SKIN PROTECTION BEYOND UV RADIATION

SOLAR RADIATION UV

IR

VIS

7% 39%

54%

Excessive exposure to solar radiation leads to premature skin aging, as well as other skin disorders including skin cancer.

SKIN PENETRATION OF SUN LIGHT UV NAME

WAVELENGTH (nm)

PHOTON ENERGY (eV)

Ultraviolet

290 — 400nm

3 — 124 eV

Visible light

400 — 760nm

1.7 — 3.3 eV

760 — 1mm

1.24meV — 1.7 eV

Infrared

VIS and IR light penetrate deep in the dermal layers where the proteins responsible for skin structure are formed.

VIS

IR

CURRENT SUN PROTECTION Sunscreens: protection focused on UV radiation •

Mechanism:

Absorption of UV photons, reflection of photons and scatterring by nanoparticles •

Protects efficiently against sunburn caused by UVB

•

Constant improvements to combat the dermal damage caused by UVA

•

Recent launches include IR and free radical (FR) protection

•

However, the current sunscreens do not provide enough protection against free radicals. Current sunscreens neutralise FR generated in the skin surface, but not the FR produced in the deeper layers.

FREE RADICALS AND SKIN AGEING Excessive exposure of the skin to sun rays leads to the formation of free radicals (FR) and to the breakdown of collagen, the major structural component of the skin. These are the main causes of premature skin ageing, characterised by sagging and the appearance of wrinkles. The skin has protection mechanisms to neutralise FR. However, if the number of radicals formed is significantly increased, this defence mechanism is not able to neutralise. In order to avoid premature skin aging, products should reduce the free radicals and the degradation of collagen fibres.

RECENT SCIENTIFIC FINDINGS

“50% of free radicals are produced in the visible and IR range.” (Zastrow et al., Pharmacol Physiol 2009)

“Although the energy of IR photons is not high enough to for radical production, biological systems accumulate the IR energy up to a level that is sufficient to produce free radicals.” “IR cause photoaging by diminishing the skin’s anti-oxidant capacity and up-regulating the MMP1 enzyme, responsible for the breakdown of collagen, the major structural component of the skin. (Darvin et al., Exp Dermatol 2010) “Visible light also induces free radicals and matrix metalloproteinase (MMP)-1 expression contributing to premature photoaging.” “Commercially available sunscreens were found to have a minimum effect on reducing visible light -induced free radicals”. (Liebel et al., J Invest Dermatol 2012) “Damage caused by UV radiation continues to occur hours after sun exposure”. (Premi et al., Science 2015)

BIOLOGICAL SUN PROTECTION Biological Sun Protection consists in reinforcing the skin defence mechanism enabling the tissue to neutralize the harmful effects of solar radiation. The extra supply of antioxidant molecules is one of the main strategies to protect the skin from free radicals. When the skin defence is boosted, the protection is extended to any source of FR formation (UV, VIS, IR, etc.) and any time of the day, in a 24h protection.

An efficient Sun Protector should provide the skin with tools to combat the free radical formation induced by any source and during the 24h of the day.

BICOTENE® ANTIOX UV&IR PROTECTION COMPLEX Bicotene® Antiox is a smart skin care ingredient developed with Bicosome® Technology for Biological Sun Protection.

Bicotene® Antiox is able to reach the deeper layers of the epidermis nourishing the skin with a powerful combination of stable carotenes and antioxidant vitamins (AOs).

Bicotene® Antiox reinforces the skin defence mechanism providing UV, Vis & IR free radical protection and protects skin collagen from degradation, preventing the signs of aging.

BICOSOME® TECHNOLOGY An Intelligent Biomimetic Skin Delivery System Smart disc shaped structures Smart disc shaped structures

Lipid vesicle

Cryo-TEM image of a Bicosome.

BICOSOME® BIOMIMETIC MECHANISM

* (Barbosa-Barros, L., 2008)

Technique: CRYO SEM

TARGETING SKIN LAYERS BICOSOME PROTOTYPE 1

BICOSOME PROTOTYPE 2

BICOSOME PROTOTYPE 3

Deepness of penetration and retention: Stratum corneum

Deepness of penetration and retention: Epidermis

Deepness of penetration and retention: Dermis

* Fluorescence microscopy images of three different Bicosome systems encapsulating sodium fluorescein.

TARGETING OF BICOTENE® ANTIOX Technique: FLUORESCENCE MICROSCOPY

WHY CAROTENES? Carotenoids and vitamins form the basis of our non enzymatic defence mechanism against free radical formation. Betacarotene protects the immune system and DNA from UV-induced free radical damage and by increasing the minimal erythema dose. Betacarotene is the most abundant and the most efficient precursor of vitamin A. It is also known as Pro- vitamin A. The extra supply of topical Carotenes can reinforce the skin defence mechanism to combat free radical formation and naturally stimulates skin biological processes in several levels.

INSTABILITY OF CAROTENES AND VITAMINS The limitation of carotenes and antioxidant vitamins in topical formulations resides on their poor stability in topical formulations. If not formulated in adequate systems, these molecules are quickly inactivated.

BETACAROTENE MOLECULE

Carotenes are potent antioxidants. However, topical formulations with these molecules are limited due to their instability.

BICOTENE® ANTIOX STABILISES CAROTENES

Bicotene® Antiox was designed to incorporate and stabilise Carotenes and vitamins and to transport them to the deeper layers of the epidermis.

0h 2h

NON-ENCAPSULATED BETA-CAROTENE

Without protection, Beta-carotene peaks completely disappear after 2hs of UV irradiation.

0h 2h

BICOTENE® ANTIOX

Technique: RAMAN SPECTROSCOPY

Bicotene® Antiox preserves the Betacarotene molecules. After 2h of UV irradiation the peaks of beta-carotene are practically identical.

BICOTENE® ANTIOX SKIN PENETRATION LIPOSOMES + BETACAROTENE

BICOTENE® ANTIOX

During and after sun exposure high amounts of FR are produced in the epidermis. Most sunscreens are not able to neutralise FR beyond skin surface. Bicotene® Antiox penetrates the skin and delivers its content into the deepest layers of the epidermis. Bicotene® Antiox delivers Beta-carotene 8X deeper than a classical liposome system.

Penetration : 40 µm 10 µM

- carotene

Technique: RAMAN MICROSCOPY

Penetration: 5 µm 10 µM

+ carotene

BICOTENE® ANTIOX COLLAGEN PROTECTION 4

10

Native skin before IR Native skin after IR Skin treated with Bicotene® Antiox after IR

“IR cause photoaging by diminishing the skin’s anti-oxidant capacity and upregulating the MMP- 1 enzyme, responsible for the breakdown of collagen, the major structural component of the skin.” Darvin et al. 2010

3

I (q) (a.u.)

10

IR PROTECTION

2

10

1

10

0

10

-1

10

0.3

0.6

q/nm Technique: SMAL L ANGLE X-RAY SCATTERING (SAXS)

0.9

Bicotene® Antiox protects the skin collagen from degradation induced by IR radiation, helping to avoid the signs of photoaging such as sagging and wrinkles.

BICOTENE® ANTIOX FREE RADICAL (FR) PROTECTION

Before UV-Vis & IR exposure Bicotene® NEUTRALIZES the FR present in the skin. This situation could be comparable to normal daily exposure.

During the UV-Vis & IR exposure Bicotene® BLOCKS expected FR formation indicating its protection under intensive exposure to the sun.

* % with respect to native skin (in vitro)

Technique: ELETRON PARAMAGNETIC RESONANCE (EPR)

After UV-Vis & IR exposure Bicotene® improves skin RECOVERY suggesting its post solar protection.

BICOTENE® ANTIOX IR FR PROTECTION -

+ 68%

- 30%

Around 68% more FR were detected in the skin in vitro after IR irradiation, In samples treated with Bicotene® Antiox, less FR were generated during the irradiation. After IR irradiation Bicotene neutralised around 30% of the FR formed.

Bicotene neutralised around 45% of the excess of free radicals produced in the skin during IR irradiation.

Technique: ELETRON PARAMAGNETIC RESONANCE (EPR)

BICOTENE® ANTIOX UV-VIS FR PROTECTION

+ 48%

- 52%

Around 48% more FR were detected in the skin in vitro after UV-Vis irradiation. In samples treated with Bicotene® Antiox, less FR were generated during the irradiation. After UV-Vis irradiation Bicotene neutralised around 52% of the FR formed.

Bicotene neutralised 100% of the excess of free radicals produced in the skin during UV-Vis irradiation.

Technique: ELETRON PARAMAGNETIC RESONANCE (EPR)

BOOSTING SUNSCREEN FORMULATIONS

* % compared with native skin (in vitro)

Technique: ELETRON PARAMAGNETIC RESSONANCE (EPR)

Bicotene® was able to double the FR protection of a sunscreen SPF 50 + during UV exposure

BICOTENE® ANTIOX IN YOUR FORMULATION Stabilises carotenes and vitamins, being a source of stable antioxidants and Vit A precursors. Targets the deepest layers of the epidermis where the FR are mainly formed during solar exposure. Protects the collagen from the degradation induced by IR radiation, helping to avoid premature loss of skin elasticity and firmness. Provides the skin with free radical protection induced by UVVis or IR radiation. Protects the skin in different stages of sun exposure: BEFORE, neutralising FR present in the skin, DURING, by blocking the formation of FR and AFTER, by helping to restore the equilibrium. Boosts the free radical protection of sunscreens.

TECHNICAL INFORMATION Skin Care products Facial serums BB creams Moisturizing body lotions Detox creams Daily anti-pollution products Sun care products Sunscreens Post solar creams, lotions or gels Color cosmetics Make-up covers Lipsticks, etc.

CONCENTRATION OF USE: The recommended dosage of Bicotene® Complex is 2-3%. FORMULATION: Bicotene® is available in liquid or lyophilized forms. Both forms are compatible with creams, lotions, gels, serums and other skin care liquid or anhydrous formulations.

THANK YOU www.bicosome.com [email protected] T. (34) 93 400 61 63 c/ Jordi Girona 18 08034 Barcelona (Spain)