Turmeric, derived from the plant Curcuma longa, is a gold-colored spice commonly used in the Indian subcontinent, not only for health care but also for the preservation of food and as a yellow dye for textiles. Curcumin, which gives the yellow color to turmeric, was first isolated almost two centuries ago, and its structure as diferuloylmethane was determined in 1910. Since the time of Ayurveda (1900 Bc) numerous therapeutic activities have been assigned to turmeric for a wide variety of diseases and conditions, including those of the skin, pulmonary, and gastrointestinal systems, aches, pains, wounds, sprains, and liver disorders. Extensive research within the last half century has proven that most of these activities, once associated with turmeric, are due to curcumin. Curcumin has been shown to exhibit antioxidant, anti-inflammatory, antiviral, antibacterial, antifungal, and anticancer activities and thus has a potential against various malignant diseases, diabetes, allergies, arthritis, Alzheimer's disease, and other chronic illnesses. These effects are mediated through the regulation of various transcription factors, growth factors, inflammatory cytokines, protein kinases, and other enzymes. Curcumin exhibits activities similar to recently discovered tumor necrosis factor blockers (e.g., HUMIRA, REMICADE, and ENBREL), a vascular endothelial cell growth factor blocker (e.g., AVASTIN), human epidermal growth factor receptor blockers (e.g., ERBITUX, ERLOTINIB, and GEFTINIB), and a HER2 blocker (e.g., HERCEPTIN). Considering the recent scientific bandwagon that multitargeted therapy is better than monotargeted therapy for most diseases, curcumin can be considered an ideal "Spice for Life".

Curcumin: The Indian solid gold

Manmade nanoparticles range from the well-established multi-ton production of carbon black and fumed silica for applications in plastic fillers and car tyres to microgram quantities of fluorescent quantum dots used as markers in biological imaging. As nano-sciences are experiencing massive investment worldwide, there will be a further rise in consumer products relying on nanotechnology. While benefits of nanotechnology are widely publicised, the discussion of the potential effects of their widespread use in the consumer and industrial products are just beginning to emerge. This review provides comprehensive analysis of data available on health effects of nanomaterials.

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Nanoparticles – known and unknown health risks

During the last few years, research on toxicologically relevant properties of engineered nanoparticles has increased tremendously. A number of international research projects and additional activities are ongoing in the EU and the US, nourishing the expectation that more relevant technical and toxicological data will be published. Their widespread use allows for potential exposure to engineered nanoparticles during the whole lifecycle of a variety of products. When looking at possible exposure routes for manufactured Nanoparticles, inhalation, dermal and oral exposure are the most obvious, depending on the type of product in which Nanoparticles are used. This review shows that (1) Nanoparticles can deposit in the respiratory tract after inhalation. For a number of nanoparticles, oxidative stress-related inflammatory reactions have been observed. Tumour-related effects have only been observed in rats, and might be related to overload conditions. There are also a few reports that indicate uptake of nanoparticles in the brain via the olfactory epithelium. Nanoparticle translocation into the systemic circulation may occur after inhalation but conflicting evidence is present on the extent of translocation. These findings urge the need for additional studies to further elucidate these findings and to characterize the physiological impact. (2) There is currently little evidence from skin penetration studies that dermal applications of metal oxide nanoparticles used in sunscreens lead to systemic exposure. However, the question has been raised whether the usual testing with healthy, intact skin will be sufficient. (3) Uptake of nanoparticles in the gastrointestinal tract after oral uptake is a known phenomenon, of which use is intentionally made in the design of food and pharmacological components. Finally, this review indicates that only few specific nanoparticles have been investigated in a limited number of test systems and extrapolation of this data to other materials is not possible. Air pollution studies have generated indirect evidence for the role of combustion derived nanoparticles (CDNP) in driving adverse health effects in susceptible groups. Experimental studies with some bulk nanoparticles (carbon black, titanium dioxide, iron oxides) that have been used for decades suggest various adverse effects. However, engineered nanomaterials with new chemical and physical properties are being produced constantly and the toxicity of these is unknown. Therefore, despite the existing database on nanoparticles, no blanket statements about human toxicity can be given at this time. In addition, limited ecotoxicological data for nanomaterials precludes a systematic assessment of the impact of Nanoparticles on ecosystems.

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The potential risks of nanomaterials: a review carried out for ECETOC

Lipid nanoparticles (SLN, NLC) in cosmetic and pharmaceutical dermal products.

Sunscreens are used to provide protection against adverse effects of ultraviolet (UV)B (290-320 nm) and UVA (320-400 nm) radiation. According to the United States Food and Drug Administration, the protection factor against UVA should be at least one-third of the overall sun protection factor. Titanium dioxide (TiO2) and zinc oxide (ZnO) minerals are frequently employed in sunscreens as inorganic physical sun blockers. As TiO2 is more effective in UVB and ZnO in the UVA range, the combination of these particles assures a broad-band UV protection. However, to solve the cosmetic drawback of these opaque sunscreens, microsized TiO2 and ZnO have been increasingly replaced by TiO2 and ZnO nanoparticles (NPs) (<100 nm). This review focuses on significant effects on the UV attenuation of sunscreens when microsized TiO2 and ZnO particles are replaced by NPs and evaluates physicochemical aspects that affect effectiveness and safety of NP sunscreens. With the use of TiO2 and ZnO NPs, the undesired opaqueness disappears but the required balance between UVA and UVB protection can be altered. Utilization of mixtures of micro- and nanosized ZnO dispersions and nanosized TiO2 particles may improve this situation. Skin exposure to NP-containing sunscreens leads to incorporation of TiO2 and ZnO NPs in the stratum corneum, which can alter specific NP attenuation properties due to particle-particle, particle-skin, and skin-particle-light physicochemical interactions. Both sunscreen NPs induce (photo)cyto- and genotoxicity and have been sporadically observed in viable skin layers especially in case of long-term exposures and ZnO. Photocatalytic effects, the highest for anatase TiO2, cannot be completely prevented by coating of the particles, but silica-based coatings are most effective. Caution should still be exercised when new sunscreens are developed and research that includes sunscreen NP stabilization, chronic exposures, and reduction of NPs' free-radical production should receive full attention.

https://www.dovepress.com/getfile.php?fileID=11179

Titanium dioxide and zinc oxide nanoparticles in sunscreens: focus on their safety and effectiveness

Nanoparticles--an efficient carrier for drug delivery into the hair follicles.

Background/purpose: Porcine ear skin is used in studies of percutaneous penetration as a substitute for human skin. The structure of this tissue, including hair follicles, was studied qualitatively and quantitatively in comparison with human skin.

Methods: Sections of shock-frozen biopsies, biopsies embedded in paraffin and cyanoacrylate skin surface biopsies were investigated using microscopy. The thickness of the different skin layers and the follicular characteristics were determined.

Results: The thickness of the stratum corneum was 17–28 μm, whereas the viable epidermis was 60–85 μm thick. On 1 cm2, 11–25 hairs were detected, showing a diameter of 58–97 μm and a maximal extension depth of 0.96–1.38 mm into the skin. The orifices of the porcine infundibula showed a diameter of approximately 200 μm.

Conclusions: The results obtained are similar to those of human skin, indicating the suitability of this porcine tissue as a model for human skin.

Porcine ear skin: an in vitro model for human skin

Nanoparticles represent an important drug carrier system. Recently, we have reported on the penetration and storage behavior of particular and non-particular substances revealing the superiority of pa

Hair follicles - a long-term reservoir for drug delivery.

What is already known about this subject

• In recent years, it has been suggested that hair follicles represent important shunt routes into the skin for drugs and chemicals [1–3].

• In vitro studies have shown the importance of skin appendages for skin penetration by hydrophilic compounds [4]. Investigation of follicular penetration in vivo has been difficult due to the absence of appropriate analytical methods or suitable animal model systems.

• Recently, a new method was described that quantifies follicular penetration in vivo by using selective closure of hair follicles [5].

• Caffeine is frequently used in skin penetration experiments as a model for highly water-soluble compounds. Occlusion [6] and skin thickness [7] seem to have little influence on the penetration of caffeine. However, percutaneous absorption rates for caffeine exhibit regional skin differences in humans in vivo[1].

What this study adds

• The results of the present study demonstrate that a fast drug delivery of caffeine occurs through shunt routes. Therefore, hair follicles are considerable weak spots in our protective sheath against penetration into the body by hydrophilic substances.

• We showed that there is a quantitative distinction between follicular penetration and interfollicular diffusion of caffeine in vivo.

• These findings are of importance for the development and optimization of topically applied drugs and cosmetics. In addition, such properties must be considered in the development of skin protection measures.

Aims
The skin and its appendages are our protective shield against the environment and are necessary for the maintenance of homeostasis. Hypotheses concerning the penetration of substances into the skin have assumed diffusion through the lipid domains of the stratum corneum. It is believed that while hair follicles represent a weakness in the shield, they play a subordinate role in the percutaneous penetration processes. Previous investigation of follicular penetration has mostly addressed methodical and technical problems. Our study utilized a selective closure technique of hair follicle orifices in vivo, for the comparison of interfollicular and follicular absorption rates of caffeine in humans.

Methods
Every single hair follicle within a delimited area of skin was blocked with a microdrop of a special varnish-wax-mixture in vivo. Caffeine in solution was topically applied and transcutaneous absorption into the blood was measured by a new surface ionization mass spectrometry (SI/MS) technique, which enabled a clear distinction to be made between interfollicular and follicular penetration of a topically applied substance.

Results
Caffeine (3.75 ng ml−1) was detected in blood samples, 5 min after topical application, when the follicles remained open. When the follicles were blocked, caffeine was detectable after 20 min (2.45 ng ml−1). Highest values (11.75 ng caffeine ml−1) were found 1 h after application when the follicles were open.

Conclusions
Our findings demonstrate that hair follicles are considerable weak spots in our protective sheath against certain hydrophilic drugs and may allow a fast delivery of topically applied substances.

/pdf/the-role-of-hair-follicles-in-the-percutaneous-absorption-of-34gx1qee3v.pdf

The role of hair follicles in the percutaneous absorption of caffeine

The influence of specific follicle properties, sebum production and hair growth on the follicular penetration of topically applied substances was investigated. The behavior of follicles identified in selected skin areas of volunteers was analyzed by various tape stripping and staining methods in combination with laser scanning microscopy. Furthermore hair growth in the selected skin areas was determined. A correlation between sebum production, hair growth activity and follicular penetration was observed.

Nina Otberg

Papers

Nanoparticles--an efficient carrier for drug delivery into the hair follicles.

Porcine ear skin: an in vitro model for human skin

Hair follicles - a long-term reservoir for drug delivery.

The role of hair follicles in the percutaneous absorption of caffeine

Investigation of Follicular Penetration of Topically Applied Substances