Paolo Giacomoni, PhD, Insight Analysis Consulting09.01.21
Perhaps the most widespread misconception in the field of skin care is that the skin is a barrier. The skin is the interface between the body and the outside world; it releases in the environment fluids such as carbon dioxide, sebum and sweat. It takes up from the environment gases like oxygen. It conveys information about the environment such as temperature, wind and tactile feelings. It processes foreign molecules to achieve immune responses...and it is prone to penetration.
Nature and Nurture
“Penetration”—the word that raises eyebrows in the offices of the FDA! And yet, many a xenobiotic do naturally penetrate the epidermis. Methyl-nicotinate, used as a rubefacient in OTC products, does indeed penetrate and provoke vasodilation. When applied after exposure to UV radiation, nicotinamide boosts DNA repair, restores the production of energy as well as the immune response. Urushiol, the toxin found in poison ivy, does penetrate, gets oxidized, binds to endogenous proteins and elicits sensitization. Many other molecules, harmful or beneficial, do penetrate the epidermis.
However, many molecules that could be beneficial to the skin in one way or another do not spontaneously penetrate the epidermis. Water is one, and the skin care industry has generated technologies to convey water in the stratum corneum to increase its hydration. These light-texture products have remarkable moisturizing effects. One such technology was developed around 1985 by Rosemary Hadjani-Vila, then with L’Oréal. It consists of water entrapped in lipid vesicles called niosomes.1 Niosomes are a modification of the lipid vesicles called Bangham liposomes.2 Instead of being composed of phospholipids, they are made with nonionic surfactants, hence the name.
Vehiculating Xenobiotics Via Vesicles
Bangham liposomes were used in the 1970s and early 1980s to transfer foreign molecules into cultured cells. The success of niosomes and their feasibility on the industrial scale triggered further research into the preparation of vesicles to convey not only water but also beneficial xenobiotics to the lower layers of the epidermis. The next step was the preparation of nano-capsules of vitamin E3 that were shown by histology analysis to penetrate in the lower layers of human epidermis. When applied before exposure to ultraviolet radiation, they succeed in maintaining the morphology of the epidermis that otherwise would become spongiotic.4
It was later shown that larger molecules and enzymes can be vehiculated across the epidermis in appropriate vesicles. Because of the harmful effect of DNA-damaging UV-irradiation, Daniel Yarosh endeavored fostering the penetration of DNA repair enzymes, and succeeded.
The enzyme T4 endonuclease V is an enzyme that cuts the DNA, performing an incision where there is a UV-induced damage and triggers the repair process. Humans who cannot accomplish the incision step because of a genetic defect called Xeroderma pigmentosum develop skin cancer and have shorter lifespan. Photolyase is an enzyme able to bind to UV-induced DNA damage and, upon irradiation with blue light, can “undo” the damage and restore DNA to its pristine state. Vehiculating T4endonucleaseV or photolyase in the epidermis could be beneficial for people who accumulate DNA damage after excessive exposure to ultraviolet radiation.
T4endonucleaseV in lipid vesicles was topically applied to the skin of volunteers after exposure to UV and was detected in the lower layers of the epidermis by immuno-gold staining.5 Photolyase encapsulated in vesicles called photosomes was applied to the skin of human volunteers after exposure to UV radiation and DNA damage levels were assessed in skin biopsies. When the application of photolyase was followed by exposure to blue light, the level of DNA damage was dramatically less than in the UV-irradiated control.6
Droplette Technology
The science behind the preparation and the loading of the vesicles is well established. The difficulty in preparing formulas for transepidermal delivery is a technological one. The physical requirements of the industrial preparation of the formula (temperature, surfactants, etc) may be incompatible with the stability of the xenobiotic to be vehiculated.
A new technology seems to have succeeded in overcoming these difficulties.
Instead of preparing bulks of xenobiotic-containing vesicles and then formulating them in a cream, the Droplette technology avoids the problem by assembling the ingredients in a “regular” cream that is then “nebulized” by a piezo-electric device and expelled by a pump, both comprised in the cream-containing jar. The piezo-electric device makes the droplet size just one micrometer; i.e., 100 times smaller than the width of a single hair. The pump accelerates the aerosol, further reduces the droplet size and expels microdroplets at a high velocity into the skin.
According to Droplette, ingredients work, but topical formulas often don’t work. It’s a viewpoint shared by many a cosmetic chemist! Droplette’s scientists are keeping dermatologist-approved ingredients as the final structure of the micro-mist and are just changing the “packaging” around them to obtain tiny and fast droplets that break through the skin. The ingredients administered via the Droplette technology are of various sizes, and said to penetrate about 20 layers of the epidermis. That is to say that they cross the stratum corneum and reach suprabasal layers, perhaps reaching down to the stratum basale.
We wait impatiently for the results of the analysis of their penetration and of their efficacy, as it was performed for niosomes, nanocapsules, T4 endonucleaseV and photosomes.
References
Paolo Giacomoni, PhD
Insight Analysis Consulting
paologiac@gmail.com
516-769-6904
Paolo Giacomoni acts as an independent consultant to the skin care industry. He served as executive director of research at Estée Lauder and was head of the department of biology with L’Oréal. He has built a record of achievements through research on DNA damage and metabolic impairment induced by UV radiation as well as on the positive effects of vitamins and antioxidants. He has authored more than 100 peer-reviewed publications and has more than 20 patents.
Nature and Nurture
“Penetration”—the word that raises eyebrows in the offices of the FDA! And yet, many a xenobiotic do naturally penetrate the epidermis. Methyl-nicotinate, used as a rubefacient in OTC products, does indeed penetrate and provoke vasodilation. When applied after exposure to UV radiation, nicotinamide boosts DNA repair, restores the production of energy as well as the immune response. Urushiol, the toxin found in poison ivy, does penetrate, gets oxidized, binds to endogenous proteins and elicits sensitization. Many other molecules, harmful or beneficial, do penetrate the epidermis.
However, many molecules that could be beneficial to the skin in one way or another do not spontaneously penetrate the epidermis. Water is one, and the skin care industry has generated technologies to convey water in the stratum corneum to increase its hydration. These light-texture products have remarkable moisturizing effects. One such technology was developed around 1985 by Rosemary Hadjani-Vila, then with L’Oréal. It consists of water entrapped in lipid vesicles called niosomes.1 Niosomes are a modification of the lipid vesicles called Bangham liposomes.2 Instead of being composed of phospholipids, they are made with nonionic surfactants, hence the name.
Vehiculating Xenobiotics Via Vesicles
Bangham liposomes were used in the 1970s and early 1980s to transfer foreign molecules into cultured cells. The success of niosomes and their feasibility on the industrial scale triggered further research into the preparation of vesicles to convey not only water but also beneficial xenobiotics to the lower layers of the epidermis. The next step was the preparation of nano-capsules of vitamin E3 that were shown by histology analysis to penetrate in the lower layers of human epidermis. When applied before exposure to ultraviolet radiation, they succeed in maintaining the morphology of the epidermis that otherwise would become spongiotic.4
It was later shown that larger molecules and enzymes can be vehiculated across the epidermis in appropriate vesicles. Because of the harmful effect of DNA-damaging UV-irradiation, Daniel Yarosh endeavored fostering the penetration of DNA repair enzymes, and succeeded.
The enzyme T4 endonuclease V is an enzyme that cuts the DNA, performing an incision where there is a UV-induced damage and triggers the repair process. Humans who cannot accomplish the incision step because of a genetic defect called Xeroderma pigmentosum develop skin cancer and have shorter lifespan. Photolyase is an enzyme able to bind to UV-induced DNA damage and, upon irradiation with blue light, can “undo” the damage and restore DNA to its pristine state. Vehiculating T4endonucleaseV or photolyase in the epidermis could be beneficial for people who accumulate DNA damage after excessive exposure to ultraviolet radiation.
T4endonucleaseV in lipid vesicles was topically applied to the skin of volunteers after exposure to UV and was detected in the lower layers of the epidermis by immuno-gold staining.5 Photolyase encapsulated in vesicles called photosomes was applied to the skin of human volunteers after exposure to UV radiation and DNA damage levels were assessed in skin biopsies. When the application of photolyase was followed by exposure to blue light, the level of DNA damage was dramatically less than in the UV-irradiated control.6
Droplette Technology
The science behind the preparation and the loading of the vesicles is well established. The difficulty in preparing formulas for transepidermal delivery is a technological one. The physical requirements of the industrial preparation of the formula (temperature, surfactants, etc) may be incompatible with the stability of the xenobiotic to be vehiculated.
A new technology seems to have succeeded in overcoming these difficulties.
Instead of preparing bulks of xenobiotic-containing vesicles and then formulating them in a cream, the Droplette technology avoids the problem by assembling the ingredients in a “regular” cream that is then “nebulized” by a piezo-electric device and expelled by a pump, both comprised in the cream-containing jar. The piezo-electric device makes the droplet size just one micrometer; i.e., 100 times smaller than the width of a single hair. The pump accelerates the aerosol, further reduces the droplet size and expels microdroplets at a high velocity into the skin.
According to Droplette, ingredients work, but topical formulas often don’t work. It’s a viewpoint shared by many a cosmetic chemist! Droplette’s scientists are keeping dermatologist-approved ingredients as the final structure of the micro-mist and are just changing the “packaging” around them to obtain tiny and fast droplets that break through the skin. The ingredients administered via the Droplette technology are of various sizes, and said to penetrate about 20 layers of the epidermis. That is to say that they cross the stratum corneum and reach suprabasal layers, perhaps reaching down to the stratum basale.
We wait impatiently for the results of the analysis of their penetration and of their efficacy, as it was performed for niosomes, nanocapsules, T4 endonucleaseV and photosomes.
References
- Handjani-Vila R et al (1989) Cosmetic and pharmaceutical compositions containing niosomes and a water-soluble polyamide, and a process for preparing these compositions. US Patent US 4830857A 16th May, 1989
- Bangham AD, Hill MW, Miller NG. (1974) Preparation and use of liposomes as models of biological membranes. In: Korn ED, editor. Methods in Membrane Biology. Vol. 1. New York: Plenum. pp. 1–68.
- Fessi H et al (1992) Procédé de préparation de systèmes colloïdaux dispersibles d’une substance, sous forme de nanocapsules. European Patent No 0274961, 25 March, 1992
- Giacomoni PU et al (1998) Morphological alterations and Cell Blebbing in UV-irradiated human epidermis. Arch Dermatol Res 290 : 163-166
- Wolf P et al (2000) Topical Treatment with Liposomes containing T4 Endonuclease V protects Human Skin in vivo from UV induced upregulation of IL-10 and TNF-α. J Invest Dermatol 114 : 149-156
- Stege H, et al. (2000) Enzyme plus light therapy to repair DNA damage in ultraviolet-B-irradiated human skin. Proc Natl Acad Sci. 97 : 1790–1795.
Paolo Giacomoni, PhD
Insight Analysis Consulting
paologiac@gmail.com
516-769-6904
Paolo Giacomoni acts as an independent consultant to the skin care industry. He served as executive director of research at Estée Lauder and was head of the department of biology with L’Oréal. He has built a record of achievements through research on DNA damage and metabolic impairment induced by UV radiation as well as on the positive effects of vitamins and antioxidants. He has authored more than 100 peer-reviewed publications and has more than 20 patents.