Recent Updates in Cosmetic Technology

Dr. Khaled Al-QaoudR&D manager

Jordan Company For Antibody Production (MONOJO)

Personal Care

• ((For the first time, the world largest personal care market serving 500 million consumers will be served by a single, harmonized piece of legislations, directly applicable in all member states of the EU))

• Bertil heerink; director general of cosmetic Europe, July 2013.

Definition – Cosmetics

• Articles intended for:– Cleansing– Beautifying– Promoting attractiveness– Altering appearance

What are quantitative Ways for Its Effect

• Protection against sun radiation• Moisturization/hydration of the skin• Reduction of skin roughness• Reflection of light from the skin surface• Water loss changes• Effect on skin

– temperature– pH– Topography– Roughness– Friction

• Analysis of the cell layers of the stratum corneum and spinosum

Aging is a matter of skin Protein deformation

Elastin and Collagen proteins are main players

Major Concerns in Cosmetic Field

• Irritation• Allergic Reaction• Mutagenicity, cancer development

Safety First

• Cosmetics are principally concerned with FORM rather than FUNCTION.

• FORMULATION is a challenge• Every COMPONENT should complies with the

relevant regulations.• Deep understanding of problems linked to

release of active compounds on cutaneous level.

• What if SKIN is problematic

Animal Models For Skin Irritation and Topical Toxicity

• Guinea Pig Maximization Test (GPMT), The OECD Guidelines for the Testing of Chemicals guideline No. 406 of 1992

• Local Lymph Node Assay (LLNA), OECD Guidelines for the Testing of Chemicals guideline No. 429 of 23 July 2010

– first-choice method for in vivo testing

• Draize Rabbit Eye Test for predicting the ocular irritation/toxicity

• Mouse Ear Swelling Test

Skin Irritation Studies

MONJO Rabbit Ear Irritation Model

European Ban on Animal-Tested Cosmetics Finally Set for Implementation in March, 2013

What is banned in Europe related to animal use

• Testing of cosmetics on animals• sale of animal-tested cosmetics throughout the

EU from 2009• cosmetics-related animal testing• Imported cosmetics ingredients tested on

animals (2013)2013, India announced a ban on testing cosmetics on animals2014, Brazil followed

Animal Testing & CosmeticsFDA

• FDA is responsible for assuring that cosmetics are safe and properly labeled (Federal Food, Drug, and Cosmetic Act (FD&C Act))

• does not specifically require the use of animals in testing cosmetics for safety

• does not subject cosmetics to FDA premarket approval

• Agency advise cosmetic manufacturers to employ whatever testing is appropriate and effective for substantiating the safety of their products Including animal use

Animal Testing & Cosmetics• FDA supports and adheres to the provisions of

applicable laws, regulations, and policies governing animal testing, including the Animal Welfare Act and the Public Health Service Policy of Humane Care and Use of Laboratory Animals

• Maximum useful scientific information from the minimum number of animals

• consideration should be given to the use of scientifically valid alternative methods to whole-animal testing

• In 1997, FDA joined with thirteen other Federal agencies in forming the Interagency Coordinating Committee on the Validation of Alternative Methods (ICCVAM).

In vitro tests for skin sensitization

• Keratinocyte cultures• Langerhans cell cultures• Peripheral blood derived dendritic cells• Cell lines

Alternatives Non-Human-Animal testing

• Human 3D skin models• Monitoring DNA, RNA changes• Interleukins determination• Mutagenic testing on cell lines

Genotoxicity and Mutagenic Cosmetics

Chromosomaldamage due to toxic agent

Stain to visualize

Skin Hypersensitization

Cascade reaction for skin sensitization

Allergen study on human

skin

Skin Hypersensitization molecule level

good correlation between activation of the Nrf2 signaling pathway and chemical sensitization was first shown by Natsch and Emter (2008)

in vitro alternatives for safety testing

• European Centre for the Validation of Alternative Methods (ECVAM)

• In 2013, ECVAM recommended the DPRA for use in skin sensitization testing

• Direct Peptide Reactivity Assay (DPRA)• Covalent binding of electrophilic chemicals to nucleophilic

centres in skin proteins is often a key initiating event during the induction phase of skin sensitisation

• DPRA mimic this step by quantifying the reactivity of chemicals towards synthetic peptides containing either cysteine or lysine as reactive core

DPRA evaluation

EpiDerm™ is 3-dimensional Human Full Thickness Skin

• EpiDerm™ has been successfully utilized in alternative in vitro toxicology tests for dermal corrosivity, skin irritation, and phototoxicity

Stratum cornium

Epidermis

Dermis

A multi-endpoint, integrated testing approach that incorporates the following end points:• LDH to assess cytotoxicity• GSH depletion assay to assess direct reactivity• qPCR assays to detect up regulation of transcription of seven genes

involved in the Nrf2/Keap1/ARE or AhR/ARNT/XRE signalling pathways – NADPH-quinone oxidoreductase 1 (NQO1)– Aldoketoreductase 1C2 (AKR1C2)– Interleukin 8 (IL8)– Cytochrome P450 1A1 (CYP1A1)– Aldehyde dehydrogenase 3A1 (ALDH3A)– Heme-oxygenase 1 (HMOX1)– Glutamate cysteine ligase catalytic subunit C (GCLC)

SenCeeTox® Assay

NANOTECHNOLOGY and

COSMETICS

Current Reported Uses of Nanotechnology in Cosmetic Products

• Nanodispersed Systems– Liposomes (nanosomes)– Nanoemulsions– Solid lipid nanoparticles

• Other Nanoparticles– Polymer systems (nanocapsule, dendrimer)– Metal Oxide Nanoparticles

Nanodispersed Systems

Liposomes – lipid bilayer Nanoemulsion and lipid

nanoparticles – lipid monolayer Core can be hydrophilic or

hydrophobic depending on the number of phospholipid layers

Deliver water or lipid soluble ingredients1 c L i p i d n a n o p a r t i c l e : L ip id m o n o la y e r e n c lo s in g a s o l id l ip id c o r e

1 b N a n o e m u l s i o n : L ip id m o n o la y e r e n c lo s in g a l i q u id l i p i d c o r e

1 a L i p o s o m e : L ip id b i la y e r e n c lo s in g a n a q u e o u s c o r e

F i g u r e 1 : S t ru c t u r e o f n a n o d i s p e r s e d s y s t e m s

1 c L i p i d n a n o p a r t i c l e : L ip id m o n o la y e r e n c lo s in g a s o l id l ip id c o r e

1 b N a n o e m u l s i o n : L ip id m o n o la y e r e n c lo s in g a l i q u id l i p i d c o r e

1 a L i p o s o m e : L ip id b i la y e r e n c lo s in g a n a q u e o u s c o r e

F i g u r e 1 : S t ru c t u r e o f n a n o d i s p e r s e d s y s t e m s

Mufti, J.; Cernasov, D.; Macchio, R.; “New Technologies in Topical Delivery Systems” Happi.com, March 2002.

Cosmetic Nanoemulsions

• Nanoencapsulation of ingredients

• May be found in skin and hair care preparations

Useful in typical cosmetic formulations

Light or oxygen sensitive actives can be protected Vitamin A and Vitamin E

Low biotoxicity of phospholipid

US Patent 6335022; Simonnet; J._T., Sonneville; O., Legret; S.; L’Oreal, 1999.

Potential Lipid Nanoparticle Advantages

• Improved stability of ingredients• Controlled release of ingredients• Improved skin hydration• Incorporation of lipophilic ingredients• No or low carrier biotoxicity

• Uptake-Mainly insoluble particles• Should they become systemically

available, translocation/ transportation

• Accumulation in secondary target organs may occur

Consideration on Use of nanoparticles in Cosmetics

Scientific Committee on Consumer Products (SCCP-EU)-2007

Upper Hair Follicle

Image from: Tollet al., J. Invest. Dermatol. 123, 168-176, 2004.

Image shows penetration of microspheres into hair follicle. Authors concluded that penetration was between cuticula of hair shaft and inner root sheath

Laser scanning confocal microscopy (LSCM)

What Are Stem Cells

• Stem cells are unspecialized cells that have two defining properties– the ability to

differentiate into other cells

– the ability to self-regenerate

There are two types of stem cells, embryonic and adult.

Role of Stem Cells in Skin regeneration

• human skin is the largest depository of adult stem cells in the body.

• in the basic layer of the epidermis

• activated by tissue injury or disease.

Stem Cells in Cosmetics

U Autologous – self mesenchyme stem cell from abdomen fat---growth factors

there are no actual stem cells in any cosmetic products

Plant Stem CellsThe source are the meristematic tissues, which are located in:• root apical

meristem (RAM)• shoot apical

meristem (SAM)• and vascular

system ((pro)cambium or vascular meristem.

General Info

• Many stem cell cosmetics reside in a legal gray area• cosmetics do not require premarket approval from

the FDA- Is this applicable for Stem Cell cosmetics?• But stem cell cosmetics often satisfy the FDA's

definitions for both cosmetics and drugs• What manipulation to cells in lab, what cell product

is used, what is the source of stem cells???????

Regulatory

Summary

• Skin is Sensitive tissue• Safety first• Avoid using animal for testing• Look for alternative techniques that can be

adopted by authorities• Nanocosmetics have future in Market• The notable market potential for stem cell –

based cosmetics obliges mature legislations