Its known that compared with UVB, UVA radiation is a tenfold more efficient oxidative stress generator causing lipid peroxidation linked to plasma membrane damage (Damiani et al. 2006). In vitro studies indicate UVA generates a peroxidative process in cultured human skin fibroblasts and in keratinocytes, a radical process that alters the plasma membrane. Exposure of keratinocytes to 15 min UVA radiation has been shown to result in substantial cell mortality and a protein content decrease (Armeni et al. 2004). Such physiological changes have adverse effects on the overall skin structure and serves to initiate various skin maladies.
The cancer induction mechanism by UVA and UVB radiation is well documented. Absorption of UVA and UVB radiation causes pyrimidine bases in the DNA molecule to form dimers (González et al. 2008); resulting in transcription errors during DNA replication. The malignant type of cancer manifests tumours as a consequence of abnormal proliferating skin cells. The uncontrollable growth of these cells leads to melanoma tumours forming. Melanoma is a cancerous skin tumour, produced by cells in the skin that give it pigment (melanin), cells called melanocytes. Melanoma begins as a dark skin lesion and may spread rapidly to other skin areas and within the body (Besaratinia and Pfeifer 2008). Usually, melanoma skin cancer is caused by longer, deeper penetrating UVA rays.
They penetrate the dermal layer and cause elastosis (loss of structural support and elasticity of the skin) (Atitaya et al. 2011). Melanomas are therefore linked to UVA radiation but other experiments on opossums suggest a larger role for UVB (van der Leun and de Gruijl 2002). Consequently both UVA and UVB radiation have therefore been linked to skin cancer, whether malignant or benign (Abarca and Casiccia 2002). The most lethal of the skin cancers, cutaneous malignant melanoma, is more commonly associated with sporadic burning exposure to solar radiation. There are several indications that UVA might have an important role in the pathogenesis of melanoma (Lautenschlager et al. 2007). But sunburns are taken as a measure of overexposure to solar radiation and they have been identified as a risk factor for the development of melanoma. It is on the basis of sunburns;
primarily due to UVB that implicates UVB as a potential contributing factor to the pathogenesis of melanoma. To this end there is a great deal of controversy regarding the relationship between UVA exposure and the development of melanoma (Wang et al. 2001). Nonetheless, cutaneous malignant melanoma is one of the fastest increasing cancers and UV radiation is strongly linked in its etiology (De Fabo et al. 2004). Cutaneous malignant melanoma is more prevalent among light-skinned people (Abarca and Casiccia 2002).
The other solar radiation associated skin conditions are basal and squamous cell carcinomas, which are common forms of skin cancer in humans. These cancers (BCC and SCC) are relatively mild and rarely fatal, although the treatment of squamous cell carcinoma sometimes requires extensive reconstructive surgery. Other UV radiation induced skin disorders are: photoaging; actinic keratosis;
lupus vulgaris (tuberculosis of the skin), and psoriasis or vitiligo (a discontinuous depigmentation of the skin). Hence, sun protection is an inevitable choice, and suitable vehicles are required to deliver the sunscreen ingredient onto the skin or in clothing fabric.
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aesthetic value.
Emulsions are more popular, being termed creams or lotions depending on their degree of viscosity;
though no clear-cut distinction between a cream and a lotion exists. However, both are easier to spread on the skin and dispense from bottles. Due to ease of surface dispersion it is possible to achieve a uniform thickness, non-transparent sunscreen film and hence minimum ingredient interaction with sunscreen-active components. It is because of these factors that make emulsion formulations to afford higher SPF values. However, emulsions are difficult to stabilize especially at elevated temperatures, creating a favourable environment for microbial contamination and risking product breakdown. Undeniably emulsions are the best medium that gives skin suppleness and a smooth silky feel.
Oils have the advantage of ease of formulation and excellent product stability. Given that most sunscreen ingredients are lipophilic in nature dissolution in oils makes their manufacture simpler compared to emulsions. Application of oils on the skin yields a thinner, uniform layer, and a transparent film screen greatly reducing SPF. It has been demonstrated that oils, like mineral oils, have a hypochromic shift effect on UV filters as a result of interactions with nonpolar esters that constitute the most popular sunscreens (Kwok et al. 2008). Chemical reactions between esters in sunscreen oils may produce products likely to react with the plastic casing housing a product. This offers an additional cost effect rolled over to consumers, since suitable packaging is required.
Gels, on the other hand, present as crystal clear films when spread on the skin give an impression of high purity, class and fashion. There are four classes of gels: aqueous, hydro-alcoholic, micro- emulsion and gelled-oleaginous (oily anhydrous). Each of these vehicles have corresponding disadvantages, for example, aqueous gels are prone to wash off when exposed to water or perspiration. Use of a high concentration of surfactants makes the finished product both expensive and time-consuming. Hydro-alcoholic gels give a good cooling effect on the skin. Most lipophilic screens are soluble in ethanol thus additional solubilizers are not required. However, the main limitations of this vehicle are water wash-ability and eye itch due to the high levels of alcohol.
Volatility of alcohol is another challenge demanding special packaging thereby increasing the cost of production. Micro-emulsion gels have particle sizes in the range of < 0.5 µm. They afford an elegant feel to the skin creating a smooth, thick and uniform film when dispersed on the skin. A challenge with this mode of sunscreen presentation is the use of high emulsifier levels known to irritate and increase wash-ability. Oily gels are produced by crystallizing a combination of mineral oils and sunscreens with special silica making them clear. This vehicle is not very popular due to cost of production.
Popular among the feminine gender is the need to cover smaller sections of the body, such as the lips or nose; here sunscreen-sticks comes in handy. Most sticks are composed of oils and oil-soluble sun- active ingredients thickened by incorporation of waxes and petrolatum, thereby enhancing water resistance (Kwok et al. 2008). For outdoor workers the vehicle of choice is ointments; they are hard to remove or wash away but aesthetically not appealing due to their oily and greasy nature. Other vehicles in the market are mousses and aerosols but associated sun protection factors are much less.
All vehicles discussed above have to carry several inorganic and organic compounds employed to absorb or scatter/reflect deleterious UV radiation. The quantity of these compounds in commercial sun protection formulations is generally decided by the SPF. A given sunscreen product must have a minimum SPF of less than the number of active sunscreen ingredients used in combination multiplied by two (Jain and Jain 2010).
Since both UVB and UVA radiation are carcinogens, sunscreen products should achieve broad- spectrum protection, that is, UVA and UVB protection. Problems of photoinstability of such products have been reported (Mturi and Martincigh 2008; Azusa et al. 2009; Kockler et al. 2012) and consequently the photostability of the protective molecules needs to be optimized. Any photo- generated reactive species should be quenched before photochemical damage occurs. Suncare chemicals are classified into two main classes: physical blockers and chemical absorbers.
Physical blockers, in sufficient amount and monodispersed on the skin surface should reflect or scatter all UV, visible and infrared radiation. The most commonly used physical blockers are titanium oxide, zinc oxide and red petrolatum. In most formulations they are used in conjunction with chemical absorbers to achieve high SPF factors. Other forms of metal oxides and dopants are being investigated to enhance sun protection and increase aesthetic value of formulations (Herling et al.
2013). Chemical absorbers, on the other hand, are classified depending on the type of radiation they protect that is either UVA or UVB. Sunscreen ingredients that absorb in the UVA range (315-400 nm) are classified as UVA absorbers. Examples are derivatives of benzophenone, anthranilate; and dibenzoylmethane. Those absorbing between 290-315 nm, for example salicylates, cinnamates, camphor derivatives and p-amino benzoic acid derivatives, are classified as UVB absorbers (Atitaya et al. 2011).
The chemical environment in which a sunscreen absorber is packaged greatly determines its UV absorptivity. Acidic chemical absorbers in alkaline conditions favour formation of anions that tend to increase electron delocalization. This decreases the energy required for electronic transitions in the UV region and thus a shift to longer wavelength is observed (bathochromic shift). Similarly, tert- butylmethoxy dibenzoylmethane (BMDBM) a common UVA absorber has been shown to stabilize in polar protic environments that favour the chelated enol form (Mturi and Martincigh 2008) that enhances its absorptivity in the UVA region. Several other published works show a relationship between the chemical structure and efficacy of UV filters. For example, 4-methylbenzylidene camphor (4-MBC), a UV filter with a high molar absorption coefficient of above 20000 dm3 mol-1 cm-
1 absorbs in the UVB range of 290-300 nm. This molecule owes its photostability to the reversible photo-isomerization (Fig. 3.2). A chemical environment that would favour carbonyl-hydrogen abstraction is therefore likely to interfere with the reversibility of the isomerisation and hence induce a loss in photostability.
O
O h
Figure 3.4 Photo-isomerization of 4-methylbenzylidene camphor (Shaath 2010).
UVA (315-400 nm) penetrates to deeper layers of the skin damaging DNA and tissue via production of reactive oxygen species (ROS) (Setlow et al. 1993). In addressing the effects of UVA damage it has been necessary to search for broad-spectrum UV radiation filters. A common UVA absorber used BMDBM, is known to be inherently photolabile and requires special selection of formula ingredients to provide photostable protection (Wang et al. 2008). Innovative stabilizing strategies for BMDBM have been investigated. Chaudhuri et al. (2006) showed diethylhexyl syringylidene malonate as a potent stabilizer of BMDBM and effective antioxidant. Recently Santo and Mezzena (2010)
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demonstrated that addition of quercetin to the sunscreen formulation significantly reduced the photodegradation of the combination of BMDBM and EHMC, a mixture known to be photolabile.
The photodegradation of suncare molecule produces by-products that are potentially dangerous, since they may induce sensitization and skin irritation. Several techniques are available to reduce photodegradation. These include:
Use of different UV filters in the same product, to enhance the synergistic effect,
Incorporation of specific stable UV filters that absorb at a specific wavelength, and
Protecting the active ingredient by complexing or encapsulation.
This review aims at exploring current formulations and pointing out novel approaches for suncare product development and presentation.