We are hearing the term Nanotechnology used more frequently in marketing of skin care products, and while the term sounds like it belongs in robotics and science fiction, it is rapidly becoming a reality in medicine and skin care. Currently, there are approximately three new products incorporating Nanotechnologies being released per week across the heath and beauty sectors, with over 360 products going to market since 2005.
As few people really understand what the technology is, its benefits or what the potential implications of its use are, we decided to create this overview.

The type of Nanotechnology that is most significant in the beauty, skin care and health sectors is the use of nanoparticles (Or buckyballs as they are known in the industry), and it is a specific type of these Nanoparticles that have been touted as the next generation of Liposomes.
Nanosomes are one of the most recognised names for the nanoparticles used in skin care and cosmetic products, and we are also familiar with the term liposome, so this similarity between the two is the perhaps the best way to explain what Nanosomes are.

Liposome 101
We know Liposomes are microscopic, fluid-filled spheres whose walls are made of layers of phospholipids analogous to the phospholipids that make up cell membranes in our skin.
Liposomes can be custom designed for almost any need by varying the lipid content, size, surface charge and method of preparation, making them suitable for delivery systems for drugs, vitamins and cosmetic materials.
Active ingredients are encapsulated in the Liposomes, and as mentioned, the liposome wall is very similar, physiologically, to the material of cell membranes. When the active solution entrapped within Liposomes is applied to the skin, the Liposomes begin to combine
with the cellular membranes. In the process, the Liposomes release their payload of active materials into the cells. As a consequence, not only is delivery of the actives very specific: directly into the intended cells; but the delivery takes place over a longer period of time.

The disadvantage with conventional large, liposomes (Typically 1 micron in size) are that they are actually liposomes within liposomes, and have a limited ability to penetrate narrow blood vessels or into the skin to a significant degree. Consequently, some of the materials that are entrapped in the inner layers of these liposomes may in certain conditions be virtually un-releasable.

Introducing Nanosomes
Nanosomes (or nanoparticles) are very small, single or double bilayer Liposomes that are so small they are measured in the Nanometer range, (Hence the name)and are approximately 800 times smaller (Typically 50 Nanometers in size) than the diameter of the human hair. Nanosomes can be up to twenty times smaller than liposomes,
dependant on type, and these tiny, liposomes differ from their larger brothers in both composition and manufacturing process.
Nanosomes are composed from much higher quality phospholipids ingredients than the commercial lecithin that larger liposomes are created from, some with higher percentages of phosphatidylcholine (PC), one of the essential components of cell membranes.
Lecithin, a commonly used source for Liposomes typically contains only 10-20% phosphatidylcholine, however higher grades used to create Nanosomes may contain up to 40% phosphatidylcholine. Because the higher-grade materials that make up the Nanosomes
are believed to possess more mammalian molecular characteristics than conventional Liposomes, they possess greater non- antigenic properties and are more biodegradable.

Some of the processes to create Nanosomes include the use of high-pressure Supercritical fluids or subjecting large, multiple-layer liposomes to ultrasonic

energy. These processes are complex, lengthy, and extremely delicate. Consequently, the cost to produce Nanosomes is more expensive than conventional liposomes.

Advantages
Since Nanosomes made with various phospholipid types can contain, encapsulate, and mobilise both water soluble materials as well as oil soluble materials, not only can they deliver a wide variety of encapsulated ingredients to cells, but in the cases of higher grades of materials, also deliver phosphatidylcholine (PC), to help feed the cells' own building block.

The PC phospholipid molecule is a universal building block for cell membranes, and the cell's membranes are its essence: they regulate the vast majority of the activities that make up life. This unique ability of high purity PC Nanosomes is claimed to render them potentially one of the most powerful available tools in combating cellular aging.
Due to such small size, (the interstices of the outer layer of skin measure about 100 nanometers), Nanosomes can more easily penetrate into the skin by topical application, with their active ingredients entrapped inside them more efficiently transported and delivered to desired target cells.

Nanoparticle concerns
Nanosomes allow the delivery of active ingredients, vitamins and even sun protection compounds to lower levels of the skin, and it is these contents of the Nanosomes, which are creating concerns in some factions.
In 2005, concerns were raised by both the UKs Royal Society (Britains most prestigious scientific body) and the Food and Drug Administration (FDA) in the United States regarding what effect the minute particles may have if they enter cells in the human body or leach into the bloodstream, and called for for a comprehensive programme of research, and potentially a trialling and licensing system be introduced for hi-tech cosmetics similar to that used for pharmaceuticals.
In a recent report, the Royal Society stressed that because nanoparticles often have their own chemical properties, they should be treated as new chemicals under both UK and European legislation, in an effort to initiate appropriate safety testing and labelling.
(It recommends that any products containing nanoparticles be labelled as such)
The Societies concern is that manufacturers ensure that the toxicologal tests that they use recognise that nanoparticles of a given chemical will often have different properties to the same chemical in its larger form and may have greater toxicity.

Biochemists at the University of Calgary in Canada claim to have concluded from research conducted with high-powered computing resources running cell behaviour simulations that nanoparticles are able to dissolve in animal cell membranes, pass into cells and re-form particles on the other side where they have the potential to cause damage to the cells.
Nanotechnology, which was originally employed in man-made fibres and pharmaceuticals, has also been derided by some perhaps over cautious public identities, and has in some circles provoked similar fears to those sparked by genetic modification, although no harmful effects have yet been proved.

In the United states, an organisation called The Project on Emerging Nanotechnologies (PEN) stated that funding on Nanotechnology risk research in the US is lacking, and believe that more should be spent to clarify public perceptions about risks - real and perceived.

Despite organisations such as the Royal Society and the FDA stating that very little is known about the interaction of nano-scale particles and the skin, and what the long-term effects might be in the bloodstream, cosmetic giants globally believe the future of skin care and anti-ageing products lies with nanotechnology and is investing millions of dollars annually in the development of new delivery systems. The LOral company currently owns over two dozen patents on nanosome particles alone.
Industry experts see the use of Nanotechnology and the incorporation of nanoparticles into skin care formulations as an area of immense potential for a category that continues to witness some of the largest annual sales growth.

With all new technologies there will always be concerns over the impact or effect it will have on the user, with Nanotechnology and Nanosomes no different.
With increased ability to physiologically alter the skin cells with these new technologies, the old question whether a treatment or product is cosmetic or therepeutic raises its ugly head once more.

2008 Virtual Beauty Corp

Researched By Ralph Hill

Despite being banned for use in skin treatment products in over a dozen western and African countries, Hydroquinone is still used in the US and Canada for de-pigmentation (skin lightening) in formulations with concentrations of 2% over the counter and up to 4% by prescription.
Why is it still prescribed when it has largely been abandoned elsewhere due to reported adverse effects and detrimental health warnings?

Almost every skin treatment practitioner knows of Hydroquinone. Many have at one time used products containing it, but many may not know enough about this compound to make an informed judgement on its safe use.
The fact that its use as a skin-lightening agent is banned in so many countries raises questions of its suitability in current cross-ethnic society.
Hydroquinone is still considered to be the gold standard of treatment for hyperpigmentation by many physicians in the US and Canada, this despite its abandonment elsewhere.
So exactly what is Hydroquinone? What effects does it have on our cells and systems, and why has it been banned in some countries?

What is Hydroquinone?
It is an aromatic organic compound which is a type of phenol. It is also known as alpha-hydroquinone, hydroquinol, quinol, benzoquinol, p-benzenediol, 1,4-benzenediol, p-dihydroxybenzene, p-hydroxyphenol, p-dioxobenzene, 1,4-dihydroxybenzene, dihydroquinone, pyrogentistic acid, quinnone, aida, arctuvin, eldoquin, eldopaque, phiaquin, tecquinol, tenox HQ, tequinol.
 

Typical industrial uses include Corrosion Inhibitors, Photochemical developers, Printing and process regulators during the manufacturing of polystyrene and latex products.
In human medicine, hydroquinone has been used since the 1930s as a topical application to selectively de-pigment or reduce the color of skin.
It is currently classified as a poison, and is listed on CAS (US) and MSDS (UK) chemical databases as possible carcinogen, severe skin irritant, and allergen, and was given Alert status by World Health Organization IPCS (International Programme on Chemical safety) in 1996.

How does Hydroquinone work? 
Hydroquinone produces reversible depigmentation of the skin of humans by a complex mechanism of action. 
At the cellular level, hydroquinone and its derivatives are oxidized by tyrosinase to form highly toxic free radicals that cause selective damage to the lipoprotein membranes of the melanocyte, thereby reducing conversion of tyrosine to dopa and subsequently to melanin. It disrupts membranous cytoplasmic organelles, affecting formation, melanization, and degradation of melanosomes.

Typical topical preparations of 2 - 5% hydroquinone have been proven effective in producing cutaneous depigmentation, although the 2% concentration is considered by many as safer while producing results equal to higher concentrations.
Long-term observation would suggest hydroquinone offers better results on lighter skins and on lighter lesions. In skins with higher melanin density, the response to hydroquinone depends on the amount of pigment present. The earlier it is used to treat minor skin blemishes, the more likely the results will be satisfactory.
On commencement of treatment, melanin excretion may briefly increase and when depigmentation does occur, melanin production is reduced by approximately 50%.

A decrease in skin colour usually becomes noticeable in approximately 4 weeks; however, the time of onset can vary from 3 weeks to 3 months.
Typically, depigmentation lasts for 2 - 6 months, but is reversible. Darker lesions generally re-pigment faster than lighter lesions, and ethnically darker skins (Fitzpatrick types 5 & 6) will re-pigment more readily due to the dendrites of the melanocyte being longer and reaching further in to the upper layers of the epidermis (Through and often above the granular layer) than lighter skins.
Because the ability of the sun to darken lesions is much greater than that of hydroquinone to lighten them, strict avoidance of sunlight during its use is critically important.

What can go wrong?
Typical side effects of topical hydroquinone are generally mild when used in low concentrations, however tingling or burning on application and subsequent erythema and inflammation can occur in over 30% of users with higher occurrences in formulations approaching a 5% concentration.
As well as frequently irritating the skin, these concentrations if used for prolonged periods can cause disfiguring effects including epidermal thickening, weak connective tissue, ochronosis-like pigmentation (a bluish black discoloration of tissue) and yellowish papules. The mechanism for the formation of the rare ochronosis-like pigments on the skin is thought to occur by the inhibition of hydroquinone on the epidermal homogentisic acid oxidase. This inhibition would lead to the accumulation of homogentisic acid, which then polymerises to form the ochronotic pigments.

In darker skins, it is reported that exogenous ochronosis is more widespread with prolonged use. This disorder is characterized by progressive darkening of the treated area. Histologically, the degeneration of collagen and elastic fibres has occurred.

This degeneration is followed by the appearance of characteristic ochronotic deposits consisting of crescent-shaped, ochre-coloured fibres in the dermis.
It is these issues with darker skins that have forced many health authorities in countries with darker skin populations to take steps to limit the sale of, or ban the sale of hydroquinone for use on the skin. This however did not solve the problem as since the banning of the ingredient, the sales of products that contain hydroquinone have, to a large extent, been driven underground. Traders are known to supply these creams from under the counter and consumers are continuing to buy these products unwittingly.
In 1999, a South African epidemic of exogenous ochronosis due to black market hydroquinone products was reported more than a decade after they were banned for having disfigured thousands of darker skinned women.

Other concerns
Hydroquinone is known to irritate some skin and to make all skin more sensitive to sunlight, and by making the skin sensitive to the sun, hydroquinone can quickly render it more vulnerable to the very problems the chemicals are meant to get rid of when used incorrectly.

This along with consumers' concerns over those side effects and over reports that the chemical may be connected to more serious health problems in laboratory animal tests (Hydroquinone has been reported to induce mutations in Salmonella and at the hart locus of Chinese hamster V79 cells) have led many cosmetics companies to avoid using it in their skin lightening products.

Several respected scientists have written papers regarding the carcinogenic potential of hydroquinone, with one document from the European Academy of Dermatology & Venereology summarising with this: The risks of long-term effects (cancer) of topically applied hydroquinone may no longer be ignored. Based on recent evidence of the potential risks, which are higher than has been assumed up until now, we plead that the use of hydroquinone as a skin lightening agent will be stopped completely.

In 1997, the Swedish National Chemicals Inspectorate issued a paper concerning the Carcinogenicity and Mutagenicity of Hydroquinone, and discussed the classification of the compound as a class 2 mutagen and class 2 carceogen after hyperploid spermatocytes were observed in a number of in vivo studies conducted at the Rome Laboratory of Comparative Toxicology and Ecotoxicology. These studies were part of a coordinated research program sponsored by the Commission of the European Communities in to ten known and suspect spindle poisons. (These poisons disrupt cellular reproduction by affecting the protein threads that connect the centromere regions of chromosomes, known as spindles)

Interestingly, in the US and Canada where Hydroquinone is still sold and used in concentrations of up to 4%, there does not seem to be such concern.
In a US publication, Critical Reviews in Toxicology, May 1999, research indicated reactions are minor or a result of using extremely high concentrations. A leading professor of dermatology at a US university school of medicine was reported to have stated: To date there is no evidence of adverse systemic reactions following the use of hydroquinone", and "hydroquinone is undoubtedly the most active and safest skin-depigmenting substance... ."
With such polarised opinion on the use of Hydroquinone, it is easy to understand why there is such confusion.

Hydroquinone prohibition
Because of the potential mutagenic and carcinogenic properties that produce mid-term effects such as leukomelanoderma , along with ongoing problems with darker skins, France and most of Europe banned cosmetic creams or treatments containing hydroquinone in 1999, with the UK, Australia and New Zealand following in 2001. As mentioned previously, South Africa banned its use as early as 1989, with other African countries such as Kenya and Uganda enforcing bans in 1998.
The UK has taken the ban one step further by making it illegal to supply, offer to supply or posess to supply. This is due to the embarrassment of the discovery that British companies were smuggling their contraband hydroquinone creams and lotions to agents in South Africa, Zimbabwe, Zambia, Angola, Zaire, Botswana and Kenya. In those countries where skin bleaching using hydroquinone was popular, reports of severe adverse effects including individuals with such bad skin disease that they are unable to safely go out in the sun, and doctors experiencing cases in which they cannot apply stitches to the skin because it has weakened to the point where it falls apart. 
Lack of control or guidance of use caused many of the problems associated with hypopigmentation and ochronosis. Users of skin lightening products who misused the formulations in an effort to get a faster result unwittingly hastened the ban. The only exception to the bans on hydroquinone are its use in hair dyes, where in most countries products are permitted to contain a maximum level of 0.3%. This is over five times less than the levels typically found in skin lightening creams sold on the internet and in the US and Canada.

Alternatives
While alternative ingredients may not provide the quick fix depigmentation that hydroquinone offers, there are other options that may sit easier on your concience for treatment of pigmentation issues. 

Kojic Acid is perhaps the most recognized and purportedly effective alternative to hydroquinone. It is derived from a variety of different fungi and organic substances (such as soy and mushrooms) and works the same way as hydroquinone by inhibiting melanin production. It is known to cause contact allergies in a minority of case.

Azelaic Acid is another popular alternative found naturally in wheat, rye, and barley. It is saturated dicarboxylic acid with antibacterial properties that also lends itself to the treatment of acne. In treating pigmentation, it is less effective as a tyrosinase inhibitor, and when used in conjunction with other ingredients its role is that of an exfoliant, helping desquamate the pigmented keratinocytes in the treatment area.

Arbutin is another efficient tyrosinase inhibitor. It is a glycosylated benzoquinone extracted from the bearberry plant. Because it is a hydroquinone derivative it can have similar melanin-inhibiting properties. When used in conjunction with Aloesin, (a C-glycosylated chromone compound isolated from aloe ) the combination provides an effective modulation of melanogenesis.

Paper Mulberry is also a tyrosinase inhibitor isolated from a plant herbal extract. In one study, a comparison of the tyrosinase inhibition of a paper mulberry/ kojic acid mixture revealed similar results to that of hydroquinone without significant irritation after 24 hours.

Glabridin (liquorice extract) has been reported to inhibit tyrosinase activity of melanocytes without cytotoxicity, and has showed promise treating UV-Binduced pigmentation and erythema with topical applications of just 0.5% glabridin. The anti-inflammatory properties of glabridin are attributed to inhibition of superoxide anion production and cyclooxygenase activity.

© 2006 Virtual Beauty Corporation

References:

Michael P Tabibian, MD, Consulting Staff, Department of Dermatology, Daniel Freedman Hospital, Marina Hospital

Craig G Burkhart, MD, MPH, Clinical Professor, Department of Medicine, Section of Dermatology, Medical College of Ohio at Toledo, Clinical Assistant Professor, Department of Dermatology, Ohio University School of Medicine

Mutagenesis. 1992 Jan;7(1):69-76. Miller BM, Adler ID.

Associate Professor Mohd Isa Abdul Majid Ph.D

Skin Lightening and Depigmenting Agents. Alaina J James, MD, PhD, Staff Physician, Department of Dermatology, University of Pennsylvania Medical Center

Journal of the European Academy of Dermatology and Venereology, December 2004

Toxicology and health risks of hydroquinone in skin lightening formulations. TJ Kooyers, W Westerhof

Johannesburg Sunday Times, 12 December 1999

The Village Voice, January 23 - 29, 2002

CNN.com/World of August 14, 2001

Of the many unusual (from a traditional perspective) chemicals finding their way in to modern cosmetics and skin care are fluorinated oils. A quick search regarding the development and uses of these specialty oils finds us looking at synthetic fluids commonly associated with air-conditioning. So how do oils used in such a dissimilar industry to beauty find its way in to cosmetics and skin care?

To understand why fluorinated oils are used in cosmetics we need to look at the properties of these oils. There are different types of fluorinated oils and the specific type of this article is the perfluorinated oils or perfluorocarbons (PFCs)
Perfluorinated oils are essentially silicone based fluids with oil like properties. One of the types of fluorinated oil used in cosmetics was patented by Daikin industries (Japanese Air-conditioning giant) who use PFCs in refrigeration as an alternative to CFCs. It was developed primarily due to its low temperature properties and (Fluorinated oils do not change viscosity at temperature extremes) higher density than water.
Perfluorocarbons are more importantly an inert and non-flammable alternative to Hydrocarbon oils.

These key properties of being inert, having no smell and colour, non-flammable, non-corrosive, low viscosity and hydrocarbon free along with low toxicity and short retention time in the body also makes them a good candidate for cosmetics, particularly in the use of make-up and skin care.

Fluorinated oils and other materials such as silicones obtain their properties by treatment with Fluorine: the most chemically reactive and electronegative of all the elements. Fluorine's large electronegativity and small atomic radius gives it remarkable bonding characteristics, particularly in conjunction with carbon.
Flourines properties are most recognised in the production of low friction plastics such as Teflon, (non-stick surfaces) and in halons such as Freon. (airconditioning fluids)

In cosmetics, fluorine-modified oil and silicone derivatives exhibit high water- and oil-repellency to provide cosmetics, which wear, long (increasing usable daily life span) and have a good feel on use.

Some powders used in cosmetics are also flourine treated, and the use of the fluorinated oils solve the oil repellency problems encountered with non-flouronated oils such as vegatable and mineral oils. Flouronated oils also exhibit low water absorption properties, another desirable feature for an oil in make-up.

One of the more interesting fluorinated oils is perfluorodecalin. This high purity perfluorocarbon is chemically and biologically inert, and its ability to dissolve (or physically carry) gases, (and more specifically oxygen) makes it especialy useful in medical and skin care applications.
PFD can in fact, dissolve large amounts of oxygen, (100 ml of perfluorodecalin at 25C will dissolve 49 ml of oxygen under certain conditions) and this property has seen it used in a wide variety of applications from an artificial blood called Fluosol to a component of storage mediums for organs and tissues for transplant.

Oxygenated perfluorocarbons administered in emulsions are known to increase surface oxygen concentration but without the need for a pressure chamber. Consequently, they are extremely useful for repair of scar tissue, leg ulcers and radiation burns. The same effect has been used to grow cell cultures.

As a development of the medical applications, perfluorodecalin is now used as an ingredient in several cosmetic and skin care products, where its ability to dissolve and carry gasses such as oxygen is belived to revitalise skin and help reduce wrinkles.
It is also lipophobic and hydrophobic forming a third phase which facilitates emulsion formulation.

Typical concentrations range between 5 20% depending on the type of formualtion, and it can be found in a wide variety of products including face & neck creams & gels, eye contour products, oxygen masks, and hair care. (Where its non-greasy and ability to prevent sebum build up is useful as a detangling agent)

Beneficial claims
As with many compounds and chemicals used in skin care products, the claims of what miraculous feats can be achieved is often driven by the marketers imagination and not the science.
There have been claims that some formulations containing as little as 6% perfluorodecalin can increase oxygen pressure in the skin by 100%. In one particular advertising statement, there is a claim that Perfluorodecalin delivers Pure Oxygen for rapid cell function. There are references to clinical trails and studies, however no specific details are provided.
In another brands marketing information, references are made to Perfluorodecalins role in gasotransportation, along with ensuring the 'aeration' of skincells. In another product, perfluorodecalin was listed in the ingredients as being a oxygen substitute. If all of this is factual, then Perfluorodecalin is indeed a highly benificial ingredient. However.....

While it is easy to get quite enthusiastic about Perfluorodecalin because of its medical successes as an artificial blood, we must understand that it does not actually contain any oxygen in its molecular structure. (it comprises of 10 Carbon atoms and 17 Flourine atoms)
Perfluorodecalin can indeed move oxygen, and this is facilitated by a process known as passive diffusion.
Passive diffusion takes advantage of gasses' affinity to move from areas of greater concentration to areas lesser concentration until it reaches a state of equilibrium.
In the human body, oxygen moves from the lungs (high concentration) to the blood (low concentration). Then, once the blood reaches the capillaries, the oxygen moves from the blood (high concentration) to the tissues (low concentration). The claims of the skin care marketers imply that the oxygen is taken or transported from the atmosphere (high concentration) and delivered through the bilayer membrane to lower levels of the epidermis. (Low concentration) This happens to a certain degree due to the passive diffusion characteristics of the oil, however while it is true that perfluorodecalin does indeed dissolve gases,(one of it's benificial properties) these gasses include carbon dioxide and nitrogen, so unless the perfluorodecalin in the formula is already fully saturated with oxygen, (or being applied in a pure oxygen envirionment) there are the obvious questions on how can it deliver pure oxygen to the skin surface.
The reality is of course, that due to the laws of physics, Perfluorodecalin can not transport or deliver more oxygen than it is surrounded by. Perhaps a little creative pseudoscience is employed by some skin care marketers?
Whatever the claims, Perfluorodecalin in skin care formulations does indeed have beneficial properties, but perhaps not so earth shattering and efficient as some assert. Research continues.

Other perfluorocarbons
Other variations typically used in cosmetics as skin conditioners, hair de-tanglers, solvents etc include: Perfluoromethylcyclopentane, Perfluoroperhydrophenanthrene, Perfluoro-1,3-dimethylcyclohexane, Perfluoromethyldecalin, and Perfluoroperhydrobenzyltetralin.

Typical perfluorocarbon properties

• Odourless, colourless, non-volatile, low viscosity liquids
• Non-sensitising, Non-irritant Non-greasy
• Refreshes and smoothes the skin
• Enhances the appearance of tacky and sticky final products
• Can be used in colour products for enhanced colour endurance
• Creates a third phase emulsion and acts as a co-emulsifier
• Creates a thin film application with basic water proofing properties
• Creates transient gel structure
• Does not interfere with the normal function of the skin

Negative aspects
PFCs are recognised as extremely potent greenhouse gases, and they are a long-term problem with a lifetime up to 50,000 years.
PFCs are one of the classes of compounds regulated in the Kyoto Protocol.(The United Nations Framework Convention on Climate Change)
Most of the PFCs creating the greenhouse warming potential however, are from industrial use such as aluminium smelters.
The vow volume use in skin care and medical applications have no reported effect on the environment to date.

2008 Virtual Beauty Corporation