INTRODUCTION:

The extraterrestrial sun light composed of X-rays, ultraviolet, visible, infrared radiations, micro and radio waves. The solar spectrum received at the earth’s surface consists of wavelengths of electromagnetic energy between 290 to 3000 nm (1). Ultraviolet (UV) radiations are the electromagnetic radiation with wavelengths between 100 to 400 nm. The UV radiations are further divided in to three bands: UVA (320 to 400 nm), UV B (290-320 nm) and UV C (200-290 nm). The solar UV radiation reaching the earth comprises approximately 95-98% UV A and 2-5% UV B, all the UV C having been absorbed by the ozone at stratosphere (2). UV B radiation is fully absorbed by the stratum corneum and top layers of the epidermis, whereas up to 50% of the incident UV A radiation penetrates Caucasian skin deep in to the dermis (3). Figure 1 shows the extent of penetration of different wavelengths of light in to human skin.

Figure 1: Penetration of different wavelengths of light in to human skin

Nowadays there is an increased concern over the depletion of stratospheric ozone layer by the chlorofluorocarbons, halons and nitric oxides. This may result in irradiance of both UV B and UV C at the earth’s surface that may eventually contribute to higher incidence of skin cancer and other harmful effects to humans.

Exposure to UV radiation has pronounced acute and chronic effects on the skin. The UV radiation induced skin effects manifest as acute responses such as inflammation (sunburn or erythema), pigmentation, hyperplasia, immunosuppression, vitamin D synthesis, and chronic effects such as photocarinogenesis and photoaging. These acute and chronic effects are dependent of the spectrum, intensity and cumulative dose of UV radiation. The complete action spectrum for the majority of UVR-induced effects has not yet been completely defined inhuman skin. In addition, these responses have different thresholds such that the prevention of UVR-induced changes for an endpoint does not guarantee a similar level of protection for any other.

Effects of ultraviolet radiation

Inflammation

Erythemal effectiveness declines rapidly with increasing wavelength, such that approximately 1000times more UVA energy than UVB is required to produce the same erythema response (4). However, due to its preponderance in terrestrial sunlight, UVA none the less contributes significantly to sunburn erythema.

Pigmentation

Ultraviolet A radiation causes immediate transient tanning which is believed to be due to the photo-oxidation of a precursor of melanin. The action spectrum is broad, extending from 320-400 nm, with a peak at around 340 nm. The physiologic significance of this immediate tanning response in humans is not known, as unlike neomelanogenisis, it does not confer photo protective properties (5). Delayed tanning, which is more persistent, is a result of increased formation of epidermal melanin. This is induced by UVB and the shorter UVA wavelengths.

Photoageing

Ultraviolet A radiation, due to the longer wavelengths, can penetrate into and cause damage in the dermis. All UVA bands have been shown to be equally effective in inducing inflammatory changes in the dermis which can lead to connective tissue damage, whereas UVA II is more effective at inducing epidermalchanges (6). Although acute exposure to UVA may not lead to any detectable changes, repeated exposure to UVA, even at suberythemogenic doses, has been shown to have a cumulative effect in human skin causing significant photo damage and immunosuppression (7).

Immunosuppression and carcinogenesis

In the past, it was thought that the cancer risk posed by UVA is negligible, as unlike UVB, it does not cause sunburn. Although we cannot subject humans for prospective studies to document the carcinogenicity of UVA using tumour occurrence as the study endpoint, there is now increasing evidence to suggest the pathogenic role of UVA in cutaneous malignancies. It has been shown that UVA can have an immunosuppressive effect on the human skin (7). UV radiation induced immunosuppression is important as it occurs not only with environmental antigens but also with tumour antigens. It can be directly demonstrated in animals that UVA, including those with wavelengths >340 nm, induce skin tumours (8). In human skin, UVA has been demonstrated to cause DNA breaks and accumulation of p53 protein in melanocytes (9). The epidemiological evidence for the photo-carcinogenicity of UVA is strong. Among individuals with long-term exposure to UVA tanning beds or psoralen plus UVA therapy (PUVA), increased incidence is observed for non-melanoma skin cancer (10, 11). However, the association is less consistent for melanoma (11-13).

Protection by sunscreens

It has been shown that photodamage due to UVA can be reduced or abolished by broad-spectrum sunscreens or the UVA filters but not by sunscreens with attenuation spectrum mainly in the UVB range (7, 14).

Concerning protection against cutaneous malignancies, these endpoints are difficult to evaluate in humans for ethical reasons. However, it has been reported in humans that the use of a broad-spectrum sunscreen can effectively prevent and even reduce solar keratosis, and so by implication, possibly reduces the risk of skin cancer in the long term (15). In vivo studies support that broad-spectrum sunscreens, compared with UVB filters, provide better protection against UV-induced cutaneous malignancies. Broad-spectrum sunscreens are more effective in the reduction of immunosuppression and skin tumours in mice (16, 17), and DNA breaks in human melanocytes (9).

SUNSCREENS

Sun avoidance is the single most effective method of skin cancer and photoaging prevention. Additional sun protection methods include sun-protective clothing and sunscreens. The primary use of sunscreens is to protect the skin from the short and long term effects of the UV radiation. Nowadays sunscreens have become an indispensable part of every patient’s post-procedure skin care routine (18). The common indications for the use of sunscreens in dermatology are in the prevention and management (19) of

1. Sun burn

2. Freckling, discoloration

3. Photoaging

4. Phototoxic/photoallergic reactions

5. Skin cancer

6. Photosensitivity diseases

· Polymorphous light eruption (290-365 nm)

· Solar urticaria (290-515 nm)

· Chronic actinic dermatitis (290 nm – visible)

· Persistent light reaction (290-400 nm)

· Lupus erythematosus (290-330 nm)

· Xeroderma pigmentosum (290-340 nm)

· Albinism

7. Photoaggrevated dermatoses

8. Post-inflammatory hyperpigmentation

In order to ensure optimal patient compliance, an ideal sunscreen would be:

· A combination of physical and chemical agents

· Broad spectrum of activity

· Cosmetically elegant

· Substantive

· Non-irritant

· Hypoallergenic

· Non-comedogenic

· Economical

The sunscreens are broadly classified as ‘organic’ and ‘inorganic’. Apart from these two main classes of sunscreens, systemic photoprotection agents are also available. There are three commonly used nomenclatures for sunscreen agents in the world. These are the International Nomenclature of Cosmetic Ingredients (INCI) Name, United States Adopted Name (USAN) and trade name. Taking avobenzone (USAN) as an example, the INCI name for avobenzone is butylmethoxydibenzoylmethane, while Parsol 1789 is one of its many trade names (20-22).

Organic sunscreens

Organic sunscreens or UV filters are active ingredients that absorb UV radiations within a particular range of wavelengths, depending on their chemical structure. They are generally aromatic compounds conjugated with carbonyl group. In most of the cases, the electron releasing group (an amine or a methoxyl group) is substituted in the ortho- or para- position of the aromatic ring as shown in figure 2.

Sunscreens of this configuration absorb the harmful high energy UV radiation (of wavelength from 250 to 340 nm) and convert the remaining energy in to mild longer wave (low energy) radiation (of wavelength above 380 nm). Quantum mechanical calculations have shown that the energy of the radiation quanta present in the UVB and UVA region lies in the same order of magnitude as that of the resonance energy of electron delocalization in aromatic compounds (Figure 3).

Thus the energy absorbed from the UV radiation corresponds to the energy required to cause a “photochemical excitation” in the sunscreen molecule. In other words, the sunscreen chemical is excited to a high energy state (π*) from its ground state (n) by absorbing this UV radiation. As the excited molecule return to the ground state, energy is emitted that is lower in magnitude than the energy initially absorbed to cause the excitation. Thus, the energy is emitted in the form of longer wavelengths because the energy is lower than the shorter wavelengths originally absorbed.

The longer wavelength radiation is emitted in one of the several ways (Fig. 4). If the loss in energy is quite large, that is, the wavelength of the emitted radiation is sufficient length that it lies in the infrared region, it may be perceived as a mild heat radiation on the skin. This miniscule heat effect is undetected because the skin receives a much larger heat effect by being directly exposed to the sun’s heat.

Figure 2: General chemical structure of most sunscreen chemicals approved for use in the United States, where Y = OH, OCH3, NH2, N(CH3)2; and X = no substituent or –CH=CH-, and R = C6H4Y, OH, OR’ (R’ = methyl, amyl, octyl, menthyl or homomenthyl)

Figure 3: Resonance delocalization of electrons in a p-amino benzoate molecule

Table 1: FDA sunscreen final monograph ingredients

Active ingredients	Maximum concentration	Peak absorption λ (nm)	UV action spectrum
Organic sunscreens
UVA filters
Benzophenones
Oxybenzone (Benzophenone-3)	6	288, 325	UVB, UVA II
Sulisobenzone (Benzophenone-4)	10	366	UVB, UVA II
Dioxybenzone (Benzophenone-8)	3	352	UVB, UVA II
Dibenzoylmethanes
Avobenzone (Parsol 1789)	3	360	UVA I
Anthralates
Meradimate (menthyl anthranilate)	5	340	UVA II
Camphors
Ecamsule^a (Mexoryl SX)	10	345	UVB, UVA
UVB filters
Aminobenzoates (PABA derivatives)
PABA (p-aminobenzoic acid)	15	283	UVB
Padimate-O (Octyl dimethyl PABA)	8	311	UVB
Cinnamates
Cinoxate (2-ethoxyethyl p-methoxycinnamate)	3	289	UVB
Octinoxate (Octyl methoxycinnamate)	7.5	311	UVB
Salicylates
Octisalate (Octyl salicylate)	5	307	UVB
Homosalate (Homomenthyl salicylate)	15	306	UVB
Trolamine Salicylate (triethanolamine salicylate)	12		UVB
Others
Octocrylene	10	303	UVB, UVA II
Ensulizole (Phenylbenzimidazole sulfonic acid)	4	310	UVB
Inorganic filters
Titanium dioxide	25		UVB, UVA^b
Zinc oxide	25		UVB, UVA^b

^aOnly as a component of certain approved sunscreen formulations approved under the new drug application

^bAbsorption varies depending on the particle size

Table 2: Skin types determined by historical response to sun^a

Type	Definitions
I	Always burn easily; never tans (sensitive)
II	Always burns easily; tans minimally (sensitive)
III	Burns moderately; tans gradually (light brown)
IV	Burns minimally; always tans well (moderate brown)
V	Rarely burns; tans profusely (dark brown; insensitive)
VI	Never burns; deeply pigmented (insensitive)

^aBased on 30 to 40 min of sun exposure in early summer without previous sun exposure that season

Table 3: Chronological evolution of the main methods for determining the SPF

Year	Institution or Regulatory Authority	Territory
1978	Food and Drug Administration (FDA)	United States
1983	Standards Association of Australia (SAA)	Australia
1985	Deutches Institut fur Normung (DIN)	Germany
1991	Commission Internationale De L'Eclairage (CIE)	International
1992	Japanese Cosmetic Industry Association (JCIA)	Japan
1993	FDA – Review	United States
1994	European Cosmetic and Toiletries Association (COLIPA)	Europe
1998	Australia Standards / New Zealand Standards (AS / NZS) – Review	Australia and New Zealand
1999	FDA – Review	United States
2003	International Sun Protection Factor Method (COLIPA / JCIA / CTFA - SA)	Europe, Japan and South Africa
2006	International Sun Protection Factor Method - Review (COLIPA / JCIA / CTFA - AS / CTFA - USA)	Europe, Japan, South Africa and USA
2007/2008	FDA – Review	United States

Table 4: Comparison of methods for determination of SPF: FDA 1999 and International SPF test method

Methodology	FDA 1999	International SPF method 2006 (CTFA, COLIPA, JCIA)
Light source	Solar Simulator with Xenon Arc Lamp	Solar Simulator with Xenon Arc Lamp
Volunteers	Maximum of 25 included ≥ 20 for valid data	Maximum of 20 included ≥ 10 for valid data
Phototypes of volunteers (Fitzpatrick)	I-III	I-III
Region of Application	Lower back	Lower back
Standard Product	HMS 8%	P1, P2, P3 or P7 (SPF <20) P2 or P3 ( SPF > 20)
Amount of application	2mg/cm² or 2µL/cm² (grav. esp.= 1)	2mg/cm² ± 2.5%
Waiting Period	≥ 15 min.	15 to 30 min.
Progression of Doses	SPF <8: 0.64X, 0.80X, 0.90X, 1.00X, 1.10X, 1.25x, 1.56X ≤ 15 ≤ 8 SPF: 0.69X, 0.83x, 0.91X, 1.00X, 1.09X, 1.20X, 1.44X SPF> 15: 0.76X, 0.87X, 0.93X, 1.00X, 1.07X, 1.15x, 1.32X	SPF ≤ 25: 25% SPF> 25: 12%
Reading of MED	22-24 hr	16-24 hr
Determination of final SPF	Mean SPF value of the group - CI95%	Mean SPF value of the Group
Statistical criteria for acceptance		CI 95% within the interval ± 17% of mean SPF

Table 5: Normalised product function used in the calculation of SPF (in-vitro)

Wavelength (λ nm)	EE x I (normalized)
290	0.0150
295	0.0817
300	0.2874
305	0.3278
310	0.1864
315	0.0839
320	1.0000

Where EE – Erythemal effect spectrum; I – Solar intensity spectrum

Natural sunscreens

There is increasing evidence that various natural compounds offer UV radiation protection. However, natural compounds do not scatter or absorb UV radiation but rather protect the skin cells from being damaged by UV radiation, mostly through their antioxidant effects. The important group of compounds acts as the sunscreens includes phenolic acids, flavonoids and high molecular weight polyphenols (30). Naturally occurring phenolic acids include hydroxycinnamic acid and hydroxyl benzoic acid. High molecular weight polyphenols include condensed polymers of catechins or epicatechins and hydrolysable polymers of gallic and ellagic acids. Many flavonoids such as quercetin, luteolin and catechins are found to be better antioxidants as well as UV blocker (31-32). Evidence of effective photoprotection has been accumulating with green and black tea (33-36). Various other agents used as natural sunscreens are aloevera, sandal, curcumin, carrot, tomatoes, grapes, gingko biloba etc., (37-39).

Systemic photoprotection

Systemic agents have been investigated for photoprotection since they provide protection for the entire body and are likely to eliminate the problem of substantivity which is important for topical products (40).

Oral agents that have been tried include (Para amino benzoic acid) PABA, indomethacin, retinol, steroids, psoralen, antimalarials and antioxidants like Vitamin A, Vitamin C, Vitamin E and beta-carotene. Anti-oxidants are less potent than sunscreens in preventing sunburn (41).

Sun protection factor (SPF)

The level of sun protection has traditionally been estimated using the sun protection factor or SPF test, which utilizes the erythemal response of the skin to UV radiation (42). SPF is the ratio calculated from the energies required to induce a minimum erythemal response with and without sun care product applied on the skin of human volunteers, using ultraviolet radiation usually from an artificial source.

SPF = MED (protected skin) / MED (unprotected skin)

SPF is primarily a measure of UVB protection, as UVB is 1000 times more erythemogenic than UVA. Moreover, high SPF products allow individuals to spend greater amounts of time in the sun without developing erythema (burning). These products do not necessarily offer adequate UVA protection. Protection against UVA is becoming a major concern because UVA damage is now implicated in photocarcinogenesis, photoaging and immunosuppression.

The test works out how much UV radiation (mostly UVB) it takes to cause a barely detectable sunburn on a given person with and without sunscreen applied. For example, if it takes 10 minutes to burn without a sunscreen and100 minutes to burn with a sunscreen, then the SPF of that sunscreen is 10 (100/10). A sunscreen with a SPF of 15 provides >93% protection against UVB. Protection against UVB is increased to 97% with SPF of 30+. The difference between a SPF 15 and a SPF 30 sunscreen may not have a noticeable difference in actual use as the effectiveness of a sunscreen has more to do with how much of it is applied, how often it is applied, whether the person is sweating heavily or being exposed to water. Hence a sunscreen with SPF 15+ should provide adequate protection as long as it is being used correctly.

In-vivo determination of SPF

The first report on the evaluation of the protective efficacy of sunscreens was done by Friedrich Ellinger in 1934 (43) in which the author determined the minimal erythemal dose (MED) for protected and unprotected skin, using both forearms and a mercury lamp. He proposed a coefficient of protection that decreased in value to the extent that protection increased

In 1956, Rudolf Schulze (44) evaluated commercially available sunscreens by calculating a protection factor, later called “Schulze Factor”. The author divided the exposure time required for the induction of erythema on sunscreen-protected skin by the time required for the production of erythema on unprotected skin, using incremental doses of radiation emitted by lamps with a radiation spectrum closer to sunlight. The Schulze method has been used for decades in European countries, as a reference in the evaluation of sunscreens.

It was only in 1974 that the term Sun Protection Factor (SPF) was introduced by Greiter (45), being only a new name for the already known “Schulze method.” The Sun Protection Factor, proposed by Greiter, quickly became popular and used worldwide. However, due to the lack of standardization of the method, the numerical values found and used in sunscreens varied considerably, not rendering it reliable (46).

In 1978, the North-American regulatory agency (FDA) proposed the first normatization to determine the sun protection factor (SPF) (47). To determine SPF, a group of 10 to 20 volunteers with skin phototypes I-III (Fitzpatrick classification as given in Table 2.) (48), are selected and subjected to increasing doses of UV radiation emitted by an artificial light source called solar simulator, in areas of unprotected and sunscreen protected skin in the amount of 2 mg/cm². After about 16 to 24 hours of exposure the reading of the MED in both the areas are done and the ratio calculated. The mean value found for the group of volunteers is the SPF of the product.

Followed by the publication of method by the FDA in 1978, new methods were proposed for the determination of SPF by many international regulatory agencies. The German agency Deutches Institut fur Normung (DIN) presented a new version of the method in 1984, called DIN 67501, at that time used throughout Europe (46). Methodological differences between them were large and mainly referred to the emitting source of ultraviolet (Xenon Arc lamp for the FDA Methodology and natural light or Mercury lamp for DIN) and the amount of sunscreen applied (2.0mg/cm² for the FDA methodology and 1.5mg/cm² for DIN) (46). All the following publications maintained the methodological concepts described in the monograph presented by the FDA in 1978, that is, xenon arc lamp as the emitting source and the amount of 2.0mg/cm² as the standard amount of sunscreen to be applied.

After the first publication in 1978 (47), the FDA produced its proposal of a final monograph in 1993 (49) and, finally, the final monograph in 1999 (50). Currently a new methodological revision proposed by the FDA at the end of 2007 is under discussion (51). In addition to the FDA action, other institutions and international regulatory agencies have produced technical monographs describing the procedures necessary for conducting a clinical trial to assess sunscreen efficacy by determining the Sun Protection Factor (46).

The European community, through the European Cosmetic, Toiletry and Fragrance Association (Comité de Liason des Associations et Européenes de lndustrie et de la Parfumerie - COLIPA) developed its first version of a monograph in 1994 (52). In 2003 the method called International Sun Protection Factor Test Method (ISPF) was presented jointly by the European (COLIPA), Japanese (JCIA) and South African (CTFA-SA) associations (53), followed by a subsequent revision in 2006, with the introduction of Cosmetic, Toiletry and Fragrance Association of the United States (CTFA-USA) (54). The North American (FDA) and European (COLIPA or international) methodologies have become a reference for determining the Sun Protection Factor (SPF) in different countries, among them Brazil, which through Resolution RDC 237 issued by the National Health Surveillance Agency (ANVISA) in 2002 (55) determines that any product denominated sunscreen should present studies showing its photoprotective effectiveness (SPF determination test) through one of two international methodologies: FDA 1993 Methodology (49) or COLIPA 1994 (52) or even through one of their updates.

Table 3 shows all the publications about methods for determining the FPS that have been presented by authorities since 1978 (46). Because these are the most currently employed methods in Brazil and other countries in the world, Table 2 shows the main methodological characteristics and the main differences of the methods for determining the FPS published by the FDA 1999 (standard method in North America) and the International Sun Protection Factor Method (ISPF) 2006 (54) (standard method in the EU and Japan).

Despite the methodological differences shown in Table 2, studies on SPF conducted by the two different methods mentioned (FDA method and International method) yield similar results. In practice, we understand that the two methods produce equivalent SPF values.

Developed over thirty years, the Sun Protection Factor (SPF) is the most accepted method for evaluating the photoprotective efficacy of sunscreens, being universally considered as the main information in the labeling of sunscreens. Still, there are controversies regarding the method and its applicability in real conditions of use. Because it uses a biological marker with individual variable response, such as erythema, the SPF is a method that can vary in its results.

It is important to know that the efficacy of sunscreens are influenced by other ingredients in a formulation and that a certain concentration of a sunscreen in a product leads to different sun protection dependent on the type of skin, mode of application, and grade of UV exposure. Therefore, it is not possible to make a product with an exact SPF. It is always an approximate approach. If more than one sunscreen are combined in a product, determination of the SPF becomes even more difficult (56).

In-vitro methods of determination of SPF

The methods in vitro are in general of two types. Methods which involve the measurement of absorption or the transmission of UV radiation through sunscreen product films in quartz plates or biomembranes, and methods in which the absorption characteristics of the sunscreens agents are determined based on spectrophotometric analysis of dilute solutions (57-61).

Mansur et al. (1986), developed a very simple mathematical equation which substitutes the in vitro method proposed by Sayre et al., (1979), utilizing UV spectrophotometry (62) and the following equation:

Where: EE (l) – erythemal effect spectrum; I (l) – solar intensity spectrum; Abs (l)- absorbance of sunscreen product ; CF – correction factor (= 10).

It was determined so that a standard sunscreen formulation containg 8% homosalate presented a SPF value of 4, determined by UV spectrophotometry (59). The values of EE x I are constants. They were determined by Sayre et al. (1979), and are showed in Table 5

Substrate methods have been widely used for the determination of SPF in-vitro. The ideal substrate for in vitro SPF needs to be fairly transparent to the ultraviolet and simulate the porosity and texture of human skin, the in vivo substrate. Suitable in vitro substrates range from human epidermis and mice epidermis to sausage casings and natural lamb condoms. The three common substrates used are Transpore Tape, Vitro-Skin, and Polyvinyl Chloride Film

Transpore tape

It is a surgical tape manufactured by the 3M Company. The tape is readily available and inexpensive. The adhesive side makes it easy to apply to a quartz microscope slide for a rigid working surface. Although the tape is discarded for each prepared sample, the quartz slides can be washed and used again. The use of this substrate was first evaluated by Diffey and Robson (63). It was selected for its uneven topography that distributes the sunscreen in a way similar to human skin. The method gives the reproducible results. The main advantages of the Transpore tape are its low cost, ready availability, and ease of use. There are a few disadvantages that need consideration when using Transpore tape: (a) the tape will not absorb formulations that use alcohol or oil as a vehicle; (b) pore size can vary at the beginning and end of each roll therefore, it is recommended to discard the first two feet at the start and end of each roll; (c) the pore size can vary batch-to-batch – it is advisable to screen at least 4 rolls to determine the suitability of a larger batch (screening involves measuring a standard sunscreen formula of known SPF); (d) complex formulations using multiple organic active ingredients have shown poor correlation (64). This may be due to a swelling of the tape’s substrate or a solvation of some of the tape’s adhesive.

Vitro-Skin

Vitro-Skin, a registered trademark of IMS Inc., is a synthetic skin substitute that has been widely used for in vitro analysis of sunscreens (65). Once hydrated, Vitro-Skin has a texture very similar to human epidermis. In addition, the hydrated material seems to help sunscreen emulsions break down in much the same way as human skin. Published data by the producer of Vitro-Skin indicates that the substrate gives excellent correlation with in vivo SPF measurements. The primary advantages of Vitro-Skin are its topographical similarity to human skin and the ability to break down emulsions. The apparent disadvantages are: (a) a relatively high cost per sample- approximately $1.50 per test compared to pennies for other methods; (b) an overall low UV transmittance, especially at low wavelengths; (c) the need to hydrate the substrate starting the day before testing; (d) a relative short lifetime of the hydrated Vitro-Skin

Polyvinyl Chloride Film

Polyvinyl chloride or polyvinylidene chloride film, available under the commercial trade name Saran Wrap®, is a highly transmissive material in the UV-Visible portion of the spectrum (65). While the film does not have the texture of human skin, it is very easy to form uniform dispersions of sunscreen products on the material. Commercially available polyvinyl/vinylidene chloride films are also extremely uniform in their material properties from roll to roll, and throughout each individual roll.

The primary advantages of polyvinyl chloride films are its availability, very high UV transmittance, ease of sample preparation, and low per sample cost. The disadvantages are: (a) the texture does not approximate that of human skin; (b) literature references to using polyvinyl chloride film as a substrate for SPF measurement are only anecdotal; (c) certain materials that claim sun protection such as lip balms or liquid cosmetics may not disperse well on the films.

Future trends on sunscreen research

Novel substances with photoprotective potential are being investigated. Potent and long lasting derivatives of alpha-MSH have been synthesized and shown to induce synthesis of melanin (tanning) in humans when administrated subcutaneously (66-69).

Of interest, melanin synthesis appears to increase more in individuals with light skin that usually do not tan but burn when exposed to sunlight. The alphamsh induced melanin may have a photoprotective effect. Specifically, it reduces the formation of epidermal sunburn cells and of thymine dimmers after skin exposure to ultraviolet light (67). T4 endonuclease V (T4N5) is a DNA repair enzyme in bacteria. It has also been shown to accelerate the repair of DNA in human cells when it is delivered intracellularly. The topical use of T4NV has been investigated in patients with xeroderma pigmentosum, a defect in nucleotide excision repair of DNA, and found to have a protective effect on the appearance of basal cell carcinoma and actinic keratosis (70).

Application of T4N5 immediately after UV exposure partially protects against sunburn cell formation However, it has little or no effect on UV-induced skin oedema (71). Thymidine dinucleotide (pTT) is a small DNA fragment that induces a photo-protective response in mammalian cells and intact skin. Specifically, topical pTT pretreatment enhances the rate of DNA photoproduct removal, decreases UV-induced mutations and reduces photocarcinogenesis in UV-irradiated hairless mice (72).

The protective effects of pTT are attributed to its partial sequence homology with the mammalian telomere repeat sequence 5′-TTAGGG-3′. In mammalian cells, telomeres are tandem repeats of a short DNA sequence TTAGGG that cap chromosome ends and form a large loop structure (73). Disruption of this loop structure is hypothesized to lead to exposure of the 3′-overhang sequence (repeats of TTAGGG), digestion of the overhang, and signaling that induces DNA damage responses. It has been suggested that providing cells with DNA oligonucleotides partially or totally homologous to the telomere sequence (like pTT), initiates signalling for DNA damage-like responses without antecedent DNA damage (73). The photoprotective potential of pTT remains to be evaluated in humans.

CONCLUSION:

Increasing evidence points to the deleterious effects of chronic UVA exposure. It is therefore advisable to choose sunscreen products that protect against both UVB and UVA. With the development of new chemical filters, UVA protection can be now achieved without solely relying on physical filters, which are often found to be cosmetically unacceptable. It is not enough to look at the SPF value alone when evaluating sunscreens, as SPF cannot reflect the level of protection against UVA. So far, no side effects have been confirmed to be associated with long-term sunscreen usage. Regular use of high protection factor broad-spectrum sunscreen, and proper application, can probably reduce the chronic effects of sunlight exposure, namely photoaging and photocarcinogenesis

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Received on 28.02.2015 Accepted on 05.03.2015

Research J. Topical and Cosmetic Sci. 6(2): July-Dec. 2015 page 55-65

DOI: 10.5958/2321-5844.2015.00009.6