In vitro Percutaneous Absorption and in vivo Stratum Corneum Distribution of an Organic and a Mineral Sunscreen

Centre de Recherche Pierre Fabre, Tolosa de Llenguadoc, Midi-Pyrénées, France
Skin pharmacology and physiology (Impact Factor: 2.37). 02/2007; 20(1):10-20. DOI: 10.1159/000096167
Source: PubMed


Sunscreens, whose main function is to protect the skin against the harmful effects of solar irradiation, should remain at the skin surface or impregnate the first layers of the stratum corneum only and not penetrate into the underlying living tissue. The goal of this work was to assess the penetration of titanium dioxide (TiO(2)) and methylene bis-benzotriazoyl tetramethylbutylphenol (MBBT), included in a broad-spectrum sunscreen formulation, into human skin in vivo, using the tape stripping method, and in vitro, using a compartmental approach. An additional objective was to propose an easy and minimally invasive approach to determining the percutaneous uptake of sunscreens following topical application. TiO(2) and MBBT were quantified using colorimetric assay and HPLC analysis, respectively. The transmission electron microscopy and particle-induced X-ray emission techniques were used to localize the TiO(2) in skin sections. More than 90% of both sunscreens was recovered in the first 15 tape strippings. In addition we have shown that the remaining 10% did not penetrate the viable tissue, but was localized in the furrows and in the opened infundibulum. Less than 0.1% of MBBT was detected in the receptor medium, and no TiO(2) was detected in the follicle, viable epidermis or dermis. Thus, this in vivo and in vitro penetration study showed an absence of TiO(2) penetration into the viable skin layers through either transcorneal or transfollicular pathways and negligible transcutaneous absorption of MBBT. However, differences in distribution within the stratum corneum reinforced the need for a complementary approach, using minimally invasive in vivo methodology and in vitro compartmental analysis. This combination represents a well-adapted method for testing the safety of topically applied sunscreen formulations in real-life conditions.

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Available from: Alain Mavon, Sep 10, 2015
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    • "However, cutaneous penetration is a critical issue regarding the development of sunscreens containing antioxidants. UV-filters must remain in the stratum corneum to be safe and effective (Mavon et al., 2007; Yang et al., 2008). On the other hand antioxidant compounds should be able to reach viable skin layers to afford satisfactory photoprotection, since UV radiation penetrates deeply into the skin (Saija et al., 2000). "
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    ABSTRACT: Cutaneous permeation is a critical parameter when topical application of sunscreens containing antioxidants is considered. The aim of this study was to evaluate the cutaneous penetration of most marketed UV-filters combined with trans-resveratrol (RES) and beta-carotene (BTC) since few studies report skin penetration when such compounds are applied. Formulations containing octocrylene, octyl methoxycinnamate, avobenzone and bemotrizinole were prepared and supplemented or not with BTC, or with RES, or with both compounds in combination. Penetration studies were performed using Franz vertical diffusion cells and porcine ear skin as the biological membrane. The quantification of UV-filters and antioxidants in the stratum corneum (SC), viable epidermis plus dermis and receptor fluid was performed by HPLC. Results suggested that UV-filters and antioxidants did not permeate the skin but were retained for 12h post application. About 90% and 80%, respectively, of the total penetrated amount of UV-filters and antioxidants was found in the SC. Interestingly, it was observed that BTC, alone or combined with RES, reduced the skin retention of UV-filters on average by 63%. In conclusion, this study demonstrated that the combination of antioxidants and UV-filters in sunscreens is advantageous for cutaneous penetration, since BTC and BTC+RES improved sunscreen safety by reducing delivery of the four UV-filters in the study into SC and viable epidermis. Copyright © 2015. Published by Elsevier B.V.
    International Journal of Pharmaceutics 02/2015; 484(1-2). DOI:10.1016/j.ijpharm.2015.02.062 · 3.65 Impact Factor
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    • "Considerable work has focused on TiO 2 and ZnO NPs, which are commonly formulated into ultraviolet radiation (UVR) protective sunscreens and cosmetics products. Studies of barrier intact skin, employing numerous human and animal skin models, generally report no significant evidence for ZnO or TiO 2 NP penetration beyond the stratum corneum (Cross et al. 2007; Tan et al. 1996; Gamer et al. 2006; Schulz et al. 2002; Lademann et al. 1999; Mavon et al. 2007; Pflucker et al. 1999; Roberts et al. 2008; Schulz et al. 2002; Wu et al. 2009; Zvyagin et al. 2008). Much less is understood, however, about how UVR skin exposure may modulate the susceptibility to NP stratum corneum penetration and systemic transport. "
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    ABSTRACT: Abstract Ultraviolet radiation (UVR) skin exposure is a common exogenous insult that can alter skin barrier and immune functions. With the growing presence of nanoparticles (NPs) in consumer goods and technological applications the potential for NPs to contact UVR exposed skin is increasing. Therefore it is important to understand the effect of UVR on NP skin penetration and potential for systemic translocation. Previous studies qualitatively showed that UVR skin exposure can increase the penetration of NPs below the stratum corneum. In the present work, an in vivo mouse model was used to quantitatively examine the skin penetration of carboxylated (CdSe/ZnS, core/shell) quantum dots (QDs) through intact and UVR barrier disrupted murine skin by organ Cd mass analysis. Transepidermal water loss was used to measure the magnitude of the skin barrier defect as a function of dose and time post UVR exposure. QDs were applied to mice 3-4 days post UVR exposure at the peak of the skin barrier disruption. Our results reveal unexpected trends that suggest these negative charged QDs can penetrate barrier intact skin and that penetration and systemic transport depends on the QD application time post UVR exposure. The effect of UVR on skin resident dendritic cells and their role in the systemic translocation of these QDs are described. Our results suggest that NP skin penetration and translocation may depend on the specific barrier insult and the inflammatory status of the skin.
    Nanotoxicology 10/2012; DOI:10.3109/17435390.2012.741726 · 6.41 Impact Factor
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    • "Dussert and Gooris (1997) studied water/oil (w/o) emulsions of TiO 2 and ZnO on excised human skin and found that the emulsion remained on the surface of the SC; however, TiO 2 /ZnO formulations (80–200 nm, up to 1 lm) applied to in vitro porcine skin for 24 h showed no penetration (Gamer et al., 2006). Absorption studies with in vitro and in vivo human skin (20 nm TiO 2 in a w/o emulsion for 5 h) showed no penetration into the viable epidermal layers (Mavon et al., 2007). TiO 2 oil/water (o/w) emulsions applied to in vitro human organotypic cultures for 24 h and to in vivo human forearms for 6 h (Bennat and Müller-Goymann, 2000) showed that penetration was greater in vitro than in vivo, but TiO 2 tape stripping indicated that particles remained within SC layers. "
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    ABSTRACT: Sunscreens containing titanium dioxide (TiO(2)) and zinc oxide (ZnO) nanoparticles (NP) are effective barriers against ultraviolet B (UVB) damage to skin, although little is known about their disposition in UVB-damaged skin. Pigs were exposed to UVB that resulted in moderate sunburn. For in vitro studies, skin in flow-through diffusion cells were treated 24 h with four sunscreen formulations as follows: 10% coated TiO(2) in oil/water (o/w), 10% coated TiO(2) in water/oil (w/o), 5% coated ZnO in o/w, and 5% uncoated ZnO in o/w. TiO(2) (rutile, crystallite) primary particle size was 10 × 50 nm with mean agglomerates of 200 nm (range ca. 90 nm--460 nm); mean for ZnO was 140 nm (range ca. 60--200 nm). Skin was processed for light microscopy, scanning (SEM) and transmission electron microscopy (TEM), and time-of-flight secondary ion mass spectrometry (TOF-SIMS). UVB-exposed skin had typical sunburn histology. TEM showed TiO(2) NP 17 layers into stratum corneum (SC), whereas ZnO remained on the surface. TOF-SIMS showed TiO(2) and ZnO epidermal penetration in both treatments. Perfusate analyzed by TEM/energy dispersive x-ray spectroscopy or inductively coupled plasma mass spectrometry detected no Ti or Zn, indicating minimal transdermal absorption. In vivo, skin was dosed at 24 h occluded with formulations and at 48 h. TiO(2) NP in o/w formulation penetrated 13 layers into UVB-damaged SC, whereas only 7 layers in normal skin; TiO(2) in w/o penetrated deeper in UVB-damaged SC. Coated and uncoated Zn NP in o/w were localized to the upper one to two SC layers in all skin. By SEM, NP were localized as agglomerates in formulation on the skin surface and base of hair. TOF-SIMS showed Ti within epidermis and superficial dermis, whereas Zn was limited to SC and upper epidermis in both treatments. In summary, UVB-damaged skin slightly enhanced TiO(2) NP or ZnO NP penetration in sunscreen formulations but no transdermal absorption was detected.
    Toxicological Sciences 06/2011; 123(1):264-80. DOI:10.1093/toxsci/kfr148 · 3.85 Impact Factor
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