Developing Skin-Lightening Products

Developing Skin-Lightening Products

Skin lightening refers to the ability of a product to reduce hyper-pigmented areas or spots on the skin. These products, also referred to as skin-whiteners, brighteners, or bleach creams, try to even and lessen skin coloration due to the formation of excessive melanin.

The Biology of Skin Pigmentation

The skin pigmentation process is complex. It’s believed there are at least 14 primary mechanisms involved in the formation of skin color, as well as 3 secondary ones. Skin color originates in the epidermis, where the pigment-producing cells, melanocytes, are located.

Upon UV exposure, these cells produce pigment, called melanin. This process is referred to as melanogenesis (see figure below-right) and is controlled by the copper-containing enzyme tyrosinase. Tyrosinase is located in vesicles called melanosomes which are inside melanocytes.

Two types of pigments are synthesized in melanosomes: eumelanin and pheomelanin. Eumelanin is a dark brown-black insoluble polymer, and pheomelanin is a light red-yellow sulphur containing soluble polymer.

M. Gillbro, M. J. Olsson, The melanogenesis and mechanisms of skin-lightening agents – existing and new approaches. Int. J. Cosmet. Sci. 2011, 33, 210-221. Click to view full size image.

Most skin-lighteners (EU) target tyrosinase inhibition as the main mechanism. New actives have been developed that claim to interfere with the transfer of melanosomes to keratinocytes. Another efficient mechanism would be to block the up-regulation of tyrosinase and block the stimulation of melanocyte dendricity. This could be achieved by interfering with the binding of keratinocyte mediators to their melanocyte receptors or by inhibiting the production of these mediators.

Skin-Lightening Strategies

Skin-lightening strategies include utilizing combinations of materials that work by different mechanisms. All skin-lightening formulations should contain a chelating agent (EU), an antioxidant (EU), and a skin-soothing agent (EU).

Enzyme Inhibition

• Tyrosinase synthesis and activity.
• Phenylalanine hydroxylase (PAH).
• Tyrosinase hydroxylase isoenzyme 1 (TH-I).
• Dopa oxidase
• Tyrosinase-related proteins (TRP-1,2) similar to tyrosinase.
• Antioxidant enzymes such as catalase, glutathione peroxidase, glutathione reductase and thioredoxin reductase.
• Protease-activated receptor 2 (PAR-2) inhibition may have an impact on melanosome transfer.
• Binding to the peroxisome proliferator activated receptor-gamma (PPAR-gamma) and thereby inhibiting the mRNA and protein levels.

Other Mechanisms

• Inhibit melanocyte dendricity.
• Inhibit melanin stimulating hormone (MSH).
• Melanosome transfer inhibitors.
• Reduce skin irritation, which is known to stimulate hyperpigmentation.
• Inhibit microphthalmia-associated transcription factor gene (MITF) expression. MITF plays a central role in melanin synthesis, as well as melanosome biogenesis and transport.
• Increase cell turnover and desquamation.
• Chelating agents – copper (EU) is essential for tyrosinase activity. Utilize antioxidants. UV irradiation can produce reactive oxygen species (ROS) in the skin that may induce melano-genesis by activating tyrosinase.
• Utilize cosmetic anti-inflammatory agents (EU).
• Serine protease inhibitors may also inhibit Melanosome transfer.

Recommended Ingredients

Niacinamide
May inhibit melanosome transfer.

ALPHA-ARBUTIN  ­

Tested at 1%, it was shown to perform better than 1% hydroquinone after 1 month.

Ascorbic Acid

Suppresses melanin formation.

Retinol/Retynyl Palmitate
Inhibits tyrosinase, TRP-1.

Oligopeptide-68

A novel skin-lightening active that inhibits tyrosinase, MITF, TRP-1, and TRP-2. MITF is a critical factor in melanogenesis.

TGP2

Decrease melanin synthesis by down-regulation of TRP-1, TRP-2, MITF, and Tyrosinase, - Block Melanosome transfer form Melanocyte to Keratinocyte.  
Glycolic/lactic acids
Increase cell turnover/desquamation and may inhibit tyrosinase.

Fragrance Compounds
Several fragrance compounds may be useful in skin-lightening products. Developing a fragrance designed for skin-lightening products could be useful to increase efficacy. The following have significant tyrosinase inhibition at 100ug/ml:

• Citronellic acid-89%
• Citronellol-75%
• Geraniol-66%
• Farnesol-57% (EU)
• Decanol-57%
• Tetrahydro geraniol

Reference
J. M. Gillbro, M. J. Olsson, The melanogenesis and mechanisms of skin-lightening agents – existing and new approaches. Int. J.  Cosmet. Sci. 2011, 33, 210-221.