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Clinical Evaluation of Fullerene-C(60) Dissolved in Squalane for Anti-Wrinkle Cosmetics
Abstract
Highly purified and organic solvent-free fullerene-C60 was dissolved, at nearly saturated concentration of 278 ppm, in squalane prepared from olive oil, which is designated as LipoFullerene (LF-SQ) and was examined for usage as a cosmetic ingredient with antioxidant ability. The aim of this study was to assess the anti-wrinkle formation efficacy of LF-SQ in subjects. A total of 23 Japanese women (group I: age 38.9 +/- 3.8, n = 11, group II; age 39.4 +/- 4.3, n = 12) were enrolled in an 8-week trial of LF-SQ blended cream in a randomized, matched pair double-blind study. The LF-SQ cream was applied twice daily on the right or left half of the face, and squalane blended cream (without fullerene-C60) was applied as the placebo on another half of the face. As clinical evaluations of wrinkle grades, visual observation and photographs, and silicone replicas of both crow's feet areas were taken at baseline (0 week) and at 4th and 8th weeks. Skin replicas were analyzed using an optical profilometry technique. The wrinkle and skin-surface roughness features were calculated and statistically analyzed. Subsequently, trans-epidermal water loss (TEWL), moisture levels of the stratum corneum, and visco-elasticity (suppleness: RO and elasticity: R7) were measured on cheeks by instrumental analysis. LF-SQ cream enhanced the skin moisture and the anti-wrinkle formation. LF-SQ cream that was applied on a face twice daily was not effective at 4th week, but significantly more effective than the placebo at 8th week (p < 0.05) without severe side effects. The roughness-area ratio showed significant improvement (p < 0.05) at 8th week with LF-SQ cream as compared to 0 week with LF-SQ cream, but no significant difference was detected between LF-SQ cream and the placebo. We suggest that LF-SQ could be used as an active ingredient for wrinkle-care cosmetics.
... There are already some fullerene-containing cosmetics on the market. In addition, researchers have conducted some clinical trials on fullerene-containing cosmetics [256,257]. For example, Kato et al conducted a clinical evaluation of [60]fullerene dissolved in squalene for anti-wrinkle cosmetics in 2010. ...
... For example, Kato et al conducted a clinical evaluation of [60]fullerene dissolved in squalene for anti-wrinkle cosmetics in 2010. They conducted continuous tests on the skin condition of 23 young or middle-aged women who used the lipofullerene-containing skin cream LF-SQ twice a day in the morning and evening [257]. The result showed that, compared with the placebo group, the continuous use of LF-SQ for eight weeks could significantly reduce the area of wrinkles [257]. ...
... They conducted continuous tests on the skin condition of 23 young or middle-aged women who used the lipofullerene-containing skin cream LF-SQ twice a day in the morning and evening [257]. The result showed that, compared with the placebo group, the continuous use of LF-SQ for eight weeks could significantly reduce the area of wrinkles [257]. In addition, there are some reports that fullerene and their derivatives can be used as hair growth agents to induce the production of new hair follicles [258]. ...
... 44 Numerous studies have pointed out the protective effect of olive tree compounds on skin ageing, thanks to their role in the various mechanisms involved in the ageing process. [45][46][47] These compounds include squalene (Sq) from olives or their derivatives. In an in vitro test with HaCat keratinocytes, Kato et al. 45 observed a significant reduction in oxidative stress, an increase in cell viability, and a reduction in histological alterations in a 3D human skin model, which could translate into a protective effect against the appearance of signs of ageing. ...
... Both treatments reduced the area and depth of wrinkles, although not significantly, and increased skin hydration. 47 In terms of adverse effects, no cases of toxicity were reported, probably due to the fact that these products are not able to reach the dermal venous circulation. 48 In the same vein, Wanitphakdeedecha et al. 49 described that the use of a facial cream enriched with olive leaf extract promotes facial rejuvenation by decreasing transepidermal water loss and wrinkles and improving hydration. ...
... Significant improvement of the roughness-area ratio. 47 ...
The olive tree and its derivatives are of great interest in the field of biomedicine due to their numerous health properties. The aim of the present study was to identify the effects of the use of olive products, extra virgin olive oil (EVOO) and products derived from its extraction, on the skin. Numerous studies have pointed out the protective effect of olive compounds on skin ageing, thanks to their role in the different mechanisms involved in the ageing process, such as reducing oxidative stress, increasing cell viability and decreasing histological alterations. With regard to their photoprotective effect, the olive tree and its fruit contain phenolic compounds which have a protective effect against radiation, such as low ultraviolet absorption and high antioxidant activity, acting as a protective factor against photocarcinogenesis. Similarly, the anti-tumour effects of olives have been studied at the level of the different compounds and extracts obtained from them, and their ability to selectively attack human melanoma cells has been observed. They have also shown antibacterial activity against microorganisms particularly implicated in skin infections, such as Escherichia coli, Candida albicans, Staphylococcus aureus, Staphylococcus epidermidis, Enterococcus faecalis, Pseudomonas aeruginosa and Proteus spp. Likewise, on healthy tissue, they have shown the ability to stimulate growth, migration and the expression of genes involved in cell differentiation, which favours the regeneration of skin wounds. According to the results included in this review, the olive tree and its derivatives could be useful in the treatment of many skin conditions.
... 17 Several experimental studies of the permeation/interaction of fullerene and its derivatives with human and animal skin have been reported. [18][19][20][21][22][23][24][25][26][27][28] Rouse et al. performed the in vitro release of fullerene-based amino acid solutions through human epidermal keratinocytes (HEK) at different concentrations in the range of 0.00004-0.4 mg mL −1 at 37°C. ...
... 20 The authors also studied the antiwrinkle properties of LF-SQ on skin and showed that LF-SQ could be used as an active ingredient in wrinkle care cosmetics. 21 Aoshima et al. reported the effect of highly purified fullerenes (HPFs), which are used as antioxidants in the cosmetic industry, on human skin. It was shown that HPFs did not induce primary or cumulative skin irritation, skin sensitization, skin photosensitization or contact phototoxicity. ...
... Experimentally, it has also been shown that fullerenes penetrated into the deeper layers of porcine and human skin. [18][19][20][21] Earlier MD simulations also reported the spontaneous permeation of a single fullerene molecule through a cell membrane. 31,32,35,36 Ekkabut et al. performed coarse-grained MD simulations of the penetration of both single and cluster fullerenes through a 1,2-distearoyl-snglycero-3-phosphocholine (DPPC) bilayer. ...
The molecular level permeation mechanism of fullerenes and its derivatives through human skin could open a vast area for designing novel nanoparticles for cosmetics and drug delivery applications. In this study, we report the permeation mechanism of pristine fullerene C60 for the first time through the skin lipid layer, as determined via prolonged unconstrained and constrained coarse-grained molecular dynamics simulations. The skin layer was modelled as an equimolar ratio of ceramides, cholesterol and free fatty acids. It was observed that at lower concentrations fullerenes formed small clusters (3 or 5 molecules) in the aqueous phase, which further spontaneously permeated inside the bilayer and remained dispersed inside the bilayer interior. On the other hand, at higher concentrations fullerenes aggregated in the aqueous layer, penetrated in that form and remained aggregated in the bilayer interior. Lower concentrations of fullerenes did not induce significant structural changes in the bilayer, whereas at higher concentrations undulations were observed. The permeability of fullerene molecules was found to be concentration-dependent and was explained in terms of their free energy of permeation (thermodynamics) and diffusivity (dynamics). On the basis of the aggregation and dispersion of fullerenes, an optimum fullerene concentration was determined, which could be used for drug delivery and cosmetic applications.
... Fullerene derivatives (22,23) and dendrimers (24,25) are supramolecular structures with dimension of few nanometers and therefore can be considered as nanoparticles. Fullerenes have been investigated for their ability to absorb UV light and their radical scavenging properties (22,23). ...
... Fullerene derivatives (22,23) and dendrimers (24,25) are supramolecular structures with dimension of few nanometers and therefore can be considered as nanoparticles. Fullerenes have been investigated for their ability to absorb UV light and their radical scavenging properties (22,23). Dendrimers were first synthesised in 1978 and are essentially nano-sized. ...
... Obtained results showed that LipoFullerene could be used as an active ingredient for wrinkle-care cosmetics. (23). ...
This review has overviewed the nanotechnology approaches and safety concerns in cosmetics. Nanotechnology based nanomaterials have been widely use in cosmetics for recent few years such as in sunscreens, hair products, skincare products, etc. However debate on their definition and insufficient quantification methods are major problems still occur in the nanomaterial field. Moreover the frequent use of cosmetics, safety of nanoscale ingredients of them has gain importance mainly by means of their dermal exposure. Although the proposed benefits that may occur by incorporating nanoparticles in cosmetics are increased efficiency, transparency, unique texture, protection of active ingredient, and overall higher consumer compliance, there still have not enough studies proved whether they are completely safe or not. As a conclusion major issues related nanomaterials such as developing, using and researching is going to increase in the near future due to their economically importance.
... citronellol (1.8%À7.2%), nerol (0.2%À4.2%), geraniol (0.9%À7.0%), along with rose oxides [187]. Rose extract provides anti-aging effects to the skin and so is believed to nourish and improve skin tone and rejuvenate the skin. ...
... Fullerene-C60 is a molecule with an interesting structure in which carbon atoms are spherically connected, and its use in cosmetic field has been associated to wrinkle prevention [187]. Radical Sponge is a fullerene developed to prevent skin damage caused by UV radiation, present in some cosmetic formulations, for example, the UNT Elixirin C60 Precious Eye Complex and Elixirin C60 Serum [188]. ...
... Fullerene derivatives and dendrimers are supramolecular structures with dimension of few nanometers and therefore can be considered as nanoparticles. Fullerenes have been investigated for their ability to absorb UV light and their radical scavenging properties [25, 57]. Dendrimers are highly branched structures, the peripheral groups of which can be used to attach several drug molecules, as well as targeting and solubilizing groups. ...
... In addition, certain nanoparticles possessing antioxidative properties have been proposed as components of anti-aging cosmetic products. In a clinical trial, a formulation of fullerene (C 60 ) dissolved in squalene has been tested for its anti-wrinkle efficacy [57] . Diverse cosmetic products taking advantage of the use of nanoparticles in galenical formulations to improve the barrier function of the skin are already in the market, e.g., Eczemel cream (DERMA- VIDUALS Ò USA) containing nanoparticles loaded with primrose oil and urea. ...
... [8][9][10][11][12][13][14] However, no drug candidate based on a fullerene scaffold has entered clinical trials, apart from dermatological studies to test the anti-wrinkle property of fullerene-C60 in humans. 15 One of the biggest challenges is to understand the nature of interactions between DFNs and proteins. Complex interactions between fullerenes and proteins can be categorized into three main subgroups: π-π stacking (between fullerene sp 2 carbons and aromatic residues of proteins); van der Waals (between the C 60 cage and protein surface); and hydrophobic (i.e., nonpolar solvation). ...
Teaser: Fullerene nanomaterials can interact with several proteins; thus, understanding of these interactions is crucial for designing engineered buckyballs with beneficial properties for further use in medicinal chemistry. Fullerenes have numerous properties that fill the gap between small molecules and nanomaterials. Several types of chemical reaction allow their surface to be ornamented with functional groups designed to change them into 'ideal' nanodelivery systems. Improved stability, and bioavailability are important, but chemical modifications can render them practically soluble in water. 'Buckyball' glycofullerene scaffolds can interact with many biological targets and inhibit several proteins essential for tumorigeneses. Herein, we focus on the inhibitory properties of fullerene nanomaterials against essential proteins in cancer nanotechnology, as well as the use of dedicated proteins to improve the bioavailability of these promising nanomaterials.
... Fullerene NPs even have been used in cream formulations for their brightening effects, 33 achieved by the removal of UV-induced free radicals and the inhibition of excessive melanin production. Clinical trials also showed the efficiency of C60 derivatives for the combined effects of skin wrinkle therapy, accelerated wound healing 34,35 and skin dressing membranes. 36,37 Formulating ...
Nanotechnology-based formulations have revolutionized the cosmetics industry. Nanoformulations can improve the behavior release of the ingredients and their skin penetration, two important factors in advanced cosmetics technology. Recently, fullerene nanoparticles and their derivatives have gained attention as one of the most developed types of cosmetic additive ingredients. Fullerene nanoparticles are useful in dermatological formulations because of their high antioxidant activities and reactive oxygen species (ROS) scavenging functions. This review summarizes recent trends in the development of fullerene-containing cosmetic skincare products.
https://www.cosmeticsandtoiletries.com/magazine/article/22144416
... Regarding fullerenes, the main obstacle is their poor solubility; however, this can be overcome either by using their derivatives or by encapsulating them into liposomes [38]. The most commonly used fullerenes in the cosmetics industry are fullerene C60 and fullerene C70, and although they are approved as antimicrobial and skin-conditioning agents, they are also applied in anti-ageing, whitening, and sun care products [39][40][41]. Very recently, on 6 July 2021, the European Commission requested a scientific opinion on fullerenes and their derivatives from the Scientific Committee for Consumer Safety. This was triggered from 19 requested notifications for new cosmetic products containing fullerenes. ...
Cosmetic and food products containing water are prone to contamination during the production, storage, and transit process, leading to product spoilage and degraded organoleptic characteristics. The efficient preservation of food and cosmetics is one of the most important issues the industry is facing today. The use of nanotechnology in food and cosmetics for preservation purposes offers the possibility to boost the activity of antimicrobial agents and/or promote their safer distribution into the end product upon incorporation into packaging or film constructions. In this review, current preservation strategies are discussed and the most recent studies in nanostructures used for preservation purposes are categorized and analyzed in a way that hopefully provides the most promising strategies for both the improvement of product safety and shelf-life extension. Packaging materials are also included since the container plays a major role in the preservation of such products. It is conclusively revealed that most of the applications refer to the nanocomposites as part of the packaging, mainly due to the various possibilities that nanoscience offers to this field. Apart from that, the route of exposure being either skin or the gastrointestinal system involves safety concerns, and since migration of nanoparticles (NPs) from their container can be measured, concerns can be minimized. Conclusion: Nanomaterial science has already made a significant contribution to food and cosmetics preservation, and rapid developments in the last years reinforce the belief that in the future much of the preservation strategies to be pursued by the two industries will be based on NPs and their nanocomposites.
... Fullerene-C60 is a molecule with an interesting structure in which carbon atoms are spherically connected, and its use in cosmetic field has been associated to wrinkle prevention [187]. Radical Sponge is a fullerene developed to prevent skin damage caused by UV radiation, present in some cosmetic formulations, for example, the UNT Elixirin C60 Precious Eye Complex and Elixirin C60 Serum [188]. ...
... The fullerenes are able to scavenge the free radicals and protect the cells from apoptosis. Because of such antioxidant nature of fullerenes, they are highly useful in anti-aging cosmetic products, for example, fullerene-C60 (Lipo-Fullerene) is used as a potential ingredient because of the anti-wrinkle property of fullerenes [91][92][93]. ...
The field of nanotechnology is being greatly explored by cosmetic industries in order to improve the efficacy of cosmetic products. The increased use of nanomaterials in the field of cosmetics can have two sides as health-related benefits and detrimental effects. This review mainly seeks the pros and cons of the use of nanomaterials in cosmetics along with some examples of nanomaterials that are widely used in cosmetic industries along with different types of nanotechnology-based cosmetic products. The benefits of nanomaterials in cosmetic formulations are huge. Moreover the study regarding the toxic effects on the health also equally matters. This review gives a brief outline of the advantages as well as disadvantages of nanotechnology in cosmetics.
... To the best of our knowledge there are as yet no clinical trials using such materials for neuroregeneration, although there are a couple that utilize some of the materials mentioned for other purposes. One clinical trial used fullerene-C60 (i.e., buckyballs) as a cosmetic ingredient with antioxidant ability, that was applied to the face for 8 weeks as part of an anti-wrinkle formulation and showed no severe side effects in the 23 person randomized control trial [346]. Another clinical trial utilizes graphene incorporated into latex condoms to study performance and safety [347]. ...
... Carbon nanomaterials (CNMs) take up a unique position in nanoscience and technology. Because of their excellent properties such as high chemical stability, mechanical strength, specific surface area, and electrical conductivity, CNMs have been applied in multiple areas (Choi et al. 2010;Eissa et al. 2017;Jariwala et al. 2013;Hou et al. 2016;Kato et al. 2010;Liu et al. 2009). The big amount of production and utilization of CNMs will inevitably give rise to the release of them into the environment, resulting in potential risks to human health and the ecological environment (Hou et al. 2017;Pérez et al. 2009;Selck et al. 2016;Wang et al. 2010). ...
While the application and discharge of carbon nanomaterials (CNMs) increased rapidly, the research on the environmental safety of CNMs is also increasing. The high dispersity and mobility of modified CNMs in environmental media may have impacts on the environmental behavior of heavy metals. This work mainly studied the effect of fullerol nanoparticles (C60(OH)n) on Cu²⁺ transport, sorption, and release in water-saturated porous media. The results showed that due to the strong adsorption capacity of C60(OH)n for Cu²⁺, the transport of Cu²⁺ could be facilitated. However, with the pre-existence of C60(OH)n in porous media, the transport of Cu²⁺ was also slightly enhanced. In addition, when loaded into the pre-contaminated porous medium, the C60(OH)n also enhanced the release of retained Cu²⁺, which implies a high environmental risk of C60(OH)n.
... (2,3) Fullerene (C60) allotrope has shown promise in cosmetic usage, dietary supplements and as an antitumor agent. These properties are primarily linked to its high antioxidant response and photodynamic cytotoxic effect on tumors (4)(5)(6)(7). Nevertheless, potential of Fullerene for nanomedicine development is not yet fully explored, partly due to dispersion problems of pristine Fullerene. ...
A bstract
We have developed Fullerene-C 60 nanoformulations containing discrete sized nanoparticles by dispersing concentration range of Fullerene. Small sized particles are cytotoxic while larger ones are cell proliferative. The cell proliferative property is used for tissue repair in cellular and animal wound models.
... Scientists try to improve the potential of carbon-based material in their wastewater filtration systems. According to broad application fields and as consequences the possibility of the releasing of these nanostructures in the ecosystem there is a huge demand to learn the influence of carbon-containing nanomaterials on food chain, plant and animal organisms [144][145][146][147][148][149][150][151]. ...
Nanomaterials include dispersing materials containing structural elements (grains, crystallites, blocks, clusters, etc.), due to their nano dimensions acquire qualitatively new functional and operational characteristics, offering several biomedical and technical advances over their bulk analogues. Taking into the consideration the fact that the impact of nanoparticles (NPs) to a living organism through the food chain is extremely important and have not been studied in detail yet, in this review we aimed to show the effect of different NPs towards terrestrial food chain, aquatic ecosystem, microorganisms and etc. Understanding and managing the potential risks associated with the use of nanoscale objects serves as a guide for developing new methods, tools, and concepts in order to determine how new engineering nanoparticles will interact with living organisms in the food chain and environmental systems. It is assumed that these methods will fundamentally differ and challenge the existing research and testing methodologies.
... Mainly studied due to their cytotoxicity and nonbiodegradable accumulation, a factor limiting their use in humans [7] Fullerenes Supermolecular structures are considered nanoparticles, they are investigated due to their capacity to absorb UV radiation and eliminate free radicals [8,9] ...
Nanotechnology is the manipulation of material with size
... Более того, было показано отсутствие токсичности фуллерена даже при системном введении (см., например, [91]). Не было выявлено каких-либо токсикологических проблем и в результате многочисленных исследований конкретных используемых в косметике форм фуллерена [92][93][94]. Кроме того, была установлена способность фуллерена проникать только в верхние слои кожи [95]. Причем этой способностью обладает не только сам фуллерен, но и фуллерен в виде комплекса с ПВП (С 60 /ПВП) [96]. ...
The review focuses on the possibilities and prospects of the use of fullerenes and their derivatives in cosmetics, the only industrial area where fullerenes have found practical application today. Based on the literary data and the results of their own experiments, the authors substantiate the safety of using fullerene for living organisms, as well as the usefulness of introducing fullerene as antioxidant in cosmetic compositions. Other useful properties of fullerene used in cosmetics and dermatology are discussed.
... Topical administration of oleuropein reduces UVB-induced erythema in human skin in vivo [9]. In addition, the application of a cream containing squalene is capable of mitigating fine wrinkles around the eyes [13]. In rodent models, the administration of extra-virgin olive oil rich in phenolic antioxidants increases the survival of aged rats and decreases DNA oxidative damage in circulating leukocytes and lipid peroxidation in plasma [14]. ...
Objective
Chronic stress‐induced oxidative damage and protease synthesis cause a loss of extracellular matrix components promoting human skin aging. The administration of antioxidant compounds, such as those observed in olive oil, may attenuate stress‐induced aging signs in human skin. Thus, the aim of this study was to investigate the effect of olive oil administration in ex vivo stressed human skin.
Methods
Explants of human skin were treated with high levels of epinephrine (as observed in stressed patients) and olive oil in medium for 13 days. Cultures treated with medium alone were used as controls.
Results
Olive oil reversed the high epinephrine level‐induced reduction in epidermis and dermis thickness and collagen fiber content in ex vivo human skin. The increase in the production of reactive oxygen species (ROS) and malondialdehyde levels (an index of lipid peroxidation) promoted by high levels of epinephrine were also attenuated by olive oil in ex vivo human skin. Moreover, olive oil was able to reverse the high epinephrine level‐induced increase in extracellular signal‐related kinase 1/2 (ERK 1/2) and c‐JUN (a major component of transcription factor AP‐1) phosphorylation and protein matrix metalloproteinase‐2 (MMP‐2) expression in ex vivo human skin.
Conclusion
Olive oil attenuates stress‐induced aging signs (thinner dermis and collagen fiber loss) in ex vivo human skin by reducing MMP‐2 expression, ROS production, and ERK 1/2 and c‐JUN phosphorylation.
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... Companies like Vitamin C60 BioResearch Corporation have developed CF-based products like LipoFullerene™ using squalane. Clinical findings in double blind studies advocate the antiwrinkle nature of LipoFullerene™ [93][94][95][96][97]. CF-based sponges have been reported to inhibit melanogenesis in human melanocytes and are proposed as skin whitening agents [98]. ...
Background:
C60-fullerenes (CFs) constitute a carbon-allotropic family with cage-like fused-ring structure, comprising of 20 hexagons and 12 pentagons. Since discovery in 1985, CFs attracted the scientists from various strata for unique properties like tensile strength, nanometeric size, symmetric nature, thermal and photo conductivity, chemical tailoring opportunities and drug loading capabilities. Surprisingly, CFs are also established to possess antiviral, neuroprotective, antiinflammatory, MRI contrast and antioxidant properties. Though extensively explored for chemical modifications and therapeutic benefits, CFs and derivatives also offer immense promises in drug delivery, especially to the cancerous cells.
Objective:
The present review is an attempt to highlight the promises of CFs in drug delivery, esp. of anticancer agents. The review also analyzes the safety concerns of CF-based drug delivery and attempts to discuss the promises and challenges in the light of preclinical and clinical data.
Methods:
The raw material (research/review articles) for the manuscript was collected from Pubmed, Google scholar and Scopus and the keywords used were fullerenes, nanotechnology, nanomedicine, functionalization, safety, drug delivery and biomedical applications.
Conclusion:
The drug release rate controlling behavior, higher drug loading, immuno-neutrality, substantial biocompatibility, capability to bypass mononuclear phagocytic system, long circulating nature and tissue extraction by virtue of enhanced permeability and retention effect are the major promises of these nanocarriers. On the other hand, the concerns like elimination from the biological system, anticipated tissue toxicity, stability of the final product, sterility issues and commercial viability pose challenges in proper utilization of CFs as ideal drug delivery carriers. However, a few commercial products based on CFs with human safety evidences provide a ray of hope.
... C 60 and its fulleropyrrolidine derivatives, incorporated in multilamellar liposomes, exhibit high skin absorption and excellent antioxidant activity without any significant biological toxicity. [26][27][28] Currently, there are no fullerene based commercial products that have made a significant impact, but there is a niche market for C 60 as an antioxidant in cosmetics. It was used as a C 60 /PVP complex 'Radical Sponge' 29 and squalane-dissolved fullerene C 60 'LipoFullerene'. ...
In 1996 Sir Harold W. Kroto, Robert F. Curl and Richard E. Smalley were honored with the Nobel Prize in Chemistry for the discovery of fullerenes. The advent of these new forms of carbon heralded a race to understand the physical and chemical properties. C60 is virtually insoluble in polar solvents but is partially soluble in benzene, toluene, and carbon disulfide. This made the processing of fullerenes for new applications fairly problematic. However, the physical and chemical properties of these cage structures may be tailored for a wide range of applications. Some of the difficulties in processing have been overcome by using novel fullerene derivatives. The functionalization of the fullerene core with different chemical moieties provided a vector toward potential applications in drug delivery, optoelectronics, electrochemistry and organic photovoltaics. In this review, we will take a closer look at the features of some of the fullerene derivatives that have reinvigorated the field of fullerene research. Water-soluble polyhydroxylated fullerenes such as fullerenol have demonstrated the potential for good electron transfer and optical transmission, while hydrophobic fullerene derivatives have shown promising avenues for catalytic applications. 2015 marked the 30th anniversary of the discovery of fullerenes, with celebrations around the world including an event by the Royal Society of Chemistry, bringing together many of Sir Harold Kroto's former students. The event also coincided with the recent discovery of C60+ in space after a complex twenty-year search. It is with sadness that we, Harry's Research Group at Florida State University, and his international collaborators, reflect on the passing of Sir Harold Kroto. His dedication to science and commitment to science communication through the VEGA Science Trust and the Global Educational Outreach for Science Engineering and Technology (GEOSET) initiative help to raise awareness of the challenges for science in the modern world. We will continue to inspire young students through outreach activities he initiated.
... Kato et al 87 assessed the anti-wrinkle effect of fullerene and found that LipoFullerene in squalane (LF-SQ) can prevent wrinkles caused by 2,4-nonadienal in 3D-human skin tissue model. They also ran a double-blind randomized controlled trial in which they asked 23 healthy women to use LF-SQ twice a day for 8 weeks 88 and saw that treated areas had less wrinkles; the observed difference was found to be statistically significant. No side effect was seen in their study. ...
Nanoparticles are equipped with exceptional properties which make them well suitable for diverse and novel applications. Fullerene is one of the nanomaterials that has valuable applications in the field of biomedicine. It possesses exceptional antioxidant capacity which has made it a promising core ingredient in many dermatological and skin care products. However, fullerene has the potentials to display a range of activities resulting in cell death or dysfunction. This review outlines the achievements made so far by reporting studies that have focused on incorporating fullerene in skin care products and cosmetics and assessed their beneficial effects. We have also documented reports that have assessed toxicity of this novel carbon allotrope toward skin cells and discussed its possible dermal reactions. Aside from pointing out the recent developments, areas that can benefit from further researches are identified.
... Other areas where carbon nanotubes can be used include various electronic applications [9,45]. Fullerenes and their derivatives can be used in medicine [46], including drug and gene delivery [47] or in cosmetics [48][49][50]. Graphene has numerous applications as well: it can be used in electronics, various biochemical sensors, in solar cells and others summarized in a recently published review by Choi et al. [51]. Beside the examples listed above, carbon-based nanomaterials also have numerous potential applications in the environmental and agricultural sectors, summarized in Fig. 3. ...
During the relatively short time since the discovery of fullerenes in 1985, carbon nanotubes in 1991, and graphene in 2004, the unique properties of carbon-based nanomaterials have attracted great interest, which has promoted the development of methods for large-scale industrial production. The continuously increasing commercial use of engineered carbon-based nanomaterials includes technical, medical, environmental and agricultural applications. Regardless of the application field, this is also associated with an increasing trend of intentional or unintended release of carbon nanomaterials into the environment, where the effect on living organisms is still difficult to predict. This review describes the different types of carbon-based nanomaterials, major production techniques and important trends for agricultural and environmental applications. The current status of research regarding the impact of carbon nanomaterials on plant growth and development is summarized, also addressing the currently most relevant knowledge gaps.Graphical abstractThe study reviews recent research activities exploring synthesis of carbon nanomaterials, their potential applications and impacts on plant development
Nanotechnology is a relatively new field of engineering that has led to the development of nanomedicine. Many of the benefits and risks surrounding nanotechnology concern the skin, and research over the last few decades has led to a better understanding of the potential role for nanotechnology in dermatology. As this field is rapidly evolving, practitioners must stay up to date on current research. This chapter will discuss the current uses and future direction of nanomaterials in cosmetic, diagnostic, and therapeutic dermatology.
Nanotechnology exhibits the advancement in the field of invention, by improving the potency of the formulation through the delivery of inventive solutions. To resolve several limita-tions related to conventional formulations, nanotechnology applications are increasing in the cosmetics and dermatological area. Cosmetic and dermatological preparations are considered a thriving branch of the body care arena and their usage has increased dramatically through the past years. Scientists are designing innovative delivery mechanisms and emerging innovations that are presently being utilized in the development of cosmetics. Inventive nanocarriers such as nio-somes, liposomes, microemulsions, nanoemulsions, solid-lipid nanoparticles, nanospheres, and nanostructured (lipid) carriers have substituted the use of traditional drug delivery. These innova-tive nanocarriers have the convenience of better skin permeation, sustained and controlled drug delivery, precise location, higher stability, and greater incorporated capability. Since the usage of cosmetics has increased, the usual delivery system has been substituted by modern delivery ap-proaches. The introduction of newer advancements and novel drug delivery systems make cos-metics and cosmeceuticals more popular with increased market share. This review article on nan-otechnology employed in cosmetics and dermatology emphasizes the numerous innovative nanocarriers designed for cosmetic and dermatologic drug delivery, their negative and positive aspects, and their toxicity.
The review systematizes data on the wide possibilities of practical application of carbon nanostructures. Much attention is paid to the use of carbon nanomaterials in medicine for the visualization of tumors during surgical interventions, in the creation of cosmetics, as well as in agriculture in the creation of fertilizers. Additionally, we demonstrate trends in research in the field of carbon nanomaterials with a view to elaborating targeted drug delivery systems. We also show the creation of nanosized medicinal substances and diagnostic systems, and the production of new biomaterials. A separate section is devoted to the difficulties in studying carbon nanomaterials. The review is intended for a wide range of readers, as well as for experts in the field of nanotechnology and nanomedicine.
Background
Nanoparticle formulations development for anti-aging treatment is increasing due to their multifunctional properties. These nanotechnological strategies can target cellular/molecular pathways of the skin affected by the aging process. However, a review of these strategies is required to discuss their efficacy/safety and establish the needs for further research.
Objective
Innovative nanotechnological advances for skin anti-aging/rejuvenation are summarized and discussed in this work.
Method
The information in this review was extracted from recent and relevant studies using nanotechnology for anti-aging treatment from scientific databases.
Results and discussion
Results show an enhanced skin anti-aging effect of actives-loaded nanoparticles of next generation (nanostructured lipid carriers, fullerenes, transfersomes, protransfersomes, niosomes, ethosomes, transethosomes, glycerosomes, phytosomes) compared with nanocarriers of first generation or conventional formulations. Anti-aging active ingredients such as, flavonoids (rutin, hesperidin, quercetagetine, quercetin, epigallocatechin-3-gallate, myricetin, silibinin, curcuminoids, isoflavones); vitamins (E, D3, CoQ10); acids (hyaluronic, ascorbic, rosmarinic, gallic); extracts (Citrus sinensis, Tagetes erecta L., Achillea millefolium L., Citrus aurantium L., Glycyrrhiza glabra L., Aloe vera, propolis earned by Apis mellifera); and other compounds (adenosine, beta-glucan, heptapetide DEETGEF, resveratrol, cycloastragenol, melatonin, botulinum toxin, grapeseed oil), have been successfully entrapped into nanoparticles for skin rejuvenation. This encapsulation has improved their solubility, bioavailability, stability, permeability, and effectivity for skin anti-aging, providing a controlled drug release with minimized side effects.
Conclusion
Recent studies show a trend of anti-aging herbal active ingredients-loaded nanoparticles, enhancing the moisturizing, antioxidant, regenerating and photoprotective activity of the skin. Suitable safety/shelf-life stability of these novel formulations is key to a successful translation to the clinic/industry.
Most alternative treatments are to be taken by mouth; less often they must be applied externally as creams. These modalities include, for instance, dietary supplements, homeopathic remedies, or herbal medicines. In this chapter, I discuss prominent examples from these categories. As there are many more, I focus on those that are best-known.
Nanocosmetics are personal care products containing nanocarriers or nanoparticles. These carriers increase formulation efficacy and promote controlled release of active ingredients. Cosmeceuticals are regarded as the fastest growing segment of the personal care industry, and the use has risen drastically over the years. For successful product development and production of nanocosmeceuticals, the interplay between material properties, formulation, process equipment, and process parameters must carefully be understood. Formulation with additives is crucial for the process performance as well as for product stability. Equipment should be operated in optimal parameter settings to combine the advantages of low energy consumption, high productivity, high product quality, and low product contamination. This chapter describes nanocarrier-based cosmeceuticals production, characterization, patent indeed on production method, and use of nanocosmeceuticals and also regulatory issues related to production of nanocosmeceuticals.
One of the essential organs and protective barricades, the skin, needs to be taken care of early. Skin is affected by several intrinsic and extrinsic factors, and despite their morphological and pathological differences, they have many molecular similarities. As of today, various mechanisms and theories have been recommended for aging, such as cellular anility, reduced proliferative tendency, reduction in length of telomere, mutations in DNA, theory of free radical generation, and many others. In today's society, skin health is often considered an important indicator of health, which has led to an increased demand for anti-aging products. However, numerous conventional cosmetics and phytocompounds (curcumin, Vitamin E, resveratrol) utilized in anti-aging products have inimical physical and chemical attributes, including insufficient chemical stability and inadequate skin penetration bound their effectuality after topical administration. So recently, new novel nanotechnological approaches for preventing skin aging, such as liposomes, niosomes, solid lipid nanoparticles, transferosomes, ethosomes, nanostructured lipid carriers, and carbon nanotubes, are being used. Hence, the field of cosmeceutical nanomaterials is rapidly evolving, and we can look forward to seeing a variety of innovative nanotechnology-based cosmetic products be a game-changer for this multi-million anti-aging cosmetic industry.
Nanotechnology is the future perspective technology, presenting and contributing to all inventive resourceful areas. It has emerged as a flexible platform for providing solutions to the sustainability challenges of the global community. Nanomaterials, especially those composed of carbon atoms that are termed carbon-based materials or carbon nanomaterials, have been garnering immense attention from the scientific community during the last three decades due to their significant physicochemical properties. These carbon nanomaterials that exists in zero, one, two, and three dimensions such as fullerenes, carbon nanotubes, graphene, carbon quantum dots, carbon nanohorns, nanodiamonds, carbon nanofibers, carbon nanosheets, carbon nanowires, and carbon black have shown innate characteristics such as high surface area, high mechanical stability, adaptability, and functionality that can be easily utilized in the development of advanced technology for sensing applications. These carbon nanomaterial-based sensors have been used in various fields for the detection of different analytes. Different types of sensors like chemical sensors, electrochemical sensors, biosensors, biochemical sensors, image sensors, and monitoring sensors have been reported in the literature. This chapter deals with prospects and possibilities of the development and applications of carbon nanomaterial-based sensors for a sustainable future.
The cosmetic industry is dynamic and ever-evolving. Especially with the introduction and incorporation of nanotechnology-based approaches into cosmetics for evincing novel formulations that confers aesthetic as well as therapeutic benefits. Nanocosmetics acts via numerous delivery mechanisms which involves lipid nanocarrier systems, polymeric or metallic nanoparticles, nanocapsules, dendrimers, nanosponges,etc. Each of these, have particular characteristic properties, which facilitates increased drug loading, enhanced absorption, better cosmetic efficacy, and many more. This article discusses the different classes of nanotechnology-based cosmetics and the nanomaterials used for their formulation, followed by outlining the categories of nanocosmetics and the scope of their utility pertaining to skin, hair, nail, lip, and/or dental care and protection thereof. This review also highlights and discusses about the key drivers of the cosmetic industry and the impending need of corroborating a healthy regulatory framework, refocusing attention towards consumer needs and trends, inculcating sustainable techniques and tenets of green ecological principles, and lastly making strides in nano-technological advancements which will further propel the growth of the cosmetic industry.
Carbon-based conductive and electroactive materials (e.g., derivatives of graphene, fullerenes, polypyrrole, polythiophene, polyaniline) have been studied since the 1970s for use in a broad range of applications. These materials have electrical properties comparable to those of commonly used metals, while providing other benefits such as flexibility in processing and modification with biologics (e.g., cells, biomolecules), to yield electroactive materials with biomimetic mechanical and chemical properties. In this review, we focus on the uses of these electroconductive materials in the context of the central and peripheral nervous system, specifically recent studies in the peripheral nerve, spinal cord, brain, eye, and ear. We also highlight in vivo studies and clinical trials, as well as a snapshot of emerging classes of electroconductive materials (e.g., biodegradable materials). We believe such specialized electrically conductive biomaterials will clinically impact the field of tissue regeneration in the foreseeable future.
Statement of Significance
This review addresses the use of conductive and electroactive materials for neural tissue regeneration, which is of significant interest to a broad readership, and of particular relevance to the growing community of scientists, engineers and clinicians in academia and industry who develop novel medical devices for tissue engineering and regenerative medicine. The review covers the materials that may be employed (primarily focusing on derivatives of fullerenes, graphene and conjugated polymers) and techniques used to analyze materials composed thereof, followed by sections on the application of these materials to nervous tissues (i.e., peripheral nerve, spinal cord, brain, optical, and auditory tissues) throughout the body.
Nanocarrier technology has been effectively applied to the development of drug delivery systems to overcome the limitations of traditional preparation. Its application has been extended to various pharmaceutical fields from injection preparation to oral preparation and external preparation, and now it has appeared in the field of cosmetics for beauty applications. The widespread influence of nanocarrier in the cosmetics industry is due to the fact that nanocarrier can effectively promote the percutaneous penetration and significantly increase skin retention of active components in functional cosmetics. Meanwhile, nanocarrier can effectively improve the water dispersion of insoluble active cosmetic ingredients, enhance the stability of efficacy components and achieve the codelivery of diverse cosmetics active ingredients. In this review, we summarized the current progress of nanocarrier technology in the functional cosmetics, including the types and the routes of dermal/transdermal drug delivery nanocarriers used in the functional cosmetics, the mechanism of nanocarriers promoting the percutaneous penetration of active cosmetic ingredients, the application and efficacy evaluation of different active cosmetic ingredients in nanocarriers and discussing the potential risks to human. This will provide a useful reference for the further development of nanocarriers in the field of functional cosmetics.
Biomass-derived nanocarbons (BNCs) have attracted significant research interests due to their promising economic and environmental benefits. Following their extensive uses in physical and chemical research domains, BNCs are now growing in biological applications. However, their practical biological applications are still in infancy, requiring critical evaluations and strategic directions, which are provided in this review. The carbonization of biomass sources and major types of BNCs were introduced, encompassing carbon nanodots, nanofibres, nanotubes, and graphenes. Next, essential biological uses of BNCs: antibacterial/antibiofilm materials (nanofibres and nanodots) and bioimaging agents (predominantly nanodots) were summarized. Further, the future potential of BNCs, for designing wound dressing/healing materials, water and air disinfection platforms, and microbial electrochemical systems, were discussed. We reach the conclusion that a crucial challenge is the structural controls of BNCs. Further, a key knowledge gap for realizing practical biological applications is the lack of systematic comparisons of BNCs with nanocarbons of synthetic origins in the current literature. Although we did not attempt to perform an exhaustive literature survey, the evaluation of existing results indicates that BNCs are promising as easily accessible materials for various biomedically and environmentally relevant applications.
The dynamics of the fullerene molecule (C60) in the different aromatic solvents has been probed using all‐atom molecular dynamics simulation. For this study, the four aromatic solvents, (1) 1‐chloronaphthalene, (2) 1‐methylnaphthalene, (3) 1,2,4‐trimethylbenzene, and (4) chlorobenzene, have been used. The 1‐chloronaphthalene is important due to the high solubility (51 g/L) of the fullerene in it. The rest of the three solvents have the decreasing order of solubility. In this work, the nature of diffusion of the fullerene and the solvents are studied. It is found that if the concentration of the fullerene molecule is same in different solvents, then the hydrodynamic radius of the fullerene molecules obeys a linear relation with solubility. Hydrodynamic radius of fullerene is found to increase with a decrease in solubility. The radial distribution function of fullerene and solvents is used to calculate their relative orientation. The free energy of solvation of fullerene in these four solvents is also calculated.
Introduction
The effect of fullerene nanoemulsion on skin wrinkle repair in an animal model was evaluated using ultrasonic images processing.
Methods
Wrinkles were created in C57BL6 mice during 35 days of UVB radiation. Then, to investigate the therapeutic effect of fullerene nanoemulsions, mice were divided into three groups of control, UVB radiation, and treatment with fullerene nanoemulsion. Stable fullerene nanoemulsions were prepared using shear equalization. The therapeutic effect of fullerene nanoemulsion was investigated by extracting the skin thickness and mechanical parameters. Histology studies were performed to confirm the reliability of the treatment.
Results
A significant decrease was observed in the thickness of the epidermis and dermis layers (43% and 36%), Young modulus (27%), and the shear modulus (20%) of the skin on day 28 of the fullerene nanoemulsion treatment. Skin stiffness obtained by tensiometry on day 28 of the treatment showed a 48% reduction in the treatment group compared with the control group. Histological results confirmed the effect of fullerene nanoemulsions on wrinkle repair.
Conclusion
The healing effect of fullerene nanoemulsion in wrinkle repair was confirmed. To study the skin repair, parameters including Young modulus, the shear modulus, and skin layer thickness can be calculated using ultrasonic images processing.
In the last decade, graphene‐based nanomaterials and carbon dots have joined the family of carbon materials mainly composed of graphite, diamond, fullerene, and carbon nanotubes. Carbon nanomaterials have been widely exploited in various fields from electronics and materials science to nanomedicine. The studies on their effect on the immune system have revealed that they possess intrinsic anti‐inflammatory properties, reducing the production of proinflammatory cytokines and modulating immune cell maturation. In addition, their large specific surface area associated with high biocompatibility allows their use as carriers for the delivery of anti‐inflammatory agents. They can also contribute to the diagnosis of inflammatory diseases as biosensors for low‐limit detection and quantification of inflammation‐related biomarkers in body fluids and tissues allowing to monitor the concentration of drugs in urine and guide personalized drug usage. Finally, they are used as adsorbents for blood plasma purification in the clinical treatment of sepsis through efficient removal of certain cytokines. This review focuses on the intrinsic anti‐inflammatory properties of carbon nanomaterials. An overview is provided on their use as carriers of anti‐inflammatory drugs, as biosensors, and for blood purification in the context of inflammatory diseases. The potential of carbon nanomaterials for clinical translation is also critically discussed.
The kinetics of the Bingel reaction with halogenmethyl ketones and C60 fullerene has been studied in streaming mode by sampling the reaction mixture at different time intervals and separating the components using HPLC. A quantum-chemical simulation of this cyclopropanation process has been carried out with the DFT method. The activation parameters of the cycloaddition process were determined theoretically and experimentally and correlated with each other. It has been revealed that the use of chloromethyl ketone as the cyclopropanation agent is preferable to its brominated analogue, and a two-fold excess of the substrate with respect to fullerene is the best option for the selective synthesis of mono-adducts.
Background
Fullerene water complex establishes the optimal order and function of biomolecules in natural, biophysical way by transducing the signal through water hydrogen bonds to biomolecules.
Objectives
This paper considers the effects of the patented hyper‐harmonized‐hydroxylated fullerene water complex (3HFWC) on biophysical properties of the skin collagen molecules.
Method
Optomagnetic imaging spectroscopy (OMIS) has been used for the analysis of the biophysical skin properties (diamagnetic/paramagnetic) after applying three groups of different cosmetic products. Tested cosmetic products were prepared by replacing the active ingredients with 3HFWC or with water in four commercial products. The original commercial creams and their vehiculums with water added served as control groups. Data were statistically analyzed using paired t test in R software.
Results
t Test gave statistically significant results for all of the products with 3HFWC, while within the control group, only body lotion and hand cream did show statistically significant results (P < 0.05). Significant improvements in abundance and quality of collagen in the dermis were achieved with body lotion with 3HFWC (p⁺/p⁻ranged from 0.82 to 0.97). While body lotion vehiculum made collagen‐water interaction more stable (p⁺/p⁻ranged from 0.3 to 0.55), hand cream with 3HFWC made it more dynamic (p⁺/p⁻ranged from 0.63 to 0.49). Body lotion vehiculum improved the compactness of the dermis (p⁺/p⁻ranged from 0.2 to 1.03), as well as commercial hand cream (p⁺/p⁻ ranged from 0.28 to 0.85).
Conclusion
Compared to the control groups, cosmetic products with 3HFWC demonstrated positive effects on the biophysical properties of the skin. Increased paramagnetic properties are linked to more unpaired electrons, their faster movement, and, finally, better signal transduction. Thus, products with 3HFWC could enable faster regeneration of collagen and prompt skin reaction to the negative environmental influences.
The aim of this study was to investigate whether oral administration of olive oil could attenuate chronic stress-induced signs of aging in mouse skin. The mice were subjected to daily rotational stress and treated with olive oil until the time of euthanasia (28 days). Murine dermal fibroblast cultures were exposed to increased epinephrine levels plus olive oil. Olive oil reduced catecholamine synthesis in the stressed mice. Moreover, olive oil inhibited stress-mediated increases in reactive oxygen species production, lipid peroxidation and protein carbonylation in mouse skin. Olive oil also inhibited stress-induced increases in matrix metalloproteinase-8 protein expression and collagen deposition in mouse skin. Additionally, olive oil reduced nuclear factor kappa B protein expression in the skin of stressed mice. In cultured dermal fibroblasts, olive oil abolished the increase in reactive oxygen species production and nuclear translocation of activated nuclear factor kappa B induced by high epinephrine levels. In conclusion, olive oil may attenuate stress-induced signs of aging in mouse skin.
The kinetics of nucleophilic fullerene cyclopropanation by halomethyl ketones with a diterpene fragment has been studied by the Bingel method, and the influence of the biologically active cyclopropanating agent on the process has been estimated. It has been revealed that favorable conditions for carrying out the reaction result in maximum monofunctionalized methanofullerenes formation with the maximum yield.
This chapter discusses the nature of nanoparticles with reference to skin and skin diseases; the potential of absorption of nanoparticles through skin; the nanoparticles in prevention, diagnosis and therapy; some regulatory issues, and; the public perception of nanoparticles in topical formulations. Nanomedicine, a subdivision of nanotechnology, opened up entirely new opportunities for highly specific interventions in prevention, diagnosis, and therapy. Typical rigid nanoparticles consist of metals such as gold or silver, metal oxides including titanium, zinc, or iron oxides, and ceramics such as silica. Solid lipid nanoparticles and nanostructured lipid carriers were developed to form more stable systems. The stability of the nanoparticles in the vehicle is a primary goal of any formulation development and a prerequisite of applied clinical research and subsequent commercialization. For clinical use, gold nanoparticles are being studied as carriers both for the delivery of drugs, imaging molecules, and genes and for the development of cancer therapy products.
To identify compounds that suppress UV irradiation-induced oxidative stress in the skin, various types of antioxidants have been studied. Polyvinylpyrrolidone-entrapped fullerene (C60/PVP) is known as a powerful antioxidant that exerts a cytoprotective effect against UV irradiation-induced cell injury in human skin cells and skin models. However, the effects of the alternate attractive C60/PVP feature, persistent antioxidant ability, on cytoprotection have rarely been ascertained. In this study we therefore investigated the efficacies of C60/PVP using an intermittently repeated UVA irradiation model wherein human keratinocytes were repeatedly exposed to UVA five times every 1h and compared the cytoprotective effects with those provided by ascorbic acid-2-O-phosphate-disodium salt (APS) and α-tocopherol (α-Toc). Our results demonstrated that C60/PVP yielded prominent cytoprotective effects against intermittently repeated UVA irradiation-induced injuries in a dose-dependent manner and suppressed intracellular superoxide anion radical (O2(-)) generation both during and after the repeated UVA irradiation. Additionally, C60/PVP also repressed the intermittent UVA irradiation-induced apoptosis via suppression of chromatin condensation and caspase-3/7 activation. Furthermore, the observed cytoprotective effects were superior to the effects of the typical antioxidants APS and α-Toc. These data suggest that C60/PVP might function as a potent cosmetic antioxidant against the effects of repeated and prolonged UVA irradiation through its persistent antioxidative property.
The recent progresses in tissue engineering and nanomaterial-based thera-peutics/theranostics have led to the ever increasing utilization of 3D in vitro experimental models as the bona fide culture systems to evaluate the therapeutic/theranostic effects of nanomedicine. Compared to the use of conventional 2D culture platforms, 3D biomimetic cultures offer unmatched advantages as relevant physiological and pathological elements can be incor-porated to allow better characterization of the engineered bio-nanomaterials in the targeted tissue-specific microenvironment. In this Feature Article, the current state-of-the-art 3D in vitro models that have been developed for the evaluation of biosafety and efficacy of nano- therapeutics/theranostics targeting the colon, blood–brain barrier (BBB), lungs, skin tumor models to bridge the nanomedicine bench to pre-clinical ravine are reviewed. Further-more, the critical physicochemical parameters of the bio-nanomaterials that govern its transport and biodistribution in a complex 3D microenvironment will be highlighted. The major challenges and future prospects of evaluating nanomedicine in the third dimension will also be discussed.
A selective photoluminescent method based on Carbon Dots (CDs) functionalize with carboxymethyl-β-cyclodextrin for the direct determination of water-soluble C60 fullerene has been developed. CDs were synthesized using the top-down methodology from multiwall carbon nanotubes (MWCNTs) and further functionalized with N-Boc-ethylenediamine to confer them ending monoprotected amine groups onto their surface. Once amine-functionalized CDs were obtained after deprotection, amidation reaction with carboxymethyl-β-cyclodextrin cavitand was achieved and the obtained fluorescent β-cyclodextrin functionalized Carbon Dots (cd-CDs) were investigated for the inclusion complexation of water-soluble C60. Quenching of their fluorescence was observed owing to the non-covalent self-assembly of cd-CDs and C60 making possible their quantification. A method to determine water-soluble C60 is then proposed with detection and quantification limits of 0.525 and 1.751 µg•mL-1, respectively. The method was validated determining soluble C60 fullerene in spiked river water. One added value of the paper is the facet that it can adscribed to the “Third Way of Analytical Nanoscience and Nanotechnology” (ANN).
We dissolved fullerene-C60 in squalane (LipoFullerene; LF-SQ, C60-eq.: 500 ppm) and examined its defensive effects against 2,4-nonadienal (NDA)-induced cell injury in HaCaT keratinocytes and wrinkle formation in three dimensional (3D)-human skin tissue model. NDA is an analog of 4-hydroxynonenal, one of major causes for human body odor indicative of aging and a lipophilic cell injury factor. Cell viability (% of the control) decreased to 31.6% on treatment with NDA (40 microM), but it increased to 66.0-97.5% when LF-SQ of 1-4% (C60-eq.: 5-20 ppm) was administered for 5 hr before NDA addition. The defensive effect by LF-SQ was superior to that of "squalane" alone at the same doses. NDA-induced DNA-fragmentation in HaCaT cells was suppressed by LF-SQ administered for 5 hr before NDA treatment, and LF-SQ protected HaCaT cells against apoptosis-like cell death. LF-SQ did not appreciably defend against hydrogen peroxide, though LF-SQ effectively defended against tert-butylhydroperoxide, a type of the intermediate hydrophilicity-lipophilicity degree out of other reactive oxygen species. The scanning electron microscopy demonstrated that NDA caused wrinkles and abnormal scales on keratinocytes of 3D-human skin tissue model, and structural homogeneity of the interstratum was broken, any of which were, however, markedly suppressed with LF-SQ. Squalane alone exhibited defensive effect against the skin tissue injury to some extent, but which was inferior to LF-SQ. LF-SQ might effectively capture and scavenge lipid radicals generated inside the cell membrane, because squalane acts as a lipophilic carrier of C60. C60 dissolved in squalane can be expected to serve as a cosmeceutical ingredient for anti-wrinkle formation.
One of the outward signs of the aging process of human skin is the increased appearance of wrinkles on its surface. Clinical studies show that the increased frequency of wrinkles with age may be attributed to changes in the composition of the various layers of skin, leading to a change in mechanical properties. A parameter study was performed on a previously proposed multi-layer finite element model of skin. A region of skin was subject to an in-plane compression, resulting in wrinkling. A number of physical properties of the skin model were changed and the effects these changes had on the size of the subsequent wrinkles were measured. Reducing the moisture content of the stratum corneum by 11% produces wrinkles 25-85% larger. Increasing the dermal collagen fibre density by 67%, results in wrinkles, which are 25-50% larger. A reduction and change in the pre-stress distribution in the skin model, which represents the natural tension and relaxed skin tension lines in real skin, also influences the wrinkle height in a similar manner to real aging skin. Typically, there can be up to a 100% increase in the height of wrinkles as skin ages. This model would be of benefit in the development of cosmetic moisturisers and plastic-surgery techniques to reduce the appearance of aging.
Microemulsification of triglyceride-based oil is challenging due to the formation of undesirable phases such as macroemulsions, liquid crystals, or sponge phases. This research evaluates the formation of artificial sebum microemulsions using linker molecules, with the addition of co-oil to help enhance sebum solubilization. The microemulsion consists of a lipophilic linker (sorbitan monooleate), a hydrophilic linker (hexylglucocide), a main surfactant (sodium dioctyl sulfosuccinate), a co-oil, and artificial sebum. The effect of adding co-oil to the phase behavior and the microstructure of the resulting microemulsion is described. The effect of several types of co-oil is also studied; the co-oils evaluated here are squalene, squalane, isopropyl myristate, and ethyl laurate. The effect of salinity on the microemulsion phase behavior is also presented. Fish diagrams are obtained by plotting total surfactant/linker concentration as a function of sebum fraction in the oil mixture (co-oil + sebum). Different microemulsion types (Winsor Types I, II, III, and IV) are formed, depending on the total surfactant/linker concentration and the fraction of co-oil in the oil mixture. Winsor Type IV (single-phase) microemulsions are observed at high surfactant/linker concentrations. These single-phase, isotropic, and low-viscous fluids are particularly useful for cleansing and delivery of functional ingredients in skin care products. Salt addition shifts the fish diagram towards more hydrophobic oil systems and higher surfactant/linker concentrations.
Superoxide radical anion is a biologically important oxidant that has been linked to tissue injury and inflammation in several diseases. Here we carried out a structure-activity study on six different carboxyfullerene superoxide dismutase (SOD) mimetics with distinct electronic and biophysical characteristics. Neurotoxicity via N-methyl-D-aspartate receptors, which involves intracellular superoxide, was used as a model to evaluate structure-activity relationships between reactivity toward superoxide and neuronal rescue by these drugs. A significant correlation between neuroprotection by carboxyfullerenes and their ki toward superoxide radical was observed. Computer-assisted molecular modeling demonstrated that the reactivity toward superoxide is sensitive to changes in dipole moment, which are dictated not only by the number of carboxyl groups but also by their distribution on the fullerene ball. These results indicate that the SOD activity of these cell-permeable compounds predicts neuroprotection, and establishes a structure-activity relationship to aid in future studies on the biology of superoxide across disciplines.
The uppermost layer of our skin, the epidermis, is formed largely of keratinocytes which constitute the skin's major barrier function and the first line of defence against environmental physical, chemical and biological agents. The subsequent layer, the dermis, which is mainly formed by fibroblasts, has a more supportive function, containing large amounts of collagen, blood vessels and nerve endings and is less directly affected by external insults. Hence it is likely that keratinocytes and fibroblasts have evolved different strategies to cope with the dangers of the environment. Mouse models with various genetic backgrounds in genome care-taking systems, such as DNA repair processes, are well suited to study differences between these two cell types and their implications for cancer and aging. In this chapter we describe a simple procedure to establish long-term keratinocyte and fibroblast cultures from, respectively, the epidermis and dermis of normal or NER-deficient newborn mice. The importance of the external O(2) pressure during the establishment and maintenance of these matched cultures is discussed.
There has been a considerable increase in understanding how skin ages, along with significant progress toward the correction and prevention of the visible signs of aging. However, there are still many unknown factors regarding why we age - and why we all seem to age differently. An area of high interest is the biological or intrinsic processes that affect our appearance over time. This article describes a recent discovery of a membrane bound enzyme proven to be present in skin and increases its activity as biological age increases. The enzyme is located on the external surface of both fibroblast and keratinocytes, and generates free radicals. Therefore, as we age there appears to be a biological mechanism that further increases the production of free radicals. Additionally, there appears to be a relationship between activity of the enzyme and appearance. Data showed that subjects who look younger than their biological age had lower enzyme activity and conversely, subjects who looked older than their biological age had higher enzyme activity. Free radicals are believed to be a major contributing factor in the production of fine lines and wrinkles by destroying the collagen and elastin network keeping skin supple and firm.
As cosmetic technology advances, there is an increasing need to use new active ingredients in the development of cosmetic products. In the last few years application of fullerene C(60) and its derivates in cosmetics has been intensively tested. Fullerenes display a wide range of biological activities. Potent scavenging capacities against radical oxygen species (ROS) and excellent potential as biological antioxidants made fullerenes suitable active compounds in the preparation of skin rejuvenation cosmetic formulations. Currently published evidence on biological activities of fullerenes relevant for their cosmetic use and examples of published patents to illustrate application of fullerenes in cosmetic technology are presented. Future trends in the development of cosmetic formulations including fullerenes are discussed.
Fullerene-C60 (C60) is mainly applied in the aqueous phase by wrapping with water-soluble polymer or by water-solublizing chemical-modification, whereas C60 dissolved in oil is scarcely applied; still less explicable is its toxicity.We dissolved C60 in squalane at near-saturated or higher concentrations (220-500 ppm), named LipoFullerene (LF-SQ),and examined its biological safety. LF-SQ was administered at doses of 0.49-1000 microg/ml to fibroblast cells Balb/3T3, and showed that cell viability was almost equal to that of the control regardless of the UVA- or sham-irradiation, indicating no phototoxicity. Reverse mutation by LF-SQ was examined on four histidine-demanding strains of Salmonella typhimurium and a tryptophan-demanding strain of Escherichia coli. As for the dosages of LF-SQ (313-5000 microg/plate), the dose-dependency of the number of reverse mutation colonies of each strain did not show a marked difference when compared with the negative control, regardless of the metabolic activation, in contrast to twice or more differences for five positive controls(sodium azide, N-ethyl-N'-nitro-N-nitrosoguanidine, 2-nitrofluorene, 9-aminoacridine, and 2-aminoanthracene). In human skin biopsy built in a diffusion chamber, C60 permeated into the epidermis at 33.6 nmol/g tissue (24.2 ppm), on administration with LF-SQ containing 223 ppm of C60, but not detected in the dermis even after 24 hrs, as analysed by HPLC. It is presumed that LF-SQ can permeate into the epidermis via the corneum but can not penetrate the basement membrane,and so can not reach into the dermis, suggesting no necessity for considering a toxicity of C60 due to systemic circulation via dermal veins. Thus, C60 dissolved in squalane may not give any significant biological toxic effects such as photocytotoxicity,bacterial reverse mutagenicity, and permeability into the human skin.
Free radicals are chemical species characterized by an odd number of orbital electrons or by pairs of electrons of similar directional spin isolated singly in separate orbitals. Consequently most of these agents are highly reactive and usually exhibit an extremely short half-life, although due to steric and resonance effects some exceptions occur. Some radicals and their precursors, such as the diradical O2 which exists in the triplet state, represent a critical and essential element of normal metabolism of aerobic organisms where, under normal circumstances, controlled reduction of reactive oxygen species occurs via the cytochrome oxidase or cytochrome P-450 mixed function monooxygenase systems. In addition to reactive oxygen species, organisms may be subjected to a wide-range of other free radicals or their precursors, including those of both exogenous and endogenous origin. Elaborate defense mechanisms have evolved to avoid cellular damage from these highly reactive species. Enzymes, such as the superoxide dismutase, the glutathione peroxidase/reductase system, and catalase; interactions with conjugated diene systems such as those found in melanins, carotenoids, and tocopherols; and direct reduction by sulphydryl compounds, phenols, and purines represent but a few of these natural defense systems.
The lethal effects of linoleic acid and its hydroperoxide on human diploid fibroblasts were quite similar, and that of the reaction mixture from the autoxidation of the hydroperoxide was considerable. Some unsaturated aliphatic aldehydes, the secondary products of the hydroperoxide autoxidation, were identified and their toxicity toward the cells was examined. Among them, (E,E)-2,4-nonadienal, (E,E)-2,4-decadienal, and (E)-4-hydroxy-2-nonenal were the most toxic; e.g., in the presence of 25 microM nonadienal, decadienal, or hydroxynonenal, 75, 90, or almost 100% of the cells, respectively, underwent lysis within one day. Generally, alkenals were toxic and alkanals non-toxic. The toxicity was enhanced as the number of double bonds in each molecule was increased and also as the carbon chain was lengthened.
Free fatty acids (FFA), squalene, squalene hydroperoxide, and uric acid in the methanol extracts from human skin surface were measured. Levels of FFA and squalene were significantly lower in the older (83.7 +/- 9.4 years) than in the younger (22.2 +/- 3.9 years) group. FFA are mostly saturated, and linoleic acid is an exclusive polyunsaturated fatty acid. The composition of linoleic acid decreased in the older group by 40%, suggesting age-dependent loss of oxidatively vulnerable polyunsaturated fatty acid. Even monounsaturated acids such as palmitoleic and oleic acids decreased significantly in the older group. This could be interesting because 2-nonenal is the oxidation product of palmitoleic acid and has been identified as the major aged body odor component. Sunlight exposure for 1.5 h did not change levels of FFA and squalene, or FFA composition. However, squalene hydroperoxide increased by 60-fold, as reported previously, suggesting that hydroperoxide is produced by singlet oxygen. Uric acid increased by two-fold, which may be the adaptive response against photo-oxidative stress because uric acid is a good scavenger of singlet oxygen and oxygen radicals.
Chemically generated hydroxyl radicals were scavenged by PEG-modified fullerene, hydroxy-fullerene and isostearate-mixed fullerene as efficiently as ascorbic acid (Asc) or its 2-O-phosphorylated derivative (A2P) as shown by the DMPO-spin trap/ESR method. Enzymatically generated superoxide anion radicals were also scavenged by PEG-modified or PVP-entrapped fullerene similarly as done by Asc or A2P. Some reactive oxygen species (ROS) such as hydroperoxides and hydrogen peroxides were generated preferably in the nuclei of UVB-irradiated human skin keratinocytes HaCaT, and repressed by PVP- or gamma-cyclodextrin-fullerene. In contrast, the cytoplasm in the keratinocytes accumulated the ROS that were generated by the peroxylipid model compound t-BuOOH, and underwent the ROS repression by PVP-fullerene more markedly than by A2P. Thus several fullerene derivatives, especially PVP-fullerene, were shown to diminish the ROS amounts in terms of the molecular and cellular levels against either UVB or t-BuOOH, suggesting the expectation for development as rejuvenation cosmetics.
Eight liquid emollients (mineral oil, sunflower oil, squalane, decyl oleate, isopropyl myristate, octyldodecanol, dimethicone, and cyclomethicone) were characterized by instrumental and sensory methods and evaluated to determine the relationship between sensory and instrumental measures. Sensory analysis was carried out by a panel of 14 assessors, who evaluated the following attributes: difficulty of spreading, gloss, residue, stickiness, slipperiness, softness, and oiliness. The physicochemical properties measured were spreadability (at one-half minute and at one minute), viscosity, and superficial tension. Data collected were statistically analyzed by analysis of variance (ANOVA), principal component analysis (PCA), and linear partial least squares regression analysis (PLS). In consideration of their physicochemical characteristics, the studied emollients were sorted into three groups, in which the silicones distinctly separate from the rest. Sensory characteristics enabled the discrimination of four groups of emollients where, besides the two silicones, isopropyl myristate was also differentiated. PLS revealed that emollient sensory attributes could be well predicted by instrumental measurements.
Systemic and topical application of antioxidant substances for the medical treatment and prophylaxis of many diseases as well as additional protection of the skin against the destructive action of free radicals and other reactive species has become very popular during the past years. Stimulated by the positive results of a fruit and vegetable diet in supporting medical treatment and in cosmetics, artificial and extracted antioxidant substances have been broadly applied. Surprisingly, not only positive but also strong negative results have been obtained by different authors. According to study reports artificial and extracted antioxidant substances support different kinds of medical therapies, if they are applied in mixtures of different compounds at low concentration levels. In the case of the application of high concentration of some single compounds, side effects were often observed. Regarding skin treatment by systemically applied antioxidant substances for cosmetic purposes, positive cosmetic effects as well as no effects, but almost no side effects, apart from a number of allergic reactions, were reported. One reason for this seems to be the lower concentration of systemically applied antioxidant substances in comparison with a medical application. Topical application of antioxidant substances is closely related to cosmetic treatment for skin protection and anti-aging. Positive results were also obtained in this case. The present review is an attempt to classify and summarize the published literature concerning the efficiency of action of systemic and topical applications of antioxidant substances, such as carotenoids and vitamins, on human organism and especially on the skin. The available literature on this topic is very extensive and the results are often contradictory. Nevertheless, there are some clear tendencies concerning systemic and topical application of antioxidant substances in medicine and cosmetics, and we summarize them in the present paper.
Photochemically generated benzyl radicals react with C(60) producing radical and nonradical adducts Rn C(60) (R = C(6)H(5)CH(2)) with n = 1 to at least 15. The radical adducts with n = 3 and 5 are stable above 50 degrees C and have been identified by electron spin resonance (ESR) spectroscopy as the allylic R(3)C(60)(.) (3) and cyclopentadienyl R(5)C(60)(.) (5) radicals. The unpaired electrons are highly localized on the C(60) surface. The extraordinary stability of these radicals can be attributed to the steric protection of the surface radical sites by the surrounding benzyl substituents. Photochemically generated methyl radicals also add readily to C(60). Mass spectrometric analyses show the formation of (CH(3))nC(60) with n = 1 to at least 34.