Science

Skincare Products with a Heart of Gold


Endor had developed a patented method of bonding hyaluronic acid to gold. The aggregate cluster is 22 nm in size and can easily penetrate the surface of skin. The extremely high density HA-coating triggers multiple CD44 receptors on keratinocytes, which stimulates the endogenous production of new elastin, hyaluronic acid, and the signal pathway that stimulate collagen remodeling by dermal fibroblasts. The gold is inert and harmless as that absorbed from jewelry and is sloughed out of skin between topical applications.

Hyaluronic Acid and Skin Hydration

Hyaluronic Acid (HA) is a very large molecule called glycosaminoglycan containing about 20,000 disaccharide monomers averaging 3 to 7 million Daltons in mass. These are highly negatively charged aggregates that imbibe tremendous amounts of water, and function to keep skin hydrated. One third of HA is degraded and synthesized each day.[1].  As we age the production of HA can drop to 5% of baseline!

HA is produced by keratinocytes in the epidermis and remains in skin and imbibes many time its weight of water to hydrate skin.  HA molecules, typically 3,000 nm in size, are too large to penetrate the intracellular space of 15 to 50 nm so remain trapped in skin. HA is what draws water from moisturizers into the skin.

Production of HA, Elastin and Collagen in Skin

The epidermis is the outer layer of skin made up mostly of cells called keratinocytes.  The keratinocytes have trigger sites on them called CD44 receptors that are sensitive to HA.  if multiple receptors are triggered they stimulate the production of endogenous hyaluronic acid and elastin, and signal other cells in the dermis called fibroblasts to produce collagen[2]. Hyaluronic acid plays a major role in wound healing, skin aging and repair.[7][9]

 

 

 

Use of Topical HA to Trigger Production of Elastin, and Collagen

Small fragments of HA, and nano-HA, can penetrate skin, however, they just as easily leave the skin so they provide the same short term hydration as pure water. HA receptors need a minimum molecular size to trigger multiple receptors[3][4], and because of electrostatic charge the small nano-HA molecules repell each other and cannot trigger multiple receptors on kerotinocytes.

Larger HA molecules can not penetrate the surface into the epidermis, and  HA that is applied topically will remain on the surface of skin and may actually pull water out and dehydrate skin!

The Endor Technologies® Solution

The solution is based on a patented method of bonding HA to 10 nm gold particles in a gold-HA complex called gold thioethylamino hyaluronic acid (AuHA™) . The highly charged part of the HA molecule bonds to the gold making the aggregate cluster very stealthy and about  22 nm in size so can easily penetrate the surface of the skin. The extremely high density HA coating triggers multiple CD44 receptors. The gold is sloughed from skin within 24 hours.

Safety

All Endor products contain AuHA™ approved in EU as a cosmetic ingredient and registered with the FDA for topical applications. Ceretox, a toxicological research center safety assessment report showed the use of the gold safe for cosmetic applications, based on toxicological profile, effect on gene expression (in vitro text at CSIC, skin absorption: Franz-cell test (IQAC lab-CSIC), Irritant potential, and patch test for human skin compatibility (Eurofins).   [5][6]

Results

Ultrasound imaging was used to evaluate the new collagen and hyaluronic acid production in the skin of 23 volunteers after 28 days of treatment.  The picture shows  AuHA has activated the production of new collagen and hyaluronic acid by 32% to 89% in the epidermis and 37% to 171% in the dermis.

Summary

The active ingredient in Endor products is AuHA, which is composed of  gold coated with 200 and 500 oligomer HA fragments of 5,000 to 10,000 daltons in size. At 22-nm total size they are smaller than any other HA-delivery system and can easily penetrate the surface of skin into the epidermis. A low concentration of AuHA has a very powerful effect activating  CD44 receptors on keratinocytes triggering the endogenous production of new HA, elastin, and collagen in skin.


[1] Stern R (2004). “Hyaluronan catabolism: a new metabolic pathway”. Eur. J. Cell Biol. 83 (7): 317–25.
[2] Ghatak S et el. (2015) “Roles of Proteoglycans and Glycosaminoglycans in Wound Healing and Fibrosis”. Int. J. Cell Biol. Article 834893, 20 pages.
[3] Cyphert et al  (2015). ”Size Matters: molecular Weight Specificity of Hyaluronic Effects in Cell Biology”. Int. J. Cell Biol. Article 563818, 8 pages.
[4] Ghazi et el. (2012). “Hyaluron Fragment Improve Wound Healing …”. Plus One. Vol 7, Issue 11, e48351.
[5] Guglielmoa C, et al. “Embryotoxicity of cobalt ferrite and gold nanoparticles: A first in vitro approach. Reproductive Toxicology 30 (2010) 271–276.
[6] Guglielmoa C, et al. “In Vitro Safety Toxicology Data for Evaluation of Gold Nanoparticles–Chronic Cytotoxicity, Genotoxicity and Uptake”. Journal of Nanoscience and Nanotechnology. Vol. 12, 6185–6191, 2012.
[7] Aya KL, Stern R. “Hyaluronan in wound healing: Rediscovering a major player”. Wound Rep Reg (2014) 22 579–593, 2014.
[8] Litwiniuk M, Krejner A, Grzela T. “Hyaluronic Acid in Inflammation and Tissue Regeneration”. Wounds 2016;28(3):78-88.
[9] Lilly Y.W. Bourguignon. “Matrix Hyaluronan-Activated CD44 Signaling Promotes Keratinocyte Activities and Improves Abnormal Epidermal Functions”. The American Journal of Pathology, Vol. 184, No. 7, July 2014


References

“Hyaluronic Acid: A key molecule in skin aging”. Papkonstantou E et el.DermoEndorcinology 4:3, 253-258 December 2012.

“Ultrastructural Analysis of Human Epidermal CD44 Reveals Preferential Distribution on Plasma Membrane Domains Facing the Hyaluronan-rich Matrix Pouches”. Anna-Liisa Tuhkanen, Markku Tammi, Alpo Pelttari, Ulla M. Ågren and Raija Tammi. J Histochem Cytochem 1998 46: 241.

“Identification of Hyaluronic Acid Binding Sites in the Extracellular Domain of CD44”.Robert J. Peach, Diane Hollenbaugh, Ivan Stamenkovic,  and Alejandro Aruffo. The Journal of Cell Biology, Volume 122, Number 1, July 1993 257-264.

“The High and Low Molecular Weight Forms of Hyaluronan Have Distinct Effects on CD44 Clustering”. Cuixia Yang et al. THE JOURNAL OF BIOLOGICAL CHEMISTRY VOL. 287, NO. 51, pp. 43094 –43107, December 14, 2012.

“Efficacy of a New Topical Nano-hyaluronic Acid in Humans”. S. Manjula Jegasothy, Valentina Zabolotniaia, and Stephan Bielfeldt. J Clin Aesthet Dermatol. 2014 Mar; 7(3): 27–29.

“Interaction of nanoparticles and cell-penetrating peptides with skin for transdermal drug delivery”. Pinaki Desai, Ram R. Patlolla, and Mandip Singh. Mol Membr Biol. 2010 Oct; 27(7): 247–259. doi: 10.3109/09687688.2010.522203.

Endor Technologies® and Endor® are a registered trademarks of Endor Technologies, Barcelona, Spain.
AuHA™ is a trademark of Perigee Bioscience.