Update on photoprotection.

Photoprotection by sunscreens, clothing and glasses are important to protect the skin against the detrimental effects of sun exposure. In order to achieve complete protection, topical strategies must shield against the range of solar wavelengths ultraviolet A, ultraviolet B, infrared radiation that can damage the skin. To provide the necessary broad spectrum coverage, combinations of chemical and physical UV filters along with molecules that are capable of interfering with and/or preventing the deleterious effects of sunlight are discussed in this review.

Introduction

Ultraviolet (UV) composes only a small region of the electromagnetic radiation spectrum and is divided into three subdivisions: Ultraviolet C (UVC) (200–290 nm), Ultraviolet B (UVB) (290–320 nm), and UVA (320–400 nm). Ultraviolet A (UVA) is further divided into UVA1 (340–400 nm) and UVA2 (320–340 nm). Ozone in the Earth's atmosphere absorbs 100% of UVC, approximately 90% of UVB, and virtually no UVA and hence depletion of the ozone layer has lead to a substantial increase in UV transmission to the Earth's surface.

The understanding of Ultraviolet radiation (UVR) and its effects on the skin is important. The UV spectrum causes ageing of the skin, sunburn development, the production of precancerous and cancerous lesions, and immunosuppression. Immunosuppressive effects include suppression of contact hypersensitivity and delayed-type hypersensitivity and changes in Langerhans cell function.[1] UVA is associated with ageing effects and produces pigmentation. It penetrates deeper into the skin layer and indirectly damages the DNA via the production of radical oxygen species (ROS). It causes a decrease in Langerhans cells present in the dermis, whereas increasing inflammatory cells in the dermis.[2] UVA increases the expression of p53, a tumor suppressor gene,[3] whereas promoting UVB carcinogenicity and oxidative stress.[4] UVB exposure, on the other hand, causes sunburns and DNA strand breaks. UVB produces pyrimidine dimer mutations, which are strongly associated with nonmelanoma skin cancers.[4]

For many years the focus of research and protective strategies, has been centered on the UV part of sunlight, because their relatively high photon energy causes macroscopic skin changes that are visible even after a short duration of exposure resulting in accelerated skin ageing and contributing to the development of cancer. UV radiation only accounts for approximately 7% of the sun's energy[5] but Infrared A (IRA) (760–1440 nm) can also act as a damaging environmental factor to skin through its ability to result in alterations in gene expression of skin cells at multiple points,[6] resulting in accelerated skin ageing[78] and contributing to the development of cancer.[9]

The effect of visible light on the skin has received very little attention, compared with UV radiation and its effects on the skin are probably less important than the role of UV radiation. However, visible light sensitivity is an important phenomenon in diseases such as porphyria, solar urticaria, and other idiopathic photodermatoses such as polymorphous light eruption.

Photoprotection

Modern topical photoprotection involves both primary protective factors (sunscreens) that absorb or reflect UV radiation and secondary factors (e.g., antioxidants, osmolytes, and DNA repair enzymes) that can disrupt the photochemical cascade triggered by UV-penetration, thereby limiting skin damage.

Sunscreens

Sunscreens have been divided into chemical absorbers (organic) and physical blockers (inorganic) on the basis of their mechanism of action. Chemical sunscreens are generally aromatic compounds conjugated with a carbonyl group. This general structure allows the molecule to absorb high-energy UV rays and release the energy as lower-energy rays, thereby preventing the skin-damaging UV rays from reaching the skin. Physical blockers or nonchemical sunscreens reflect or scatter UVR. They contain inert minerals such as titanium dioxide or zinc oxide. Organic are either UVA or UVB blockers [Table 1].

Table 1

Sunscreens and their absorption spectra

UV B blockers

Aminobenzoates

Padimate O is the most potent UV-B absorber. The decline in its use, along with the demand for higher sun protection factor (SPF) products have led to the incorporation of multiple active ingredients into a single product to achieve the desired SPF, replacing single Para amino benzoic acid (PABA) esters.

Cinnamates

The cinnamates have largely replaced PABA derivatives as the next most potent UVB absorbers. They are octinoxate (octyl methoxycinnamate [OMC]) and cinoxate (2-ethoxyethyl-methoxycinnamate). OMC is a potent UVB absorber and is the most frequently used sunscreen ingredient. The efficacy of OMC can be further increased when encapsulated in polymethyl methacrylate microsphere.[10]

Salicylates

Salicylates are weak UVB absorbers and they are generally used in combination with other UV filters. Both octisalate and homosalate are water insoluble that leads to their high substantivity, which is the ability to retain its effectiveness after exposure to water and perspiration. Trolamine salicylate is water soluble and has been used in hair products. These compounds can also play a minor role to stabilize and prevent photodegradation of other sunscreen ingredients.[11]

Octocrylene

The absorption profile of octocrylene spans from 290 to 360 nm with peak absorption at 307 nm. The compound has an excellent safety profile with low irritation, phototoxicity, and photoallergic potential.[12] Octocrylene may be used in combination with other UV absorbers to achieve higher SPF formulas and to add stability.

Ensulizole

Ensulizole or phenylbenzimidazole sulfonic acid is water soluble, and it is used in products formulated to feel lighter and less oily, such as daily use cosmetic moisturizers. It is a selective UVB filter, allowing almost all UVA transmission.

Ultraviolet A

Benzophenones

Although benzophenones are primarily UVB absorbers, oxybenzone absorbs well through UVA II and can be considered a broad-spectrum absorber. It significantly augments UVB protection when used in a given formula. Oxybenzone has the highest incidence of contact and photocontact dermatitis of all sunscreens, and these reactions are intensified by exposure to sun or heat.[13]

Benzophenones have poor substantivity, but uptake of the molecules is detectable in the blood and urine after topical application. However, the systemic absorption seems to be of little biological consequence.[14] The molecules become unstable with UV exposure via oxidation reactions and consumption of antioxidant reserves.[11]

Oxybenzone is not photostable and can generate oxygen radicals upon UV exposure.[15] There is a concern about its endocrine and carcinogenic effect even though current scientific studies have not supported this fears.[16]

Anthranilates

Anthranilates are weak UVB filters, and they absorb mainly in the near UVA portion of the spectrum. Anthranilates are less effective in this range than benzophenones, and they are less widely used.

Avobenzone

Butyl methoxydibenzoylmethane or avobenzone provides superior protection through a large portion of the UVA range, including UVA I. Despite its efficacy and broad spectrum, avobenzone is intrinsically photounstable and significant photodegradation can occur with a loss of 50–90% of molecules after 1 hour of UV exposure.[17] To increase the photostability of avobenzone, molecules such as UV absorber (e.g., octocrylene) and non-UV filter (e.g., diethylhexyl 2, 6-napththalate) are added.

Ecamsule

Terephthalylidene dicamphor sulfonic acid or Mexoryl SX provides protection within the near UVA range. The compound is photostable, water resistant, and has low systemic absorption.

Methylene-bis-benzotriazolyl tetramethylbutylphenol (MBBT)

It is a broad spectrum sunscreen, decreasing UVA more than UVB transmission. This molecule offers a broad spectrum coverage with two absorption peaks at 303 and 360 nm. The molecule size is large, minimizing the opportunity for systemic absorption or endocrine-like effects. It acts as a hybrid between organic and inorganic filters, combining the micronized particle technology of inorganic UV filters with an organic molecule and together, these properties serve to absorb, scatter, and reflect UVR.

Bis-ethylhexyloxyphenol methoxyphenyl triazine (BEMT)

It has a broad spectrum of coverage from 280 to 380 nm and is photostable. It is also advantageous for a lack of endocrine-like effects.[18]

Hydroxybenzotriazoles class: Drometriazole trisiloxane

Drometriazole trisiloxane (DTB) belongs to the class of hydroxybenzotriazole molecules. It has broad-spectrum coverage and is photostable.

Inorganic sunscreens

Inorganic sunscreens or physical blockersscatter or reflect UV rays

Some of the original sunblocks were opaque formulations reflecting or scattering UVR. Poor cosmetic acceptance had limited the widespread use until micro sized forms became available, also known as inorganic particulate sunscreens.

Titanium dioxide

Titanium dioxide is a broad-spectrum UV filter that does not penetrate the stratum corneum. It has undergone a process of micronization for improved cosmesis. Microfine titanium dioxide provides photoprotection against UVB and UVA II (315–340 nm)[18] but lacks coverage within UVA1 (340–400 nm).

Zinc oxide

Zinc oxide is a safe and effective ingredient in photoprotective products. It is photostable, nonphotoreactive,[19] and nonphotocatalytic.[12] It has little potential for irritation or sensitization. Smaller, micronized zinc oxide is considered as a broad-spectrum UV protectant. Although not as efficient in the UVB range as titanium dioxide, this inorganic UV filter covers predominately the UVA spectra, with protection into UVA1. Zinc oxide is also considered inferior as a UV filter to the organic sunscreens.[12]

Secondary photoprotection

Secondary photoprotection involves the use of active agents to counteract the inherent photochemical processes that can induce DNA damage in skin cells. It may be achieved by antioxidants, osmolytes, and DNA repair enzymes,[2021] (e.g., photolyase and T4 endonuclease V).

UVA damages the skin tissue through reactive oxygen species (ROS) production, and these radicals are neutralized by the body's innate defense mechanism through a series of enzymatic (e.g., superoxide dismutase, catalase, glutathione reductase, and peroxidase) and nonenzymatic antioxidants (AOs). When the buildup of ROS from UV and environmental pollutions exhausts the enzymatic machinery and depletes the AOs reservoir, damage to the DNA, lipid membrane, and proteins can occur. Topical AOs exert their effect inside the cells and can reverse this shortage. Furthermore, once penetrated through the stratum corneum, they may remain active for several days.[22] The antioxidants have also been shown to protect against Near infrared radiation (IRA) and hence they are important for their central role in IRA induced adverse effects .[723]

Antioxidants that are used in sunscreens and cosmetic products are vitamins and polyphenols. Vitamins formulated in sunscreens are water soluble vitamin C and lipophilic vitamin E. Application of L-ascorbic acid has shown to protect UV-related damage as measured by erythema or sun burn cells.[24] Topical application of α-tocopherol has demonstrated a number of protective effects including reduction in erythema,[25] photoaging,[26] photocarcinogenesis,[26] and immunosuppression.[27]

Silymarin

Silymarin is derived from the milk thistle plant, Silybum marianum. This flavonoid has strong AO effects capable of scavenging ROS and preventing lipid and lipoprotein oxidation. Topical silymarin has been shown to inhibit UVB-induced sunburn cells, prevent UVB induced pyrimidine dimers, and reduce the number of UVB-induced tumors in mice.[28]

Green tea polyphenols

Green tea contains a rich level of polyphenols and as AOs, tea polyphenols are more potent than vitamins C and E. They are capable of scavenging singlet oxygen, superoxide radicals, hydroxyl radicals, peroxyl radicals, and hydrogen peroxide. Aside from the AO functions, tea polyphenols also have antiinflammatory and anticarcinogenic effects.[29]

Osmolytes

Osmolytes are small molecules that control and stabilize the cellular environment by regulating hydration and responses to stress conditions. Osmolytes (compatible organic solutes) are not only utilized by cells to control cell volumes, but they have been identified as integral parts of the cellular defense against environmental noxae. The osmolytes taurine[30] and ectoine[31] have been demonstrated to protect against detrimental UV effects and are incorporated into several commercially available sunscreens.

Photoprotection by clothing

Wearing clothing has been emphasized as an important means of photoprotection. Compared with sunscreens, clothing has a number of advantages. Clothing and hats offer a balanced and uniformed protection for both UVA and UVB but most of the sunscreens deliver more UVB protection. Clothing and hats offer more reliable protection as long as users remember to wear them. By contrast, a user needs to apply sunscreens 30 minutes prior going outdoors and reapply them every 2 hours, and the degree of protection offered by sunscreens depends on application of the correct amount of the product.

The protection offered by clothing is measured by ultraviolet protection factor (UPF).

UPF is defined as the ratio of average effective UV irradiance transmitted without fabric to the average effective UV irradiance transmitted through fabric. Fabrics are placed into classes based on the calculated label UPF value.[32] The good protection is composed of fabrics with label UPF value of 15–24, the very good protection class is composed of fabrics with label UPF values of 40–50, and 50+ (the highest value permitted on a label).

Polyester has the best UV absorbing capacity while cotton has the least.[33] The use of optical whitening agents can likewise increase UPF through their fluorescent-like properties (re-emitting absorbed UVR in the visible spectrum); however, this augmented protection is limited by partial UVB coverage.[34]

To conclude wearing a colored loose fitting fabric offers the best photoprotection from clothing.

Photoprotection by glasses

UVR filtration by sunglasses is important because it prevents the development of certain ocular disorders including cancers of the eye/eyelid, cataracts, and possibly age-related macular degeneration. Sunglass effectiveness, on the other hand, depends on factors such as size, shape, UV blocking ability, and reflection from the back of the lens.[13] The American Academy of Ophthalmology recommends that sunglasses block 99% of UVR, and those that comply with this standard are labeled accordingly.[35] The United States, the United Kingdom, Germany, Australia, and France have standards for UV protective sunglasses. In our country we do not have any standard guidelines for sunglasses. Dongre et al.[36] studied the UV protective properties of sunglasses in UV phototherapy chambers and reported that the mean reduction in UVA penetration was 84.89% and that in UVB penetration was 68.74%. Thirteen sunglasses (four branded ones and nine unbranded ones) provided greater than 80% reduction in UVA rays and hence wearing sunglasses during outdoor work could provide adequate sun protection.

Newer technologies in sunscreens

Various technologies are used to make the sunscreens more effective and cosmetically acceptable.

Nanotechnology in sunscreens

Nanomaterials are ultrafine single particles with a diameter less than 100 nm.[37] Nanotechnology is currently being developed for diagnosis and labeling, targeting of drugs, and immunotherapy. In 1999 the Food and Drug Administration (FDA) allowed the use of nanoparticles in sunscreens. The use of nanoparticles improves the texture and cosmetic appeal of sunscreens.

The traditionally used physical blockers such as titanium dioxide and zinc oxide are thicker formulations and hence were not cosmetically acceptable. The newer sunscreens containing nanosized products of titanium dioxide and zinc oxidehave replaced the older formulations and these ultra fine particles blend with the skin and are cosmetically acceptable.

The use of nanotechnology has revolutionized the field of sunscreens but toxicologists believe that the nanoparticles can be potentially harmful. The penetration of nanoparticles are limited by their molecular size. Lademann et al.[38] investigated the penetration of titanium dioxide microparticles into the horny layer and the orifice of the hair follicle in human skin and found that the amount of titanium dioxide found in any given follicle was less than 1% of the applied total amount of sunscreen. Penetration of microparticles into the viable skin tissue was not detected.

The larger surface area of the ultrafine particles can provide an interface for catalytic reactions which can produce free radicals and damages the proteins, lipids and DNA. Nanoparticles can also form complexes with proteins which can escape immunological surveillance.[39] The nanoparticle–protein complexes can also act as haptens, which can induce autoimmune diseases.[40] Further studies are required to determine the safety of nanosized particle sunscreens.

Sunspheres

This technology consists of styrene/acrylate polymers that form a nonabsorbable material. These spheres are then filled with water, which upon application to the skin, escapes leaving a hollow shell capable of light scattering.

These hollow spheres increase the surface area contact of UV filters with incoming UVR, increasing the effective SPF of a sunscreen by 50–70%.

Controversial aspects of sunscreens

There are certain controversies regarding the usage of sunscreens

Schulmpf et al.[41] noted that benzophenone, 3-benzylidene camphor, 4-methylbenzylidene camphor, and octyl-methoxycinnamate increased uterine weight in immature rats. Scientific Committee of Cosmetic Products and Non-Food Products, an European committee based in Belgium, noted that the relative estrogenic potencies of UV sunscreen products, both in vitro and in vivo, were about 1 million less than estradiol, the positive control substance.[11] Thyroid weight was increased by higher 4-methylbenzylidene camphor doses. The UV filter benzophenone 2 inactivates human recombinant thyroperoxidase in vitro and disturbs thyroid hormone homeostasis in rats.[42] The endocrine activity of sunscreens is controversial and future studies are warranted.

There are conflicting reports regarding the efficacy of sunscreens against the immunosuppressive effects of UV and it has been shown that the application of a sunscreen with a higher SPF can decrease the systemic UVB induced suppression of contact hypersensitivity in human skin.[43]

Regular sunscreen application can delay[44] or prevent the onset of skin tumors in mice, while other reports also indicate its efficacy against precancerous human lesions.[45] There is also a risk that the regular use of sunscreen could lead to decreased vitamin D levels in the elderly[46] through the decreased UVB-induced cutaneous synthesis of previtamin D3; but the risk is minimal in tropical climate.

Measuring sunscreen efficacy

The UVB protection offered by sunscreens is measured by the SPF and substanstivity.

Sun protection factor

SPF is a numerical rating system to indicate the degree of protection provided by a sun care product. It is defined as the ratio of the least amount of UV energy (UVB) required to produce minimal erythema on sunscreen-protected skin to the amount of energy required to produce the same erythema on unprotected skin. As UVB is approximately 1000 times more erythemogenic as compared with UVA, the SPF is largely a measure of protection against UVB.

Substantivity

This term is defined as the ability of a sunscreen to maintain efficacy and withstand adverse conditions such as exposure to water and sweat.[47] The FDA also defines the terms ‘water-resistant’ and ‘very water resistant.’ Water resistance is defined as the ability of a sunscreen to retain its photoprotective properties following two 20-minute intervals (40 minutes total) of moderate activity in water immersion. Very water resistant is defined by doubling aquatic activity time to four 20-minute activity intervals (80 minutes total).[48] Interestingly, the FDA permits products labeled as water resistant or very water resistant to be grouped together under the same term ‘sweat resistant.’[49]

Assessing UVA protection

The in vivo testing methods are immediate pigment darkening (IPD), persistent pigment darkening (PPD), and the protection factor in the UVA (PFA). These methods are expensive, and require unacceptably high UVA exposure to human subjects. IPD describes the immediate gray-brown pigmentation of the skin as caused by the oxidation of preformed melanosomes in the skin. IPD peaks within the first minute after UVA exposure.[13] The transient nature of IPD which requires immediate testing makes it a less than ideal measurement tool of UVA protection.

The PPD method, currently used in Austria and Japan, evaluates sunscreen effectiveness against UVA by measuring melanin photo-oxidation postexposure.[50] PPD is measured between 2 and 24 hours following irradiation and has the added benefit of simultaneously evaluating sunscreen photostability. However, PPD requires subjects be exposed to high-intensity lamps for long periods of time (up to 1 hour).

The PFA has a less inclusive endpoint following UVA irradiation, measuring either erythema or pigmentation (tanning). Like PPD, it is evaluated 24 hours after light exposure.

In vitro models of evaluating UVA protection present a unique set of solutions and challenges. Unlike in vivo testing, laboratory testing may be a more efficient, reproducible, cost-effective testing method. In vitro method of UVA protection is measured by the Diffey critical wavelength determination.[51] In this method, the sunscreen agent is applied to a substrate, and the UV absorbance is measured along a continuum from 290 to 400 nm. It is then calculated as ‘the wavelength below which 90% of sunscreen's UV absorbance occurs.[1349] The UK uses a variation of this in vitro test called the Boots Star rating. The Star system is a ratio of two in vitro tests: the measurement of a product's UVA absorbance to its UVB absorbance.

Ideal Sunscreen

The ideal sunscreen should first and foremost provide superior efficacy with broad-spectrum coverage, photostability, and high substantivity. It should have an appealing feel and uniformly coat the skin surface. Lastly, a sunscreen should be supplied at a reasonable cost to the consumer.

General application recommendations

Application density

The average adult should apply approximately 35 mL for full-body application to cover an area of 1.73 m.[252] In addition to application density, consumers should be educated on overall guidelines for sunscreen use. The sun-protective clothing is a powerful adjunct to topical sunscreens. Clothing should cover skin first, and sunscreen should be used under clothing as well as to exposed skin. Individuals should avoid time spent outdoors between 10 am and 4 pm. Since the time zones and daylight savings time separates solar noon from the ascribed noon time,[53] Ting offers a convenient rule of thumb: ‘If one's shadow is longer than one is tall,’ avoid prolonged outside activity. Eide[54] refers to this as the ‘shadow rule’ and patients should avoid this time, when the solar zenith is less than 45 degrees.

Reapplication

Reapplying sunscreen after initial application is another important step in effective sun safety. Individuals should apply a first coat of sunscreen half an hour before walking out of the door. A second application approximately 20 minutes after initial application is estimated to prevent an additional 65–80% of UV transmission[55] and corrects areas of misapplication.[56] Sunscreen should be reapplied every 2 hours and more frequently during activity-filled days. Up to 85% of a product can be removed by towel drying, so reapplication should occur after swimming, sweating, or any other rigorous activity.

Conclusion

Complete topical photoprotection can only be obtained if a sunscreen formula protects against UVB, UVA, and IRA. The role of additional wavelengths contributing to skin damage is currently not known. In order to achieve a near complete broad spectrum protection as possible, a sunscreen should incorporate molecules of both of primary and secondary photoprotection along with other photoprotective measures.

Questions

MCQ

The effects of UVA include

ageing effects and pigmentation

production of radical oxygen species

decrease in Langerhans cells

increases the expression of p53, a tumor suppressor gene

all of the above

All are UVB blockers except

octinoxate

octisalate

avobenzone

octocrylene

The substance used to stabilize water insoluble sunscreen ingredients is

meridimate

trolamine salicylate

ecamsule

ensulizole

Secondary photoprotection includes all except

Antioxidants

Osmolytes

DNA repair enzymes

Inorganic sunscreens

The clothing material with best UV absorbing capacity is

Cotton

Wool

Polyester

Silk

The adverse effects of nanoparticles include

interface for catalytic reactions

complexes with proteins which can escape immunological surveillance

induction of autoimmune diseases

all of the above

The UV filter which disturbs thyroid hormone homeostasis in rats is

octylmethoxycinnamate

benzophenones

PABA

homosalate

The in vivo methods for measuring UVA protection are all except

immediate pigmentdarkening (IPD)

persistent pigment darkening (PPD)

protection factor in the UVA (PFA)

sun protection factor (SPF)

The average adult should apply approximately ---mLfor full-body application to cover an area of 1.73 m2

25 ml

30 ml

35ml

40ml

Complete topical photoprotection can only be obtained if a sunscreen formula protects against

UVB

UVA

IRA

all of the above

Answers

(e) 2. (c) 3. (b) 4. (d) 5. (c)

6. (d) 7. (b) 8. (d) 9. (c) 10. (d)