Changes in ultraviolet absorbance and hence in protective efficacy against lipid peroxidation of organic sunscreens after UVA irradiation

Owing to the spectral distribution of solar UV, the UVA component of sunlight is now believed to be the main cause of photoaging and photocarcinogenesis and is much more effective than UVB in inducing peroxidative damage. Consequently, most skin care cosmetic products now include UVA filters in their formulations along with UVB filters. These modern sunscreens should provide and maintain their initial absorbance, hence protection, throughout the entire period of exposure to sunlight. However, not all UVA and UVB filters are sufficiently photostable. In this study, we examine the correlation between the photochemical degradation of sunscreen agents under UVA irradiation, with particular reference to the UVA-absorber 4-tert-butyl-4'-methoxydibenzoylmethane, alone and in combination with other organic UV filters (2-ethylhexyl 4 methoxycinnamate and 2-ethylhexyl 2-cyano-3,3-diphenylacrylate) and their ability to prevent UVA-induced lipid peroxidation. Since antioxidants are also added to formulations to deactivate free radicals generated during UVA exposure, vitamin E and the synthetic antioxidant, bis(2,2,6,6-tetramethyl-1-oxyl-piperidine-4-yl)sebacate, a nitroxide derivative, were also included in this study. By using simple in vitro tests, the results show that a decrease in spectral absorbance of the UV filters correlates in most cases with increased UVA-induced lipid peroxidation; this depends on the specific UV absorber analysed and also on whether they are alone or in combination. Furthermore, the combined presence or absence of antioxidants has a profound effect on this oxidative event. In particular, the nitroxide appears to be a more efficient photo-antioxidant than vitamin E. Similar experiments were also performed under natural sunlight and the results obtained did not differ substantially from those performed under UVA. The results presented and discussed in this work may help in understanding the effects of UVA/UVB absorbers and antioxidants upon the level of UV-induced ROS generated under UVA exposure and in natural sunlight which could be relevant for improving the photoprotection and efficacy of skin care cosmetic formulations.     

Radical protection by sunscreens in the infrared spectral range

One essential reason for skin ageing is the formation of free radicals by excessive or unprotected sun exposure. Recently, free radical generation in skin has been shown to appear not only after irradiation in the UV wavelength range but also in the infrared (IR) spectral range. Sunscreens are known to protect against radicals generated by UV radiation; however, no data exist for those generated by IR radiation. This paper has investigated four different, commercially available sunscreens and one COLIPA standard with regard to radical formation in the skin after IR irradiation, using electron paramagnetic resonance spectroscopy. The use of sunscreens has led to reduced amounts of radicals compared to untreated skin. Furthermore, absorption and scattering properties and the radical protection factor of the formulations were determined to investigate their influence on the radical protection of the skin. None of these formulations contained an optical absorber in the IR range. The protection efficiency of the sunscreens was shown as being induced by the high scattering properties of the sunscreens, as well as the antioxidants contained in the formulations.     

A Review of Sunscreen Safety and Efficacy

The use of sunscreen products has been advocated by many health care practitioners as a means to reduce skin damage produced by ultraviolet radiation (UVR) from sunlight. There is a need to better understand the efficacy and safety of sunscreen products given this ongoing campaign encouraging their use. The approach used to establish sunscreen efficacy, sun protection factor (SPF), is a useful assessment of primarily UVB (290–320 nm) filters. The SPF test, however, does not adequately assess the complete photoprotective profile of sunscreens specifically against long wavelength UVAI (340–400 nm). Moreover, to date, there is no singular, agreed upon method for evaluating UVA efficacy despite the immediate and seemingly urgent consumer need to develop sunscreen products that provide broad-spectrum UVB and UVA photoprotection. With regard to the safety of UVB and UVA filters, the current list of commonly used organic and inorganic sunscreens has favorable toxico-logical profiles based on acute, subchronic and chronic animal or human studies. Further, in most studies, sunscreens have been shown to prevent the damaging effects of UVR exposure. Thus, based on this review of currently available data, it is concluded that sunscreen ingredients or products do not pose a human health concern. Further, the regular use of appropriate broad-spectrum sunscreen products could have a significant and favorable impact on public health as part of an overall strategy to reduce UVR exposure.     

Inclusion complexes of <Emphasis Type="Italic">p</Emphasis>-hydroxybenzoic acid esters and γ-cyclodextrin

The alkyl esters of p-hydroxybenzoic acid (parabens) are commonly used as preservatives in cosmetics, food products and pharmaceutical formulations because of their wide range antimicrobial activity. However, the usage of parabens in aqueous media has been hampered, especially parabens with long alkyl chains, due to their low aqueous solubility. One approach to increase their solubility is cyclodextrins (CDs) complexation to form water-soluble inclusion complexes. γCD has the widest hydrophobic central cavity and the highest water solubility among natural CDs. Hence, inclusion complexes between γCD and parabens of various alkyl chain lengths were investigated. Results from phase-solubility studies show that methyl- and ethylparaben form various complexes of paraben/γCD (i.e. 1:1, 2:1, etc.) while the 1:1 complex was dominant in propyl- and butylparaben/γCD complex solution. Moreover, the effect of the paraben complexation on the critical aggregation concentration (cac) of γCD in aqueous solutions was determined. It was found that the longer the paraben alkyl chain was the more influence it had on the γCD cac. In pharmaceutical formulations the mixture of parabens (i.e. binary, ternary and quaternary) has been used to maximize antimicrobial effect. It is important to determine how mixtures of parabens affect the solubility of γCD and its cac values upon formation of inclusion complexes. Competition of the different parabens for a space in the γCD central cavity was evaluated by comparing the γCD cac values obtained in presence of the individual parabens and their mixtures.     

A mini-review on limitations associated with UV filters

Ultraviolet light from the sun can produce long-term skin damage and cancer. The use of sunscreen products containing one or more UV filters is encouraged by health professionals for preventing the damaging effects resulting from sun exposure. However, recently there have been increasing concerns about the use of sunscreens and their safety for both humans and the environment. The sunscreen manufacturers should take the initiative in testing of the products for possible short-term skin toxicity and long-term health effects that might occur due to the absorption of UV filters through the skin. Published studies have shed light on this topic by investigating the harmful effects of UV filters such as oxybenzone on the hormone system of aquatic animals and humans. Currently, in vitro and in vivo animal models are being used to determine the mechanistic and cellular effects these products produce. With growing awareness of adverse effects posed by UV filters on the environment and exposed organisms, several jurisdictions are prohibiting their use in sunscreens. To our knowledge, very few reviews summarized the potential toxicities associated with UV filters. Therefore, the current reported findings are rather controversial due to the lack of nonclinical safety assessment data to determine the clinical significance of such exposure.     

Recent developments in chemistry of sunscreens & their photostabilization

Excessive exposure of UV radiation from the sunlight to human skin is dangerous and causes various skin disorders including skin cancer. Dermatologists worldwide recommend use of skin creams/lotions containing UV-filters/sunscreens for protection from such harmful effects. There is continuous evolution and development of new organic, inorganic and hybrid sunscreens which are being used in such skin care preparations. In the recent past it has been seen that some of these materials are not stable to UV light and the sun protection offered by them decreases rapidly with time. Therefore, most of the formulators now prefer photostable sunscreens or the formulations are designed in such a way that they provide inherent photostability.In this review, we have covered the chemistry of synthesis of different organic sunscreens, issues related to photostability of some of them, and different approaches used to enhance their photostability.     

Photostabilization of butyl methoxydibenzoylmethane (Avobenzone) and ethylhexyl methoxycinnamate by bis-ethylhexyloxyphenol methoxyphenyl triazine (Tinosorb S), a new UV broadband filter

It is now well documented that chronic UVA exposure induces damage to human skin. Therefore, modern sunscreens should not only provide protection from both UVB and UVA radiation but also maintain this protection during the entire period of exposure to the sun. UVA filters, however, are rare and not sufficiently photostable. We investigated the effect of the introduction of a new UV filter, bis-ethylhexyloxyphenol methoxyphenyl triazine (Tinosorb S), in oil in water sunscreen formulations on the photostability of butyl methoxydibenzoylmethane (Avobenzone [AVB]) after irradiation with an optically filtered Xenon arc source (UV irradiance adjusted at 1 mean effective dose [MED]/min). With spectrophotometrical methods to assess the sun protection factor (SPF) and UVA ratio and chromatographical methods to determine the amount of UV filters recovered after irradiation we showed that Tinosorb S prevented the photodegradation of AVB in a concentration-dependent way, leading to a sustained SPF and UVA ratio even after irradiation with doses of up to 30 MED. Since AVB was shown to destabilize ethylhexyl methoxycinnamate (EHM) we tested the effect of Tinosorb S in sunscreens containing this UV filter combination. Here too Tinosorb S showed photoprotective properties toward both UV filters. Thus, Tinosorb S can be used successfully to improve the photostability and efficiency of sunscreens containing AVB and EHM.     

Complexation of capsaicin with β-cyclodextrins to improve pesticide formulations: effect on aqueous solubility, dissolution rate, stability and soil adsorption

The binary systems of capsaicin (CP) and β-cyclodextrin (βCD) or hydroxypropyl-β-cyclodextrin (HPβCD) were investigated in an attempt to improve formulations of this pesticide. UV spectral shift methods indicated guest–host complex formation between CP and the two cyclodextrins (CDs). Phase solubility analysis showed B_s type diagrams with βCD, A_L type with HPβCD indicating the formation of an inclusion complex at 1:1 stoichiometric ratio in solution state. Solubility profiles indicated a 50-fold enhancement of CP solubility could be achieved in the presence of 60 mM HPβCD with respect to CP alone. Solid co-evaporated systems (CES) with 1:0.5–1:5 molar ratios of CP/CDs were physicochemically characterized, revealing that the true inclusion complexes could be formed in the solid CP/βCD systems with 1:5 molar ratio and in the solid CP/HPβCD systems with the molar ratios more than 1:3, respectively. In contrast, crystalline drug was detectable in all other systems. Compared with corresponding physical mixtures (PMs), the CES exhibited significant enhancement with regard to CP dissolution and the protection from CP degradation under the accelerated conditions. It was also revealed that complexation of CP with HPβCD had a pronounced improved effect on the pesticide formulations and greatly reduced the amount of CP adsorbed in the soil. These results demonstrate that HPβCD may be a preferred excipient, enabling more efficient and intelligent use of CP/CDs inclusion complexes in the development of pesticide formulations.     

p53 tumor suppressor gene: a critical molecular target for UV induction and prevention of skin cancer

The relationship between exposure to UV radiation and development of skin cancer has been well established. Several studies have shown that UVB induces unique mutations (C-->T and CC-->TT transitions) in the p53 tumor suppressor gene that are not commonly induced by other carcinogens. Our studies have demonstrated that UV-induced mouse skin cancers contain p53 mutations at a high frequency and that these mutations can be detected in UV-irradiated mouse skin well before the appearance of skin tumors. This observation suggested that it might be possible to use p53 mutations as a biologic endpoint for testing the efficacy of sunscreens in photoprotection studies. Indeed, application of SPF 15 sunscreens to mouse skin before each UVB irradiation resulted in reduction in the number of p53 mutations. Because p53 mutations represent an early essential step in photocarcinogenesis, these results imply that inhibition of this event may protect against skin cancer development. This hypothesis was confirmed by our finding that sunscreens used in p53 mutation inhibition experiments also protected mice against UVB-induced skin cancer.     

Human Hair as a Natural Sun Protection Agent: A Quantitative Study

The rising incidence of skin cancers attributable to excessive sun exposure has become a major health concern worldwide. While numerous studies have analyzed the sun protective effect of sunscreens, clothing and antioxidants, none to date have measured the photoprotective effect of hair, despite clinical evidence that individuals with balding or thinning hair are at greater risk of skin lesions that can progress to cancer, hence the recommendation to use hats or umbrellas. We analyzed the level of protection offered by hair according to hair density, thickness and color using the spectral transmittance and corrected for relative erythema effectiveness. Our results show that hair provides a barrier against both UVB and UVA radiation which is significantly increased with respect to the hair density, thickness and the presence of melanins. This is the first study to quantify sun protection factor offered by hair, namely hair ultraviolet protection factor (HUPF). We believe that hair should be recognized as an important natural sun barrier in the prevention of UV‐induced skin cancers.     

Antioxidative Responses of Two Marine Microalgae During Acclimation to Static and Fluctuating Natural UV Radiation

Photoacclimation properties were investigated in two marine microalgae exposed to four ambient irradiance conditions: static photosynthetically active radiation (PAR: 400–700 nm), static PAR + UVR (280–700 nm), dynamic PAR and dynamic PAR + UVR. High light acclimated cultures of Thalassiosira weissflogii and Dunaliella tertiolecta were exposed outdoors for a maximum of 7 days. Dynamic irradiance was established by computer controlled vertical movement of 2 L bottles in a water filled basin. Immediate (<24 h), short-term (1–3 days) and long-term (4–7 days) photoacclimation was followed for antioxidants (superoxide dismutase, ascorbate peroxidase and glutathione cycling), growth and pigment pools. Changes in UVR sensitivity during photoacclimation were monitored by measuring UVR-induced inhibition of carbon assimilation under standardized UV conditions using an indoor solar simulator. Both species showed immediate antioxidant responses due to their transfer to the outdoor conditions. Furthermore, upon outdoor exposure, carbon assimilation and growth rates were reduced in both species compared with initial conditions; however, these effects were most pronounced in D. tertiolecta . Outdoor UV exposure did not alter antioxidant levels when compared with PAR-only controls in both species. In contrast, growth was significantly affected in the static UVR cultures, concurrent with significantly enhanced UVR resistance. We conclude that antioxidants play a minor role in the reinforcement of natural UVR resistance in T. weissflogii and D. tertiolecta .     

Occupational UV Exposure of Environmental Agents in Valencia,Spain

Excessive exposure to ultraviolet radiation (UVR) is considered the most important environmental risk factor in the development of melanoma and skin cancer. Outdoor workers are among those with the highest risk from exposure to solar UVR, as their daily activities constantly expose them to this radiation source. A study was carried out in Valencia, Spain, in summer 2012 and involved a group of 11 workers for a period of six 2‐day recordings. Sensitive spore‐film filter‐type personal dosimeters (VioSpor) were used to measure erythemal UVR received by environmental agents in the course of their daily work. Median 2‐day UV exposure was 6.2 standard erythema dose (SED), with 1 SED defined as effective 100 J m^?2 when weighted with the Commission Internationale de L′Eclairage's (CIE) erythemal response function. These workers were found to receive a median of 8.3% total daily ambient ultraviolet erythemal radiation. Comparison with the occupational UV exposure limit showed that the subjects had received an erythemal UV dose in excess of occupational guidelines, indicating that protective measures against this risk are highly advisable.     

Analysis of Compact Fluorescent Lights for Use by Patients with Photosensitive Conditions

Ultraviolet radiation (UVR) is hazardous to patients with photosensitive skin disorders, such as lupus erythematosus, xeroderma pigmentosum and skin cancer. As such, these patients are advised to minimize their exposure to UVR. Classically, this is accomplished through careful avoidance of sun exposure and artificial tanning booths. Indoor light bulbs, however, are generally not considered to pose significant UVR hazard. We sought to test this notion by measuring the UV emissions of 19 different compact fluorescent light bulbs. The ability to induce skin damage was assessed with the CIE erythema action spectrum, ANSI S(λ) generalized UV hazard spectrum and the CIE photocarcinogenesis action spectrum. The results indicate that there is a great deal of variation amongst different bulbs, even within the same class. Although the irradiance of any given bulb is low, the possible daily exposure time is rather lengthy. This results in potential daily UVR doses ranging from 0.1 to 625 mJ cm⁻², including a daily UVB (290–320 nm) dose of 0.01 to 15 mJ cm⁻². Because patients are exposed continually over long time frames, this could lead to significant cumulative damage. It would therefore be prudent for patients to use bulbs with the lowest UV irradiance.     

Measurements of the Protective Effect of Topically Applied Sunscreens using in vitro Three-dimensional Dermal and Skin Equivalents

Abstract— For preventing or minimizing acute and chronic skin damage caused by UV radiation, the use of sunscreens is probably the most important measure. To screen the protective efficacy of new sunscreen molecules or formulations against UV rays, we evaluated as in vitro testing methods the use of two three-dimensional models, a dermal equivalent (DE) and a skin equivalent (SE). The DE is composed of a porous collagen-glycosaminoglycans-chitosan matrix populated by normal human fibroblasts. The SE is comprised of a fully differentiated epidermis realized by seeding keratinocytes onto the DE. In this study, we demonstrated that the DE and SE models react to the deleterious effects of UVA and UVB. Then, we extended our research to the evaluation of their usefulness for photoprotection trials. Sunscreen agents (Euso-lex 8020 and 6300) and commercially available sunscreens (chemical and physical filter formulations) that protect the skin against either UVA or UVB were evaluated. The tested products were applied (n = 6) topically (10 μL) and incubated for 30 min prior to irradiation over a range of UVA (0-50 J/cm²) or UVB (0-5 J/cm²). The photoprotection provided by the tested sunscreen molecules and formulations was evaluated by measurement of residual cellular viability 24 h postirradiation using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetra-zolium bromide (MTT) test and assessment of the inflammation response by interleukin-la release assay. When sunscreens were applied prior to UV exposure, a higher residual cellular viability versus control was obtained, demonstrating the photoprotective effects of the tested products. These in vitro models could be used for screening tests to evaluate the protective effects of sunscreen molecules and formulations, especially for UVA trials because there is a lack of consensus for an in vivo method.     

Study on the Supramolecular Inclusion Complex of β-Cyclodextrin/Lappaconitine

Lappaconitine (Lap) is a diterpenoid akaliamide, naturally occurring in roots and rhizomes of Aconitum and delphinium. Lap reveals bradycardic, hypotensive, antinocieptive activity. However, its application is restrained owing to its poor water solubility, toxicity and side effects on humans. In a number of pharmaceutical studies,CDs have been reported to interact with many drug molecules to form inclusion complexes. These inclusion complexes have been extensively used to improve water solubility of poorly soluble drugs, to reduce their toxicity, and to increase the dissolution rate [1]. In the present work, the β-CD/Lap complex was prepared by kneading method. The products have been characterized by the solubility measurement as well as UV, FTIR, NMR spectroscopy and X-ray powder diffractometry.     

DUAL ROLE OF MELANINS AND MELANIN PRECURSORS AS PHOTOPROTECTIVE AND PHOTOTOXIC AGENTS: INHIBITION OF ULTRAVIOLET RADIATION-INDUCED LIPID PEROXIDATION

Ultraviolet radiation (UVR) is one of the risk factors for skin cancer and the main inducer of melanin pigmentation, the major protective mechanism of mammalian skin against radiation damage. The melanin pigments, eumelanin and pheomelanin, are likely to be important in protection against UVR, but their precursors are generally considered as phototoxic. The available data suggest DNA damage as the mechanism of phototoxicity. However, the effect of melanin precursors on membrane damage through lipid peroxidation, another important and probably more relevant (from the point-of-view of the melanosomal confinement of these molecules) mechanism of phototoxicity, is not known. As a model system for UVR–melanin–membrane interactions, we irradiated liposomes in the presence of eumelanin, pheomelanin and two of their major precursors, 5,6-dihydroxyindole (DHI) and 5-S-cysteinyldopa (SCD). The presence of the two melanin precursors substantially reduced the formation of lipid peroxidation products resulting from UVR exposure. The antioxidant activity of the melanin precursors was diminished under strong prooxidant conditions (presence of Fe³⁺). These results suggest that melanin precursors may have an important role in the protection of skin against the harmful effects of UVR including photocarcinogenesis.     

An Approach to Minimize Tumour Proliferation by Reducing the Formation of Components for Cell Membrane

Isoprenoids are natural compounds essential for a great number of cellular functions. One of them is farnesol (FOH), which can reduce cell proliferation, but its low solubility in aqueous solvents limits its possible clinical use as a pharmacological tool. One alternative is the use of cyclodextrins (CDs) which house hydrophobic molecules forming inclusion complexes. To assess FOH potential application in anticancer treatments, Sulfobutylated β-cyclodextrin Sodium Salt (SBE-β-CD) was selected, due to it has high solubility, approbation by the FDA, and numerous studies that ensure its safety to be administered parenterally or orally without nephrotoxicity associated. The therapeutic action of farnesol and complex were studied in different carcinoma cells, compared with a normal cell line. Farnesol showed selectivity, affecting the viability of colon and liver cancer cells more than in breast cancer cells and fibroblasts. All cells suffered apoptosis after being treated with 150 μM of free FOH, but the complex reduced their cell viability between 50 and 75%. Similar results were obtained for both types of isomers, and the addition of phosphatidylcholine reverses this effect. Finally, cell cycle analysis corroborates the action of FOH as inducer of a G0/G1 phase; when the cells were treated using the complex form, this viability was reduced, reaching 50% in the case of colon and liver, 60% in fibroblasts, and only 75% in breast cancer.     

环糊精包结物包结比的测定

由于环糊精具有“外亲水,内疏水”的独特性质,它可以包结许多物质而形成主客体配合物,从而改变物质的特性,所以被广泛应用于各行各业中,包结物的包结比是决定包络物性质的一个重要参数,在查阅大量文献的基础上,总结出环糊精包结反应过程中测定主客体间的包结比的方法,并对其进行了较详细的介绍。     

Angiotensin converting enzyme inhibitors/cyclodextrin inclusion complexes: solution and solid-state characterizations and their thermal stability

Angiotensin converting enzyme (ACE) inhibitors have recently gained attention as a new class of drug in the therapeutic management of glaucoma. However, the application of eye drops is limited because of their chemical instability in aqueous solutions. To overcome such a problem, cyclodextrins (CDs) were introduced to form inclusion complexes. Three ACE inhibitors, namely, captopril, quinapril and fosinopril (FOS), were chosen and the effect of CDs on their thermal stability in aqueous solutions was investigated. All three drugs formed inclusion complexes of 1:1 stoichiometry with all three natural CDs and the FOS/γCD inclusion complex possessed the highest stability constant, resulting in thermal stability enhancement. Furthermore, the addition of antioxidants could greatly enhance the thermal stability of FOS in the presence of γCD in aqueous solutions. The inclusion complex formation of FOS/γCD was further examined by computational and experimental characterizations. All these characterization results confirmed that FOS and γCD formed a true inclusion complex that provided drug stabilization in the aqueous eye drop medium.

     

Topical emulgel formulation containing inclusion complex of calcipotriol with cyclodextrin

Psoriasis is a relatively common, chronic, inflammatory disease that affects the skin, scalp, and joints. Calcipotriol is one of the most commonly used topical agents for the treatment of psoriasis. However, it is a water-insoluble active substance and frequently leads to skin irritation in patients. Cyclodextrins (CDs) are cyclic oligosaccharides consisting of (α-1,4-)-linked d-glucopyranose units. CD molecules have a hydrophilic outer surface and a lipophilic central cavity, and they are able to form inclusion complexes in aqueous solutions with many drugs. They can increase bioavailability, aqueous solubility, and stability and also reduce the side effects of the drugs. The aim of this study was to develop a new topical drug delivery system of calcipotriol in order to improve the solubility and dissolution characteristics of the drug and reduce the undesirable side effects. For this purpose, an inclusion complex of calcipotriol with Captisol^® was prepared, and complex formation was confirmed. The inclusion complex and pure drug were formulated separately in an emulgel base. Dissolution profiles of calcipotriol from emulgel formulations were compared with a commercial product of the drug. The drug release was significantly increased with the emulgel formulations compared to the commercial cream product.