres, 2012
Nanocarriers and Nanomaterials
NC
Dendrimers
NS
SLN
Fullerenes
Liposomes
Carbon nanotubes
Guterres, 2012
Brazil
The cosmetics and toiletries sector
has shown an average growth of
10% annually over the past 18
years, moving from R$ 4.9 billion in
1996 to R$ 38 billion in 2013.
Brazil is a 41.7 billion dollars/year market
for cosmetics and personal care products,
which places the country as the 3rd
largest market in the world.
Guterres, 2012
Evolution of the Brazilian cosmetic market by
category in R$ (billions)
Category
2012
2013
2017
Total
85.1
92.1
142.5
Children's products
3.7
4.2
6.4
Soaps
6.5
7.0
9.6
Makeup
6.8
7.8
13.0
Deodorants and
antiperspirants
8.4
9.6
14.1
Depilatory products
0.7
0.8
1.5
Perfumes
12.6
14.2
21.5
Hair products
18.1
20.2
31.5
Male cosmetics
8.4
9.7
17.3
Oral hygiene products
6.6
7.6
11.9
Skin care products
8.9
10.3
15.7
Sunscreens
2.8
3.1
4.9
Guterres, 2012
Factors contributing to the impressive
growth of the sector:
 Increase of the population's income, with the new members of the
middle class beginning to consume products with higher added value
 Increase of the participation of women, who for 20 years represented
20% of income in the country and who now represent nearly half
 Increased use of new technologies and industrial productivity
 Intense and frequent launches of new products
 Increase in life expectancy, with increased demand for anti-aging
products
Guterres, 2012
Companies investing in
Nanotechnology in Brazil (2014)
Health
6%3%
7%
1%
8%
2%
Environment
Nanomaterials
Oil and Gas
46%
Energy/Eletronics
Aeronautical/Aerospace
Agribusiness and Food
22%
5%
Textile
Others
Healthcare companies investing in
Nanotechnology in Brazil (2014)
30 companies
23%
24%
Cosmetics
Pharmaceutics
Odontology
9%
Source: Ministry of Science,
Technology and Innovation.
3%
10%
Personal care
Nanomedicines
31%
Others
Guterres, 2012
The global market for cosmetics:
$155.8 million in
2012.[http://www.shb.com/newsevents/2011/Nan
oCosmeticsBeyondSkinDeep.pdf]
Widespread use of nanoscale
materials in cosmetics is due to
the fact that these nanoparticles
obtain newer properties which
differ from the large-scale
particles
J Pharm Bioallied Sci. 2012 Jul-Sep; 4(3): 186–193.
doi: 10.4103/0975-7406.99016
RANKING OF TOP 10 BEAUTY COMPANIES IN TERMS OF
NUMBER OF NANO-RELATED PATENTS
Guterres, 2012
Guterres, 2012
- control the release of drugs
- sustain the drug effect
- reduce toxicity
- target the drug to the site of action
- increase the drug stability
- increase of the intracellular traffic of drug
- increase the intracellular drug delivery
- increase the apparent solubility of drugs
- increase efficacy.
NANOTECHNOLOGY
IN COSMETICS
Good tool for
developing Sciencebased solutions for
innovative cosmetics
Essential for
marketing-oriented
companies
Enhancing wellbeing
Addressing antiaging issues
www.nanoreport.de/frame.html
A inserção da nanotecnologia na cadeia
produtiva.
NANOTECH IN COSMETICS
As an
ingredient
(nanoinsumo)
To be added in
a formulation
As product
As product
Final products:
suspensions,
aerosol, etc
Nanomaterials can be divided into two groups:
Soluble and/or
biodegradable
nanoparticles which
disintegrate into their
molecular components
Insoluble and/or
biopersistent
nanoparticles
e.g. liposomes and
nanoemulsions
e.g. TiO2, fullerenes,
quantum dots
Risk assessment
based on mass metrics
may be adequate for
the soluble
nanoparticles;
Risk assessment may
require other metrics,
such as the number of
particles, and their
surface area as well as
their distribution
Guterres, 2012
NANOTECH AS INGREDIENTS
NANOCARRIERS
Liposomes
Nanocapsules
Lipidic
nanoparticles
NANOMATERIALS
TioO2
Fullerenes
Ag
Cosmetic manufacturers use
nanoscale versions of ingredients
to provide
better UV
protection
deeper skin
penetration
long-lasting
effects
increased
color
NANOENCAPSULATION TECHNIQUES
products containing coated particles act as drug delivery systems
to control
the drug site of action
the kinetics of release of drug active substance
Guterres, 2012
NANOENCAPSULATION TECHNIQUES
NANO DELIVERY SYSTEMS
products containing coated particles act as drug delivery systems
To control the drug
delivery to the site of
action
To control the kinetics of
drug release
To dissolve/deaggregate
during or after releasing
the drug
Guterres, 2012
The role of a
nanoparticle-based
delivery system
To ensure
that a
chemical
Right
concentration
Right site
Correct period
of time
Guterres, 2012
“NANO-SKIN EFFECTS”
Sustained and controlled release of substances
nanodevices act as reservoirs
Reduction of cutaneous alernegicity
polymeric wall
Increase of cutaneous adhesion
prolonged effect
Stabilize labile substances
reservoir effects
Depend on
-shape and molecular
organization of
nanocarriers
-Size and polidispersity
-Surface coating
(hydrophilic or
lipophilic)
- surface area
NANOTEC: Multiplicidade de
formulações
PERFUMES; Esmaltes para unhas Shampoo, Pós-Shampoo
Coloração, Alisantes/Permanentes/Henês, Fixadores/Modeladores. condicionador, creme
para pentear, creme de tratamento, regenerador de pontas, definidor de
Tintura permanente
cachos.
, Tintura semi
permanente/tonalizante, Henna, Descolorante. Gel, Hair Spray ou Laquê,
Mousses
Cremes / Loções / ÓLEOS PARA O CORPO, Cremes de Tratamento para o
Corpo, Cremes para o Rosto, Protetor Solar, Bronzeador, Protetor Solar
Protetor Solar Labial
para o Rosto,
, Creme Esfoliante
para o Corpo, Creme ou Óleo para Massagem, Anti-Celulite, Creme
Contra Estrias, Loções Firmadoras, Creme para Gestantes, Creme para
Redução de Medidas. Hidratantes, Anti-Sinais / Anti-Age,
Esfoliantes, Adstringente, Anti-Acne, Tônicos, Cremes e
Loções de Limpeza.
Alguns exemplos
Lipid-core nanocapsules (LNC)
are formed by an organogel surrounded by poly(epsiloncaprolactone) and stabilized by polysorbate 80
An original
soft nanocarrier
Biodegradability: a
critical requirement for
nanoparticulate brain
delivery systems, i.e.
over a time
frame of a few days.
Web of Science
Access 2 september 2015
Articles
Nanocapsules and Drug
250
200
150
100
50
0
1985
1990
1995
2000
2005
FRANCE (308)
PEOPLES R CHINA (290)
BRAZIL (225)
2010
2015
2020
Web of Science
Access 2 september 2015
Articles
nano* and skin
total 5790
1200
1000
800
600
Articles
nano* and skin
Countries
400
200
0
1985
1990
1995
2000
2005
2010
2015
2020
1320
865
492
425
414
334
269
248
244
206
Gels showed non-Newtonian
behavior since their viscosities
were not constant
Shear stress (Pa)
90
80
GC-NM
70
GC
60
GNM-NE
50
GNM-NS
40
GNM-NC
30
20
10
0
2
4
6
8
10
12
200 nm
Gel + NC
0
14
Shear rate (s-1)
CRIOFRACTURE
•. Nanoemulsion, nanocapsules or nanospheres did not
affect the non-Newtonian behavior and the pseudoplastic
character of the gels
•The
gels
presented
adequate
physico-chemical
Gel ®
properties for the topical administration
Guterres et al. Pharmazie 2003
Guterres et al. Pharmazie 2005
Alves et al. IJP 2007
Which entity permates?
Drug vs Particle
SKIN PENETRATION FROM
NANOCARRIERS
Influence of the supramolecular structure
GNM-NC
NC
GNM-NS
6
GNM-NE
GC-NM
Amount Retained
μg/cm²
5
NS
4
3
2
NE
1
0
SC
Epiderm/Dermis
Receptor
compartment
•NC and NS: released into stratum corneum
•NE it was not quantified in SC, being permeated directly for dermis
•NC: in the deeper skin was larger than NS and that NE
200 nm
Polymeric nanocapsules
Nanocapsule
Drug encapsulation is limited by its
saturation in the organic phase.
Lipid-core nanocapsule
Drug encapsulation can be achieved
by its dispersion in the organic phase.
2011
The rigidity of both the polymer wall and lipid core is quantitatively higher for LNCs.
In conclusion, LNCs presented distinct elastic properties compared to the conventional polymeric NCs.
Cantilever Deflection
Nanocapsule (NC)
Cantilever Deflection
Lipid-core Nanocapsule (LNC)
Tese: Luana Fiel
Control of skin penetration
Rhodamine B
covalently bound to
PCL
horny layer
(X,Z)
epidermis
basal layer
(X,Z)
dermis
CO-ENCAPSULATION OF CAPSAICINOIDS AND
INCORPORATION IN A CHITOSAN HYDROGEL
CAPSAICIN
Capsicum spp.
DIHYDROCAPSAICIN
POLYMERIC NANOCAPSULES
Analgesic topical action when reaching the peripheral
nerves, used for the treatment of chronic pain.
Physically stable formulation
containing intact nanocapsules;
Consistence and pH suitable for
cutaneous use;
Controlled release of capsaicinoids;
Film formation proven by sensorial
studies;
CHITOSAN HYDROGEL CONTAINING
NANOCAPSULES
Great skin adhesion
Guterres, 2012
Decrease on the skin irritation in humans of capsaicinoids by means of a
nanostructured formulation based on polymeric particles and a hydrogel
CH- NC- CP
CH- ET- CP
Erythema (Final/Initial)
2,50
COMMERCIAL
CH- NC
2,00
CH- ET
NO FORMULATION
1,50
1,00
0,50
0,00
0
30
60
90
120
150
180
Time after application (min)
CH- NC- CP
6
CH- ET- CP
COMMERCIAL
Erythema
5
CH- NC
CH- ET
4
NO FORMULATION
3
2
1
0
0
50
100
150
200
Time after application (min)
Guterres, 2012
Nanocapsules: Stabilizing properties
Guterres, 2012
Resveratrol
Poor bioavailability and ease
degradation
a red wine polyphenol
Protector effect against cardiovascular diseases
and cancers
improved
Antiaging effects
Modulation of multiple mechanisms of
Alzheimer's disease
Formulation
T 12 (mim)
Resveratrol ethanolic solution
Resveratrolloaded LNC
19.5 ±3.7
122.6 ±16.3
Volume 88, Issue 4, pages 913–921, July/August 2012
Nanocapsules: Sustaning the effect
NANOANESTÉSICO
Nanotecnologia e produtos naturais:
uma combinação inovadora para
insumos e produtos cosméticos
O Brasil é o país com maior
diversidade biológica do mundo.
> 22% do total de espécies vegetais
e um terço das espécies de
pássaros do planeta
Entre 43000 and 49000 espécies vegetais
catalogadas das cerca de 350000 – 500000
existentes
• 70% of entrepreneurs said that biodiversity is
important to their business, especially Bolivians and
Brazilians with 85% and 80%, respectively.
A survey
• And over 94% of respondents in Brazil, Colombia and
Peru said the interest in natural ingredients will
increase over the next 10 years.
• Most companies in the studied countries (80%) bet
on natural ingredients as a source of technological
innovation in their products.
In Brazil, biodiversity is on the radar,
especially in the cosmetics industry.
http://www.brazilbeautynews.com/entrepreneurs-see-biodiversity-as-part-of-their,274
Biodiversidade como “o cofre de um patrimônio
químico
inexplorado de remédios, alimentos, fertilizantes, pesticidas,
cosméticos, solventes, fermentos, têxteis, plásticos, celulose, óleos e
energia, além de moléculas, enzimas e genes em número quase infinito”.
Arnt (2001)
Biodiversidade pode ser entendida como uma
preciosa “biblioteca
genética”
Apenas em torno de 10% da biodiversidade
mundial foi estudada.
Calixto (2000)
ANTIOXIDANTES TÓPICOS
• Os antioxidantes tópicos devem ser
absorvidos pela pele e liberados para o
tecido-alvo na forma ativa.
• Entretanto, muitos produtos se oxidam e
se tornam inativos antes mesmo de
alcançarem o alvo.
• A absorção é um processo muito
importante e depende de vários outros
fatores, como, por exemplo, a forma
molecular do composto ativo, suas
propriedades físico- químicas, se sua
solubilidade em água ou em lipídeos, seu
pH e o veículo que contém o produto.
A maioria é origem
vegetal
Ser capaz de
permear o
estrato córneo
Isento de
toxicidade
local e
sistêmica
Apresentar
efeito antioxidante
pronunciado
ANTIOXIDANTES
REQUISITOS
Características
físico-químicas
para incorporação
em formulações
tópicas
Ser
fotoestável
Manter-se
estável no
produto final
FABRICAÇÃO DE NANOPARTÍCULAS
Matérias
primas de
origem vegetal
Materiais
estruturantes
Ativos
Theospheres,
a brazilian nanoparticle
Cupuaçu (Theobroma grandiflorum)
One of the most popular Amazon fruit
Components
Unsaturated fatty acids
Vitamins
Amino Acids
Phytosterols (water absorption capacity)
Cosmetic uses
Deep sink hydration
Horn layer lipid reposition
Nanoencapsulação de
substâncias de origem vegetal
ÓLEOS VEGETAIS COMO NÚCLEO DE NANOCÁPSULAS: UMA
ESTRATÉGIA PARA TORNÁ-LOS DISPERSÍVEIS EM FORMULAÇÕES
HIDROFÍLICAS
Lipid core Nanocapsules
Mango
Jojoba
Pequi
Oat
Annato
Calendula
Chamomile
Capric/caprylic triglycerides
D[4,3] (nm) (LD)
226 ± 33
187 ± 8
230 ± 59
203 ± 33
214 ± 27
242 ± 20
193 ± 6
166 ± 8
NOVAS
SOLUÇÕES
AUMENTO DA
EFICÁCIA
NANO
E FITO
INOVAÇÃO
MAIOR
ESTABILIDADE
NANOTECHNOLOGY
IN SUNSCREENS
•Formulations are more transparent
and less oily
•Increases the sunscreen retention
time in the skin due to an increase of
bioadhesion
•Reduce the skin penetration of the
filters
•Provide a controlled release of the
filters
•Reduce the sensitization of chemical
filters
Articles
Citations: 505
(Web of Science)
Tópico: (nano* and sunscree*)
Patents
Citations: 263
(Tópico: (nano* and sunscree*).
Guterres, 2012
A SUCCESSFUL EXAMPLE OF
NANOPRODUCT ON THE MARKET
Nanocapsules
Biodegradable
polymeric wall
Vegetal oils
Organic sunscreens
Photostability
NANOPHOTON®TECHNOLOGY
Photoprot containing
nanocapsules
Photoprot without
nanocapsules
Photoprotection
Photostability
Nanoencapsulated UV filters
UV-blocking ability
UV blocking mechanism (scattering + absorbing)
obtained with nanoencapsulated UV filters.
Nanoencapsulated sunscreens have higher SPF values than the
free sunscreen and the unloaded polymeric and lipid nanocarriers.
Guterres, 2012
Guterres, 2012
Collaborators
Adriana R. Pohlmann, UFRGS
Ana M. O. Battastini, UFRGS
Andressa Bernardi, Fiocruz
Carlos Alexandre Netto, UFRGS
Christianne Salbego, UFRGS
Dulcineia S. P Abdalla, USP
Maria Palmira Gremião, Unesp
Marilise Burger, UFSM
Nádya P. da Silveira, UFRGS
Renata Limberger, UFRGS
Rudimar Frozza, Fiocruz
Ruy C. R. Beck, UFMS e UFRGS
Sandra Farsky, USP
Solange C. Garcia, UFRGS
Stela Rates, UFRGS
Teresa Dalla Costa, UFRGS
OUR LABORATORY
College of Pharmacy
UFRGS
•HPLC
•Zetasizer@
•Turbscan ®
•GC-MS(MS)
• Nanosizer®
•Freeze-drier
•Spray-drier
•Spraytec
•SEM
•TEM
•Animal models
•Microbiological
analyses
•IV
•NMR
•Viscosimeter
•Dissolutor
[email protected]