Burn baby burn

Summer may be over in the northern hemisphere, but the damage that sunbathers have done to their skin will last a lifetime. Maria Burke explains how chemists are tackling the problem head on, with new sunscreens being developed to protect and possibly even repair damaged skin.

As winter approaches, we may dream of sunny summer days. But how many of us used our sunscreens properly, or at all, when out sunning ourselves? Although consumers are increasingly aware of the risks associated with sunlight, skin cancer numbers are growing faster in Europe than any other cancer. Worryingly, a report by UK consumer magazine Which? in June found that many sunscreens on the market do not give the promised protection levels, with some failing to meet industry standards. So just what is the industry doing to improve sunscreens?

The term sunscreen describes any material that protects the skin from UV radiation (UVR). There are three types of wavelengths in UVR. UV-B (280-320 nm range) can cause sunburn and is partially blocked by the earth’s ozone layer. UV-A (320-400 nm) penetrates the skin deeper than UV-B causing more long-term damage, such as premature ageing and skin cancer. UV-A can even penetrate windows and some clothes. It is not absorbed by the ozone layer. And finally there is UV-C, which is totally absorbed by the earth’s atmosphere.

Most sunscreens carry a SPF, or sun-protection factor, that indicates how long a user is protected from UV-B rays. A user can then determine how long the sunscreen is effective simply by multiplying the SPF by the length of time it takes for him or her to suffer a burn without sunscreen. However, the SPF system does not provide an objective measure of protection against UV-A radiation. Some sunscreens also carry a star rating, which is defined as the UV-A:UV-B absorbance ratio per unit wavelength.

Active sunscreen components are based on organic molecules, inorganic nanoparticles or a combination of the two. Organic, or chemical, sunscreens contain relatively complex molecules that absorb into the skin, but most only block UV-B. They work primarily by absorbing UV light and dissipating it as heat, and include para amino benzoic acid, octyl methoxycinnamate, 4-methylbenzylidene camphor, avobenzone, oxybenzone, and homosalate.

About half the chemical sunscreens sold end up in cosmetics like foundation and lipstick.

Inorganic, or physical, sunscreens are mainly zinc oxide or titanium dioxide (TiO₂), formulated as ultrafine (20-50 nm) particles. They work primarily by reflecting and scattering UV light. However, TiO₂ only protects against UV-B and short wave UV-A, not long wave UV-A. Zinc oxide, however, protects against UV-B, and short and long-wave UV-A, making it a ’broad spectrum’ sunscreen.

For the next generation of products, the industry is mainly focusing on developing broad spectrum active ingredients that provide consistent protection across all wavelengths, particularly in the UV-A range, says Sebastian Marx of the European Cosmetic, Toiletry and Perfumery Association (Colipa). ’Currently, there are absorption minima that have to be countered by mixing and blending different actives,’ he explains and adds that companies are also responding to consumer interest in all-day UV protection as an anti-ageing issue. Another important goal is to develop simple in vitro tests to show the efficacy of UV-A and UV-B actives.

There is a growing recognition that people need to protect themselves against UV-A, as well as UV-B, if they are to reduce the risks of skin cancer and ageing, explains Kevin Matthews, chief executive officer of Oxonica, a nanomaterials company based in Oxford, UK. ’Part of the clear message now is that UV-B protection will reduce risks of one skin cancer type, but will not reduce risk of two others: basal cell carcinoma and melanoma.’

While UV-B chemical sunscreens have been used for years, UV-A chemical sunscreens are a relatively recent occurrence. The US Food and Drug Administration has approved effective chemical UV-A sunscreens agents within the past 18 months, including butyl methoxydibenzoylmethane. Unfortunately, this material is difficult to use in formulation and can react with other ingredients.

Hampered by product instability and the loss of efficacy, the quest to create chemical sunscreens offering both UV-A and UV-B protection hasn’t been an easy one. Companies are experimenting with different techniques, such as US-based Englehard Corporation’s process that combines butyl methoxydibenzoylmethane with ethylhexyl methoxycinnamate.

Oxonica has another solution to the problem of providing UV-A protection in a stable product. The reason why sunscreen agents don’t last forever is mainly because some chemical components are either degraded by light over time, or are affected by other UV-sensitive components, says Matthews. ’There is evidence to suggest that TiO₂ can enhance the degradation of chemical sunscreen agents, including UV-A chemical sunscreens, for example avobenzone. Coating TiO₂ may help, but it’s not invariably effective.’

Oxonica has developed a UV absorber, which, it says, offers better and longer-lasting protection against UV-A as well as other benefits. Based on TiO₂ doped with manganese, it is extremely photostable. ’Indeed, it is possible to provide all day protection sunscreens by incorporating the doped materials,’ says Matthews. Optisol is stable for three to four hours giving five-star protection - around 90 per cent of all UV-A and UV-B wavelengths - whereas the conventional sunscreens they tested fell to three-star in less than two hours, he reports.

Optisol has another advantage. Most UV absorbers used in sunscreens can form free radicals that are implicated in skin ageing and cell damage, and manufacturers add anti-oxidants to try and neutralise them, Matthews explains. However, Optisol absorbs UVR without forming free radicals. ’The manganese molecules sit within the TiO₂ lattice and prevent electrons from migrating to form free radicals. Other Mn molecules sit on the surface where they mop up any free radicals that are generated,’ says Matthews.

Apart from developing broader spectrum products to protect against a wider range of wavelengths, the other main trend in sunscreen development is to find products that feel better, are easier to apply and have a ’natural’ appearance. ’These characteristics mean consumers are more likely to use sunscreens more effectively,’ says Dan Yarosh, chief executive officer of AGI Dermatics, a dermatology-based company in New York State, US. ’If people applied sunscreens properly, it would cut skin cancer rates by 80 per cent.’

Many of the large manufacturers are also working on these more cosmetic issues. One drawback with physical sunscreens is that they may leave white streaks or blobs on the skin. Generally, the oil in a sunscreen formula helps wet the inorganic particles and gives the optical effect of transparency, but this doesn’t always work well when sunscreens contain high levels of TiO₂.

Companies are taking different approaches to this problem. UK company Uniqema, for example, has developed a product range containing TiO₂ with a particle size distribution between 40 and 50 nm. It claims this provides good UV protection and avoids the large particles that produce whitening effects. Elsewhere, Engelhard favours adding a red interference pigment - mica coated with TiO₂ - which it claims counteracts whitening effects.

Meanwhile, natural products have become a dynamic new segment of the personal care market in many countries. Natural sunscreens offer innovative new research lines for companies jostling for position in a crowded marketplace. However, Colipa’s Marx warns overlooking the environmental consequences of widespread extraction of natural ingredients has many dangers and thinks promising substances may well end up being synthesised to avoid damage to natural habitats.

In Israel, Claes Enk’s research group at the Hebrew University and the Hadassah Medical Center is working with pigments isolated from ancient microorganisms, such as lichens and cyanobacteria. So far, they have patented two molecules with UV-B protective qualities, and identified two plant-derived UV-A absorbing pigments.

These ancient plants depend on solar irradiation as their primary energy source, explains Enk, and they have developed various protective mechanisms to allow them to survive under direct UV radiation. One trick is to synthesise UV-absorbing compounds such as scytonemin (a lipid soluble compound), mycosporine and mycosporine-like amino acids (MAAs).

Enks’ team has shown in laboratory studies and in human experiments that these compounds are at least as effective as conventional sunscreens in protecting against sunburn, as well as against DNA damage. And even more promising, says Enk, are the UV-A absorbing compounds that provided five-star UV-A protection. The conventional sunscreens they were tested against only scored three stars. But it may be a few more years before any of these molecules are turned into products.

Researchers from the Australian Institute of Marine Science (AIMS) are investigating compounds used by reef-building corals living in shallow tropical waters to withstand long-term exposure to high levels of potentially damaging solar radiation. These corals also have to cope with possible damage from oxygen produced by photosynthesising algae living within their tissues.

The AIMS team, led by Walter Dunlap, has established that many marine organisms produce, or accumulate from their diet, MAAs as a way of protecting themselves against this radiation. MAAs are simple, non-aromatic chromophores with a high efficiency to absorb UV light and an ability to protect cells from structural and physiological UV damage. To date, about 25 structurally distinct MMAs have been identified, although research suggests that there are many still to be characterised.

The researchers first tried to prepare simple derivatives of the functional chromophore. While they succeeded in reproducing the sunscreen characteristics, their simplified analogues were unstable for commercial use, explains Dunlap. But they did manage to stabilise some chromophores and synthesise structural derivatives of others, which are being tested for sunscreen acceptability.

MAAs are also the focus of work being undertaken by researchers at Plymouth Marine Applications, the commercial arm of Plymouth Marine Laboratory (PML) in the UK. But they derive their MAAs from microscopic algae, or phytoplankton, which float on the sea’s surface because they need the sun to photosynthesise.

’Because phytoplankton live in the surface of the sea they are at risk from the sun’s damaging UV rays,’ said Carole Llewellyn, a marine chemist at PML. ’These tiny plants have evolved over millions of years and have found a variety of ways to protect themselves, including the production of compounds that block out UV light.’

These MAAs absorb UV radiation very strongly between 310-370 nm, Llewellyn reports. This ability to absorb mainly in the UV-A range makes them particularly attractive as a potential commercial product because there is a gap in the market for UV-A screens at present and UK-based Boots, which is keen to develop natural products, is sponsoring the project.

The Plymouth researchers are screening and analysing a whole range of microalgae to find those that produce MAAs with the most market potential. MAA levels vary across species and are different for each MAA, explains Llewellyn. It is possible, she says, that although MAAs may be present in phytoplankton cells, the ability to produce significant amounts through photo-induction may be limited to certain species.

While sunscreens at present simply absorb or reflect UV photons at the skin surface, Barbara Gilchrest of the Boston University School of Medicine, US, predicts that the next generation of sunscreens is likely to include agents that work directly with skin cells to protect against UVR. ’Recent progress in understanding the skin’s own defence systems, for example, tanning and enhanced DNA repair capacity, should allow for this step forward,’ she says.

In March of this year, Gilchrest, working with David Goukassian, reported the first study showing that a DNA fragment called pTT increases the ability of skin cells to repair UV-induced DNA damage in skin, in the long-term as well as short-term. Significantly, they found that this enhanced repair capability makes cells less vulnerable to future UV exposures as well.

When DNA absorbs UV energy, adjacent DNA bases can link together to form ’photoproducts’, the most common of which are thymine dimers, explains Gilchrest. Photoproducts can lead to mutations during DNA synthesis. She continues: ’the enzyme responsible for replicating the DNA cannot "read" the code accurately and can insert the wrong base in the new DNA strand. This often causes the DNA to give rise to an abnormal protein that cannot function properly. UV-induced mutations in genes that encode cell cycle regulatory proteins are ultimately responsible for UV-induced skin cancer.’

The researchers applied pTT - two thymidine bases linked by phosphate groups - to the skin of hairless mice. They found that treated cells were able to repair the photoproducts faster than control cells. This should mean fewer mutations and skin cancers.

pTT works by making cells produce more of a protein called p53 and it also activates this protein. Gilchrest: ’[p53] causes the cell to make more DNA repair proteins and otherwise stimulates the cell machinery that repairs damage and prevents future damage. We believe that pTT mimics a normal physiologic signal in cells following DNA damage and thus tricks cells into believing they have been damaged, when they have not.’

As for the future, Gilchrest believes that ’at some level, pTT treatment could be seen as helpful and appropriate for all individuals exposed to UV’. The Boston team would very much like to see pTT available for patients, but no clinical trials are planned at present. Boston University has licensed the patents to SemaCo, a small start-up company that is now seeking a larger commercial partner.

Mark Birch-Machin of the University of Newcastle upon Tyne, UK, is also investigating DNA damage. He has developed a test that can show DNA damage to skin over time. The test, which has a patent pending, gives a direct measurement of a sunscreen’s (or its components) DNA protection ability in human skin cells. Birch-Machin hopes to form ’in the very near future’ a new company called DNAcare Systems, which will offer a unique service to enable companies to have their products rated for their ability to protect the skin from DNA damage. ’Using our unique sunburnt DNA technology, we will be able to tell companies how good their existing sunscreens are in terms of DNA protection,’ he explains.

But Birch-Machin aims to go one step further and use this technology to formulate a specifically designed sunscreen to provide better protection against DNA damage than anything else on the market. ’Current sunscreens are tested based on their ability to protect against sunburn,’ he says. ’However, it is well-known that DNA damage in the skin occurs well before sunburn begins.’ He is in early stage discussions with several major cosmetic companies to create the sunscreen.

Medical research into DNA damage and skin cancers could prove useful for the wider population in the long term as Dan Yarosh, chief executive officer of US company Applied Genetics (AGI) Dermatics, believes. AGI Dermatics is developing a drug that delivers a DNA repair enzyme into skin cells where it helps repair UV damage. Phase III trials of the drug in patients with a genetic skin disorder (in which sufferers are hypersensitive to sunlight and develop skin cancers at an early age) are very promising. But Yarosh hopes its application will be much broader. Trials are planned for patients who have had one skin cancer, or pre-malignant cancer. ’These individuals - about 10 million in the US alone - are at high risk of developing cancer again,’ he explains. ’We think this product would protect them.’ In the long-term, a similar product could be used in a daily skin cream for children or in after-sun products to protect against UV damage, says Yarosh.

The hope is that future sunscreens will contain materials, whether synthetic or natural, that will protect against the whole range of UV wavelengths.They will work on several levels, preventing superficial sunburn while also protecting the DNA inside our cells. ’Although in the past the demand was for products that prevented sunburn, in the future, the demand will be for UV-A protection and for cell protection against UV-induced damage,’ says Hansj?rgen Driller, head of cosmetic actives at Merck KGaA in Germany. ’Sunscreens in the future will have to consist of a photostable absorption system, based on organic as well as inorganic UV-filters, accompanied by active ingredients, which could stabilise the self protection system of our skin.’

As our understanding of the science behind sunburn, skin cancer and skin ageing advances, it looks likely that sunscreens will move more into the realm of healthcare. So we may find we use them everyday as part of a daily health regimen, not only in the long, hot days of summer.

Acknowledgements

Maria Burke is a freelance science writer based in St Albans, Hertfordshire, UK