Nanotechnology in cosmetics pros and cons

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.


Introduction
Nanotechnology has wide applications in various fields such as agriculture, food, paints, medicine, textiles. The cosmetic industry has extensive use of nanomaterials for various benefits. The extensive surge in the customers' demands has led to the development of formulations in cosmetics with better performance, retentions, attractive appearance, and more importantly safety [1,2]. The major benefits of the use of nanoparticles in cosmetics include everlasting stability, proper penetration of formulation at the site of application. The integration of nanoparticles in cosmetics is gaining demand because of their high surface-tovolume ratio which helps in better penetration through the skin [3][4][5][6][7]. The property of UV filters of nanoparticles has made the nanoparticles which can be used in the Sunscreens. In 1986, for the first time, Christian Dior launched the anti-aging cream named Capture TM in which liposomes were used [8]. Later on, various cosmetic industries started the use of nanoparticles in the formulations of cosmetics. The very wellknown cosmetic manufacturers; L'Oréal S.A. registered about seven patents for the use of nanoparticles in cosmetic preparations [9]. TiO 2 , ZnO, silica, carbon black nanoparticles are used in some of their cosmetic products as shown in figure 1 [10,11].
The concerns regarding the usage of nanoparticles in cosmetics have been raised by various organizations such as World Health Organization (WHO), government as well as non-government organizations. The guidance regarding the use of nanoparticles has been proposed by European Commission (EC) and Food and Drug Administration (FDA) by their own guidance for the utilization of nanoparticles in cosmetics. The European Union Observatory for Nanomaterials (EUON) has set forth the REACH registration compliant (REACH is a Registration, Evaluation, Authorization, and Restriction of Chemicals). The usage of nanoparticles should fall under the limits of REACH and the main aim of it is to provide information regarding the safe usage of nanoparticles. The review presents the benefits and the harmful effects of nanoparticles in cosmetics along with a brief insight into the type of nanoparticles majorly used in the cosmetic industry [5,[12][13][14]. Firstly the review gives a brief outline of the types of nanomaterials used in cosmetic formulations along with their potential benefits followed by different types of nanotechnologybased cosmetics. Later the second section highlights the pros of nanomaterials in cosmetics. The latter part deals with the different facets of the effects of nanomaterials on the health and environment. Finally, different views are expressed along with few suggestions in order to reduce the adverse impacts of nanomaterials, which can be useful for further research in the above-stated subject.

Nanotechnology in cosmetics 2.1. Nanoparticles used in the cosmetic industry
The cosmetic industry is attaining the benefits of nanotechnology by developing nanoparticles for the enhanced performance and bioavailability of active components in cosmetics, sunscreens, anti-aging creams, moisturizers, and perfumes [15]. There are various nano-delivering systems used in cosmetic preparations to enclose vital elements. This is beneficial for the efficient delivery of active components via skin. The nano-based products are helpful in the efficient absorption and penetration through the skin. The active ingredients are adsorbed on the surface of nanoparticles which act as a vehicle for the delivery. The cosmetics may contain nanoparticles of different morphologies and chemical compositions to harness the advantages of shape and size-dependent activities of nanoparticles to exaggerate the activities of cosmetic products. The cosmetics are formulated by using different types of metal and metal oxide nanoparticles such as silver nanoparticles (AgNPs), gold nanoparticles (AuNPs) and titanium dioxide nanoparticles (TiO 2 NPs), zinc oxide nanoparticles, (ZnO NPs), iron oxide nanoparticles, (Fe 2 O 3 NPs) and carbon-based NPs [16][17][18]. The nanoparticles such as titanium dioxide (TiO 2 ), zinc oxide (ZnO) are substantially used, since these nanoparticles are non-oily, easily absorbed. TiO 2 is essentially a UV filter (UVA and UVB filter) hence widely used in sunscreens and moisturizers as well. The well-known cosmetic companies Boots, Avon, The Body Shop, L'Ore´al, Nivea, and Unilever are implementing nanoparticles in the formulations of cosmetics. Along with sunscreens TiO 2 is used in lip balms, foundations, day creams as UV filters so as to protect the skin from the carcinogenic effects of UV radiations. Besides TiO 2 , ZnO, zirconium oxide (ZrO 2 ), Cerium oxide (CeO 2 ) nanoparticles are used in cosmetics as UV filters as the particles are able to scatter and reflect the UV radiations. CeO 2 is able to hinder the UV radiation but not able to produce the Reactive Oxygen Species (ROS) like TiO 2 nanoparticles. Cerium phosphate nanoparticles with low photocatalytic activity showed effectiveness in UV absorption. The better feel and distribution of the cosmetics can be achieved through the use of zinc oxide and titanium oxide nanoparticles. The usual shaped TiO 2 and ZnO nanoparticles execute very useful applications in the cosmetic industry. The most important features for the use of these nanoparticles include their defined size and surface area. This ultimately determines the efficacy of UV filtration in sunscreens [19]. The only distinction between TiO 2 and ZnO is TiO 2 can be used for the UV B diminution while ZnO is a UV A safeguard to protect against aging caused owing to ultraviolet rays. As compared to ZnO, TiO 2 acts as an effective measure to protect against UV B, and hence when sun protection factor (SPF) is concerned TiO 2 is more effective in terms of SPF at a given concentration [20,21].
Titanium dioxide is esteemed for its high refractive index and white coloration, making it advantageous as the most commonly used white pigment. It absorbs UVR because of its semiconductive property. UV absorption is one of the natural features of TiO 2 that can be explained by solid band theory. Both zinc oxide and titanium dioxide nanoparticles are common ingredients of sunscreen. The size can also influence the efficacy of nanoparticles used in cosmetics. As per the study, TiO 2 nanoparticles are effective in UV B and ZnO nanoparticles are efficient in UV A. These microsized particles are effective as sun protection factors. The size reduction in the particles of TiO 2 and ZnO enhances the UV absorption at the expense of UVA1 as a result UV protection becomes unbalanced. This can be overcome through a combination of diverse ZnO microsized particles (∼200 nm or minor to preserve transparency) and nanosized TiO 2 . Further studies reveal that the combinations of two different grades of zinc oxide nanoparticles are used for cosmetic formulations. Studies in this area reveal that further optimization results in the combination of two grades of ZnO particles (dispersed in Cyclopentasiloxane or isononyl isononanoate) with slightly whitened 35 nm TiO 2 NPs offering better UVB protection. The balanced UVA and UVB protection can be achieved through the ZnO dispersions of small nanosized and large microsized particles. This research explains that aggregated ZnO particles of dimension 130 nm rather than the 20 nm primary particles influence UVA-1 protection [22,23]. The fabrications of polyacrylonitrile (PAN) nanofibers which are associated with the UV protection property are possible with various concentrations of multi-walled carbon nanotubes (MWCNT) and TiO 2 nanoparticles. The hybrid of MWCNT and TiO 2 nanoparticles resulted in excellent activity in the UV blockage [24].
The presence of non-cytotoxicity, biocompatibility, and stability of gold nanoparticles make gold nanoparticles significantly useful in cosmetic formulations [25,26]. Presently there is a lot of debate about AuNPs cytotoxicity, as it depends on the variety of parameters such as size, shapes, cell lines used in toxicity assays, concentrations and coatings of nanoparticles, incubation time, synthesis method, surface functionalization [27][28][29]. It is found that AuNPs in concentration between 1 and 67 μM/L are not cytotoxic to Hep3B (hepatocellular carcinoma) and Panc-1 (pancreatic epithelioid carcinoma) cells [27]. In another study, it was revealed that 10 and 50 nm citrate-coated AuNPs did not show toxicity towards embryonic fibroblast cells [28]. Besides these characteristics, the antifungal and antibacterial nature of gold nanoparticles is also beneficial. Gold nanoparticles have been employed in various cosmetic products such as skin wound disinfection, antiinflammatory creams and lotions, face packs, and anti-aging creams. Gold nanoparticles in cosmetic products offer numerous benefits such as antiseptic and anti-inflammatory properties, enhanced blood flow, acts as antiaging, making the skin more elastic and firm, and energizing skin metabolism. As the skin gets exposed to various factors such as pollution, smoke, harmful sunlight rays it results in the formation of ROS. Excessively produced ROS are able to damage healthy cells and tissues. This may affect the different macromolecules of cells such as DNA and RNA [11]. Therefore, antioxidants present in cosmetics can protect the skin. The green synthesis of gold nanoparticles by using Hubertia ambavilla plant exhibited that gold nanoparticles are biocompatible in nature as these nanoparticles are non-toxic to human dermal fibroblasts, ability to scavenge free radicals and impart UVA protection to fibroblast and dermal cells [30]. The safety of gold nanoparticles in the cosmetics was determined through various tests such as acute toxicity test, skin sensitization potential of AuNPs, irritation of the skin and eyes. Genotoxicity of AuNPs was reported as nonphototoxic, nongenotoxic, non-irritant and non-sensitizing according to OECD guidelines. These results suggest that green AuNP is a promising ingredient for cosmetic applications.
The eco-friendly synthesis of gold nanoparticles is achieved through the Punica granatum juice which is valuable in cosmetic preparations [31]. The pomegranate juice contains different alkaloids and polyphenols. The ellagic acid present in the pomegranate juice, which has the ability to protect the cells from free radical damage. Along with this, anthocyanidins also have a vital role in free radical scavenging. Therefore, these antioxidants play a very important role in cosmetic formulations. Punicalagins of pomegranate revealed the presence of free radical scavenging capacity. These components are water-soluble and high bioavailability.
The nanoparticles present in cosmetic products can behave as active ingredients, carriers, consistencyenhancing components, improving the efficacy of cosmetic products. Besides, the silver nanoparticles are also utilized in cosmetic formulations because of the broad antimicrobial activities of silver nanoparticles as well as the property of acting as a preservative. The creams containing silver nanoparticles have antimicrobial activity and hence they can be used as a skin and wound disinfectant [32]. There has been the utilization of silver nanoparticles in toothpaste and shampoos as preservatives. This benefits the treatment of dandruff, itchy and oily scalp [33]. AgNPs have also been popular in dental materials because of the unique properties of nanoparticles [34]. The use of silver nanoparticles in peel-off face mask formulation was also possible. The bacterial synthesized (Bacillus nakamurai) silver nanoparticles possess antibacterial activity and used in the formation of antibacterial peel-off face mask [35]. Silica nanoparticles are being predominantly used in cosmetics because of their hydrophilic surfaces and economical synthesis. The silica nanoparticles are able to augment the efficacy, evenness and shelf life of cosmetic products. The cosmetic products are also improved for their absorbency. The use of silica nanoparticles in various colouring cosmetics is also useful such as lipsticks. The even distribution of pigments of lipsticks can be made possible by means of silica nanoparticles. The other cosmetics of skin, nails, hair and face utilize silica nanoparticles in order to achieve efficiency of products. The results regarding the safety of silica nanoparticles are contentious, so deeper studies regarding the use of nanoparticles in cosmetics need to be conducted [36].
On that note, there are some types of nanoparticles that are used to study the penetration of nanoparticles through the skin by optical imaging, which is fluorescent in nature. The upconversion nanoparticles are nontoxic, photostable offer high-contrast optical imaging, photoluminescence properties and allows the nanoparticles potentially applicable in biological systems. The coating of upconversion nanoparticles with polymers improves the penetration in the skin as shown in figure 2.
3D tissue engineering constructs (3D TECs) were used to test the cytotoxicity of upconversion nanoparticles having a coating of polymers [37]. Figure 3 gives an idea about the confocal laser scanning microscopy (CLSM) images of interactions of polymer-coated upconversion nanoparticles with the culture of HaCaT monolayer cell lines. The cell lines were exposed to these nanoparticles for 24 h to understand the interaction and uptake of nanoparticles by cells. Polyethyleneimine coated upconversion nanoparticles are taken up by cells within 4hrs as compared to others.
The comparative study of the uptake of upconversion nanoparticles coated with polymers with 3D epidermal TEC was carried out as shown in figure 4 [37]. These TEC cells were treated with the same concentrations of nanoparticles as used in HaCaT cell lines. The internalization of upconversion nanoparticles coated with polymers was found to be lowered as compared to uptake by HaCaT cell lines as shown in figure 4.
When the comparison of results of the 3-(4, 5-Dimethythiazolyl)-2, 5-diphenyl-2H-tetrazolium bromide (MTT) assay of upconversion nanoparticles cytotoxicity in the 3D tissue engineering constructs and monolayer cell cultures of HaCaT cells was done it was found that the viability of cells lines due to PAA and PEG-coated upconversion nanoparticles reduced to 85%, while in case of PEI coated nanoparticles it was decreased upto 65% [37]. Therefore, the PEI-coated upconversion nanoparticles were found to be toxic to the cells. On the contrary, in the case of TEC cells the viability of cells due to PEI coated upconversion nanoparticles; it was increased to 115%. Therefore, these PEI-coated nanoparticles were found to be non-toxic along with PEG and PAA-coated upconversion nanoparticles. Toxicity studies of polymer-coated upconversion nanoparticles were thoroughly studied in 3D tissue engineering constructs. Thus, these upconversion nanoparticles being nontoxic, compatible in nature upconversion nanoparticles can be used as carriers. These nanoparticles enable new methods for cosmetic industries in designing and testing with no animal testing which also becomes costeffective [37].

Nanomaterials used in cosmetics
The synthesis of nanomaterials is possible with the help of nanotechnology [38]. These nanomaterials can be used in cosmetics to impart new characteristics to the cosmetics. The varied types of nanomaterials with various characteristics and may create different benefits. The types of nanomaterials that are used include nanocapsules, dendrimers, nanoemulsions, nanoliposomes, nano-hydroxyapatite materials, which have been used in cosmetics for various purposes such as oral care, protective carriers and delivering ingredients through the skin. The brief outline of their methods of synthesis has been summarised in table 1.

Liposomes
These are spherical double phospholipid membrane-bound molecules. These liposomes can behave as vehicles for the delivery of enclosed desired molecules into or through the skin. These nanomaterials act as a storehouse of desired actives. The uses of liposomes in cosmetics derive various benefits such as non-toxic, biodegradable, flexibility. These liposomes can be used to encapsulate active components for easy and safe delivery. Both   Micro-fluidization Components of the liposomes + distilled water or buffer (Dispersion), Place in the tank of the microfluidizer + air regulator to maintain operating pressure + collect, put the product at above phase transition temp, under inert conditions using N 2 or Ar for 1 h. Noisome Ether injection method Dissolution of surfactant in diethyl ether followed by injection of solution through a 14-gauge needle into an aqueous solution of drug maintained at 60°C. After vaporization of ether single layer vesicles are formed.
50 to 1000 nm [40,41] Thin-film hydration technique Surfactant + cholesterol in a volatile organic solvent, evaporation thin layer deposited on the wall of the flask, hydrated with the desired drug.

to 1000 nm
Reverse-phase evaporation technique The drug in aqueous phase + surfactant and cholesterol in ether or chloroform (1:1), sonication, the addition of phosphate buffer saline, sonication, remove ether or chloroform, suspension heated at 60°C for 10 min. to form niosomes.

to 3610 nm
Dendrimers Divergent method Synthesis gets initiated from the core part of the dendrimer's building blocks at the exterior.
1 nm up to 10 nm [42][43][44] Convergent method The synthesis starts from the exterior part to the core part to form the final dendrimers. Nano-emulsions Microfluidization The solution was passed through an air-driven microfluidizer, 500 ml sample passed through the microfluidizer at the set pressure for 1 cycle. Then one-third part of the microfluidized sample was taken away for size analysis and the remaining volume was again passed through it for the 2 nd and same for the third cycle.

20-200 nm [45]
High Pressure Homogenization 5 wt% lipid phase + 95 wt% aqueous phase 10 mM sodium phosphate buffer premix blending the lipid and aqueous phases together for 2 min at RT coarse emulsions passed through an air-driven microfluidizer at various homogenization pressures [46] Solid lipid nanoparticles (SLN) and Nanostructured lipid carriers (NLCs)

Solvent emulsification-evaporation technique
Drug + core material + coat material + chloroform evaporated in rotary evaporator+ 10 ml PBS+ sonication to form lipid nanoparticles 50nm-1000 nm [47] Microemulsion technique Water+ co-surfactant(s) + surfactant heated to the same temperature as the lipids mild stirring to the lipid melt, mixed in the correct ratios for microemulsion formation.

Chemical Vapour Condensation method
Cobalt carbonyl (Co 2 (CO) 8 ) used as a precursor and carbon monoxide (CO) as a carrier gas in the furnace with temperatures ranging from 400 to 1000°C, nanoparticles formed to form core-shell nanocapsules. [53] Nanotubes Chemical vapour deposition A mixture of xylene and ferrocene, decomposition of the ferrocenexylene mixtures in the temperature range 625-775°C at atmospheric pressure, begin to deposit carbon as well-aligned pure MWNT arrays on the quartz surfaces.

nm [54]
Electrochemical Anodization The electrolyte was 1 M (NH 4 ) 2 SO 4 with small amounts of NH 4 F (0.5-5 wt.%). The electrochemical treatment consisted of a potential ramp from the open-circuit potential (OCP) to 20 V with a different sweep rate followed by holding the applied potential at 20 V for different times. The samples were rinsed with deionized water & dried with an N 2 stream. [55] Nanospheres Solvo-thermal routes Charging of metallic copper powder and CCl 4 into a Teflon-lined cylindrical stainless steel autoclave sealed, heated up to 200°C within 30 min, and maintained at 200°C for 2 h in an oven, cooled, the product collected and treated with HNO 3 for 20 h under ambient conditions stirring. The product recovered by filtration, washed with deionized water dried at 60°C for 10 h.
100-1000 nm [56] hydrophilic and hydrophobic molecules can be delivered through the liposomes. The phospholipids present in the liposomes are able to maintain the softness and smoothness of the skin. The lipids present in the liposomes protect the active ingredients from UV rays and in turn, helps in the enhancement of the shelf life of products [57]. Nanoliposomes and liposomes can be synthesized through the methods of sonication and microfluidization. The very first method of synthesis of liposomes was extrusion. In that process liposomes depending on the pore size of the filters employed and structurally modified to large unilamellar vesicles (LUV) or nanoliposomes [39,58,59]. The hair and skin also get protected from the UV rays because of liposomes. The release of the active ingredients at the site can be possible with the help of liposomes. The different types of components such as vitamins, antioxidants and other lipid molecules can be delivered with the help of liposomes. 'Capture' was the first liposomal anti-aging cream launched by Dior in 1986 [60]. Cosmetic products such as creams, shaving materials, sunscreens, shampoos implement these liposomes. The phosphatidylcholine type of phospholipid present in liposomes can soften and condition due to which these can be used in various shampoos and conditioners. The oxidation of liposomes may cause quality deterioration of liposomes.

Noisome
These are nano-vesicles made of self-assembly of essentially non-ionic surfactants [61], with or without the incorporation of cholesterol or lipids. These vesicles can be unilamellar (0.025-0.05 μm) or multilamellar (more than > 0.05 μm) containing aqueous solutions of solutes and the membrane formed by the arrangement of surfactant molecules to form bilayer [40,62]. The different components of noisome such as cholesterol and nonionic surfactants are widely used [61]. Niosomes are formed by non-ionic surfactants which were first established by Handjani-Vila et al. The widely used methods for the synthesis of niosomes are ether injection method, film method, sonication method of Handjani-Vila, reverse-phase evaporation and heating method [40,63]. The scientists from L'Oréal (Clichy, France) were applied noisome in cosmetic formulations in the 1970s and 1980s. Along with the cosmetic applications, these were utilized in various other sectors such as pharmaceuticals, and food [64]. The bioavailability of actives can be higher with the help of noisome. Therefore, these can be considered as drug delivery vehicles [65,66]. The various parameters such as structure, type of surfactants, nature of encapsulated drug and temperature can affect the synthesis of noisome [67]. Along with noisome, proniosomes are used in order to get improved drug delivery vehicles [68]. The moisturizers and skin whitening creams, anti-wrinkle creams, shampoos and conditioners have also been formulated through noisome [41,69,70].

Dendrimers
These are monodispersed, unimolecular and nanostructures with the dimensions of 20 nm. The presence of a total number of series of branches determines the generation of dendrimers [71]. The 1st generation dendrimer has one series of branches; in the case of 2 nd generation dendrimers, there are two series of branches. These are used as vehicles for the slow, controlled delivery of active ingredients at the desired site. The particles are symmetrical in nature with various functional groups at the circumference of particles. These functional groups act as the site of attachment for the various chemical components. The surface of dendrimers can act as carriers for the various external functional groups. In 1985, the Newkome dendrimers were one of the first artificially synthesized dendrimers. The synthesis of dendrimers is possible with two mechanisms as a divergent method or a convergent method. The divergent method of synthesis gets initiated from the core part of the dendrimers followed by the addition of building blocks at the exterior. While latter includes vice versa as that of the divergent method in which the synthesis starts from the exterior part that ultimately becomes the outermost arm of the final dendrimer [42][43][44]. There are several cosmetic companies that patented the usage of dendrimers in various products of skin, hair, nail [72]. Because of such characteristics of the dendrimers, both hydrophilic and hydrophobic molecules are enclosed into dendrimers [73]. These nanostructures have been used in different cosmetic products such as sunscreens, shampoos, anti-acne creams, and hair-styling materials. The cosmetic companies such as Dow Chemical Company, L'Oréal, Revlon, and Unilever, have registered patents on dendrimer-dependent cosmetic preparations for various applications for skin, nail, and hair care products.

Nanoemulsions
Nanoemulsions comprising nanoparticles in the range of 50 to 1000 nm and it is also a mixture of oil and water. These nanoemulsions are used in various hair sunscreens, shampoos, skin and deodorants. Korres' Red Vine Hair sunscreen cosmetic company uses nanoemulsions [74,75]. The nanoemulsions impart various properties to the cosmetics such as improvement in the shelf life of products and texture. These nanoemulsions act as carriers for various lipid compounds like liposomes. The nanoemulsions are able to reduce the delicacy and oily nature of hair making the hair shiny. They are considered safe. These are basically used in the sprayable form.
The presence of characteristic properties such as high surface area, minimal viscosity, stability, solubility makes the increased usage of nanoemulsions. Nanoemulsion synthesis involves a two-step process where a macroemulsion was first prepared and then converted to a nanoemulsion in a second step. The synthesis of nanoemulsions is broadly classified as high and low-energy methods. Microfluidization, high-pressure homogenization (HPH), evaporative ripening method proposed by Fryd and Mason, bubble bursting at an oil/ water interface are some of the methods used for nanoemulsions synthesis [45,76,46]. The nanoemulsions are extensively used in sunscreen, deodorant, nail enamels, body lotions, hair conditioners and shampoos and hair serums [77]. The use of nanoemulsions in cosmetic products has been increased because of small dimensions of particles that would definitely be helpful in the enhanced skin penetrations, improved skin hydrations, presence of increased fluidity with a glossy coating of skin with improved infiltrations of active ingredients through the skin.

Solid lipid nanoparticles (SLN) and Nanostructured lipid carriers (NLCs)
The solid lipid nanoparticles (SLN) are of sub-micrometer in dimensions. These nanoparticles are made of a unique outer shell in which oily or lipid materials are present as a core. These are of polymeric in nature contain different types of fatty acids such as stearic acid or a mixture of fatty acids [78][79][80][81]. When the structure of the skin is considered, it is composed of the outer epidermis which covers the layer of the dermis which confines blood and lymph vessels. The use of SLN for the skin becomes appropriate as the nanoparticles contain lipid particles which allow the easy absorption of these nanoparticles through topical applications. The SLN being hydrophobic in nature, the particles are able to protect the skin from dehydration and to maintain the moisture of the skin. Therefore, these nanoparticles have better skin penetration, non-toxicity and effective carrier. These nanoparticles are able to liberate the active components instead of deeper penetration through the skin. SLN and NLC (Nanostructured Lipid Carrier) are widely used as carriers for sunscreens, anti-acne and anti-aging components [82][83][84]. These lipid nanoparticles are promising carrier systems as compared to conventionally used carriers such as nanoemulsions, liposomes. SLN and NLCs show many beneficial features such as the controlled release of actives, occlusion, and increased skin hydration effect for cosmetic applications. These are considered as a 'nanosafe' carrier system that has negligible cytotoxicity and remarkable tolerance as these are made of biodegradable and physiological lipids. Different methods for the synthesis of lipid nanoparticles are reported such as using a high-pressure homogenization process. Ultrasound is another method for preparing lipid nanoparticles using high energy. Techniques based on microemulsions, double emulsion formation, phase inversion induced by temperature, membrane contactor and cold homogenization are a few of the most studied in this regard. Solvent emulsification-evaporation technique, solvent emulsification diffusion technique, high shear homogenization and/or ultrasonication technique are also widely used methods for their synthesis [47,85,86]. The presence of high absorbance, stability makes the NLCs greater than SLNs in cosmetic products. These lipid nanoparticles are able to penetrate the skin more efficiently. The colourless lipid particles improve the appearance of cosmetic products. Nanorepair cream was the first cosmetic product containing these lipid particles in 2005. The skin lotion of Dr. Rimpler GmbH, Germany, improved skin penetration using NLCs [87,88].

Fullerenes
These fullerenes contain carbon rings of odd numbers of three-dimensional spherical nanostructures [89,90]. These are like cage structures. The discovery of fullerenes won a Nobel Prize and from which the nanotechnology field launched. Synthesis of fullerenes by vaporization of a carbon source, laser vaporization of carbon in an inert atmosphere, electric arc heating of graphite, laser irradiation of polycyclic hydrocarbons (PAHs) and resistive arc heating of graphite are reported [48,49].
Carbon fullerenes are able to forage the free radicals and also able to rejuvenate the skin. These are mainly hydrophobic in nature and difficult to get solubilized but when they are attached with other molecules like surfactants these can be solubilized and can be applied in various cosmetic formulations. The carboxy-fullerenes are able to protect the keratinocytes from UVB-induced damages. 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].

Nano-hydroxyapatite
Nano-hydroxyapatite is mainly used in oral care products as well as cosmetic products. In dental care, hydroxyapatite is used for remineralization and in case of hypersensitivity. Various oral care products have included these nanohydroxyapatite nanomaterials in dentifrices and mouthwashes, and because of remineralization and desensitization nature, nano-hydroxyapatite can be a substitute for fluoride toothpaste [94][95][96]. Microwave-assisted preparation of nano-hydroxyapatite for bone substitutes, wet chemical precipitation technique, ultrasound-assisted method, surfactant-assisted synthesis, and sol-gel technique is employed for the synthesis of nano-hydroxyapatite [97,50,51,98,99].

Nanocapsules
These are used in cosmetics in order to protect vital actives as these are confined by an oily or water state. The polymeric forms of nanocapsules in the form of suspensions can be used on the skin and these are used to encapsulate the different components. The modifications of nanocapsules can also be achieved through the type of polymer and surfactants used. The stable forms of nanocapsules of dimensions 115 nm can be achieved through the use of poly-l-lactic acid by nanoprecipitation. These nanocapsules have entrapped with fragrant molecules that make the continuous release of perfume. Thus, these nanocapsules are biocompatible in nature and are used in various deodorants. The entrapment of jasmine essence in the γ-polyglutamic acid/quitosans could release the fragrance in a sustained manner [100]. Various methods such as surfactant-assisted, miniemulsion polymerization techniques, chemical vapour condensation process have been employed for the synthesis of nanocapsules [52,53]. For the first time, L'Ore´al named cosmetic company in 1995 initiated the use of nanocapsules dependent cosmetic products [101]. These nanocapsules can be used for the entrapment of both hydrophobic and hydrophilic types of carriers. The surfaces of nanocapsules can be attached with proteins, polymers and biomolecules. These nanocapsules are stable in an aqueous medium, biodegradable and biocompatible in nature [102][103][104][105][106][107]. The polymers attached with nanocapsules affect the dimensions of particles. These particles are biocompatible in nature and get degraded into CO 2 and water. These products can be excreted from the body. The nanocapsules are used as a carrier for the antioxidant components which are helpful in anti-aging cosmetic formulations [108].

Nanotubes
The graphene-based nanomaterials have been implemented in various hair colouring agents. The attachments of different polymers with the nanomaterials produce coloured products. This combination of polymers and nanomaterials resulted in the formation of highly resistant hair coloures, thus cannot be washed easily with shampoos. Carbon nanotubes (CNTs) are the rolled graphene, hollow, cylindrical fibers and are made of graphene walls, cylindrical hollow fibers, and composed of graphene walls. CNTs are highly light in weight and with dimensions of 0.7 to 50 nm in diameter, with lengths of approximately 10 s of microns [109]. There are different types of CNTs like single-walled, double-walled, and multi-walled CNTs. Single-walled CNTs contain a single sheet of graphene, the double-walled CNTs have two concentric single-walled CNTs. The multiple layers of graphene tubes lead to form multi-walled CNTs [110]. Carbon nanoparticles, CNTs, and peptide-based CNTs are used in cosmetics preparations [108,109]. Chemically modified CNTs are applied for coloring hair, eyelashes, or eyebrows [110]. Peptide-based CNTs synthesized by integrating a hair-binding peptide on the surface of the nanotube, increase the affinity to hair by covalent bonding. Halloysite clay nanotubes, nickel vanadate nanotubes, and boron-nitride nanotubes are also utilized in hair care formulations. Chemical vapor deposition (CVD), electrochemical anodization processes have also been widely used methods for the fabrication of carbon nanotubes [54,55]. It is due to the high abundance in nature, minimal toxicity and economic nanoclay nanotubes have high demand in hair care products [111][112][113].

Nanospheres
The nanospheres are bounded by a polymeric matrix with the spherical nature of the matrix of 10 to 200 nm. These are amorphous and crystalline in nature. There can be both biodegradable and non-biodegradable nanospheres. Albumin, pristine-based nanospheres along with modified starch or gelatine-based nanospheres are mainly biodegradable in nature while polylactic acid (PLA) presents the non-biodegradable type of nanospheres. The deep delivery of active ingredients present in cosmetics can be achieved through nanospheres. This system makes an efficient and precise delivery of actives present in cosmetics. The anti-acne, anti-wrinkle, and moisturizing creams are included with the nanospheres [114][115][116]. Ubiquinone (UQ) containing poly-(lactide-co-glycolic acid) (PLGA) nanospheres are being stable, efficient and have the ability to control the release of actives present in the cosmetics. The nanospheres can also be synthesized by catalytically assisted chemical vapour deposition (CCVD), hydrothermal routes and reduction mechanism [56,117,118].

Types of nanotechnology-based cosmetics
Various nanomaterials have been reportedly used in the production of different formulations, aiding packaging as well as technology for manufacturing units in the field of cosmetics by virtue of their multi-faceted properties. Nanomaterials-based approaches have been widely used in cosmetics by virtue of their diversified interactions with different tissues like skin, hair, teeth, etc [8]. Nanotechnology-based formulations have been immensely used in different beauty products, skincare products as well as sunscreens, hair care products, deodorants and perfumes in addition to dental products as a result of associated advantages like enhanced performance and high bio-availability [119].

Beauty products
Different nanoparticles have been reportedly used in various beauty products such as fairness creams, concealers, foundations, makeup bases, lipsticks, etc by virtue of their physico-chemical, electronic as well as optical properties [4]. For example, gold and silver nanoparticles have been exploited in different cosmetic compositions on the basis of their optical properties. Gold nanoparticles have been used for red or blue coloration; silver nanoparticles for yellowish coloration as well as gold-silver nanocomposites have been used for orange coloration [120]. In addition to this, nanoparticles have been successfully used in the modulation of skin colour. This approach makes use of blending techniques using formulations having nanoparticles that establish the original skin colour initially followed by the desired skin colour. For example, silver nanoparticles resulting in blue coloration are used to set the initial skin colour followed by complimenting silver nanoparticles with gold nanoparticles which give green colour collectively contributing to a brighter shade. Depending upon the skin type and colour, nanoparticles used have been selected [121]. Solid lipid nanoparticles have been used in skin whitening formulations for topical delivery of active ingredients like 6-methyl-3-phenethyl-3,4-dihydro-1Hquinazoline-2-thione (JSH18) which is effective in skin lightening due to its property of tyrosinase inhibition crucial for melanin production. Application of JSH18 containing SLN formulations has shown effective recovery of skin coloration in hairless rats within 4 days post-exposure to UV irradiation for a time period of 7 days thus suggesting its potential applicability in skin whitening [122]. Both forms of arbutin, i.e., α-arbutin and βarbutin, have been immensely used in beauty products because of their hyperpigmentation and antioxidant properties. Chitosan nanoparticles have been used for entrapping α-arbutin and βarbutin. These chitosan NPs entrapped α and βarbutin have been observed to show higher stability and greater bioavailability as compared to their free forms thus proving chitosan NPs a promising carrier for topical delivery in skin whitening formulations [123,124].
Apart from skincare products, nanoparticles have also been used in lip care as well as nail care products. Different nanoparticles have been incorporated in lip balms, lip gloss and lipstick in order to trap the moisture within the lips thereby retaining its softness. For example, silver and gold nanoparticles have been used in different ratios depending on the desired colour for long-lasting colour retention [125]. Silica nanoparticles have also been used in lip care products to ensure high coverage as well as even distribution [126]. Moreover, nail care products containing nanoparticles impart benefits like enhanced toughness as well as resistance to blemishes in comparison with traditional counterparts [127]. The nail colour incorporated with nanoparticles developed by Nano Labs Corp. has been associated with different advantages like easy drying, shock resistance, elimination of cracks and scratches as well as easy application. The future beholds the use of nail care products with nanoparticles having antimicrobial properties to be used in treating microbial infections thereby serving aesthetic as well as therapeutic purposes [128].

Hair products
Nanotechnology-based technology has been extensively used in various hair care products such as hair shampoos, hair conditioners, hair colour, hair serums, hair sprays as well as other hair styling products. The use of nanoparticles has been employed in order to facilitate the prevention of hair loss, treatment of hair-related issues, enhancement of hair growth, enrichment of hair quality, etc. Out of different nanoparticles used, nanospheres, nanoliposomes as well as nanoemulsions have shown promising results in hair care as compared to conventional hair care products [129]. In another study, sericin nanoparticles which have been prepared using sericin protein extracted from the cocoons of silkworm Bombyx mori have been used in hair care products after functionalization using quaternary ammonium salts thus forming sericin cationic nanoparticles. These nanoparticles which have been intended to be used in the repair of damaged coloured hair have shown promising results by promoting hair shine, softness, tangibility thereby restoring hair health in addition to maintenance of hair colour [130]. Polymeric nanoparticles have been reported to be used for follicular drug delivery which can be used to treated hair problems. Roxithromycin (ROX) loaded pluronic lecithin organogel (PLO) have been used against hair loss problem because of its hair restoration property. Efficient penetration of ROX-loaded PLO into the hair follicles has been confirmed by fluorescence tracking which in turn increases the effectivity of these nanoparticles-based hair formulations in treating hair loss [131].
Different metal nanoparticles, metal oxide nanoparticles, carbon-based nanoparticles as well as quantum dots have been used in hair colour in order to improve the retention of hair colour along with its manageability. Metallic nanoparticles such as silver, gold, copper, palladium, platinum, selenium, cadmium, etc along with their alloys have been used in hair colouring products. These metallic nanoparticles with a coated layers of organosulfur compounds have been observed to improve hair quality, help in hair-dressing, enhance hair conditioning as well as impart protection against heat and solar radiations [132]. Carbon nanotubes with chemical and physical modifications have also been used in hair coloring. The use of carbon nanotubes has been observed to impart black color to human hair without damaging it. These CNTs-based hair colour forms a thin layer upon human hair by virtue of its small size thus imparting smooth texture as well as voluminizing them. The high surface area to volume ratio increases retention of CNT-based hair colour as compared to conventional hair dyes [133,134].

Skin products
Different skincare products like sunscreens, moisturizers, skin cleansers, anti-aging formulations, etc make use of biomolecules such as antioxidants, proteins and vitamins by virtue of their anti-aging properties. The use of nanoparticles, nanoemulsions as well as solid lipid nanoparticles provides a greater advantage over conventional skincare products by increasing the bioavailability of the active ingredients in addition to enhancement of other cosmetic benefits. Metal-based nanoparticles have been exploited for their antioxidant properties thereby nullifying the effect of free radicals contributing to anti-aging. For example, cerium oxide nanoparticles loaded liposomes have been used in anti-aging creams in order to minimize the adverse effects caused for the generation of free radicals thereby promoting tissue longevity [135]. Solid lipid nanoparticles (SLNs), as well as nanostructured lipid carriers (NLCs), have been widely used in transdermal drug delivery. SLNs loaded with different antioxidants like resveratrol, vitamin E (VE), and epigallocatechin Gallate (EGCG) have been observed to provide excellent skin protection. SLNs ensured a controlled release profile in case of resveratrol upto 70% in a time period of 24 hrs thereby increasing its bioavailability. Moreover, resveratrol encapsulated SLNs showed more efficient penetration into stratum corneum thus suggesting to be a promising alternative to be used in skincare products due to its lasting antioxidant properties [136].
Nanoemulsions have been used in cosmetic applications aiding delivery of active ingredients with issues in storage, solubility, stability, loss of activity, etc. Nanoemulsions have been reported to be synthesized using the phase inversion emulsification method using rice bran oil along with sorbitan oleate and castor oil mixture thereby providing a moisturizer with high stability and low irritability. These nanoemulsions provide excellent antioxidant properties due to the presence of tocopherols and gamma-oryzanol in addition to superior hydration properties in comparison with conventional moisturizers [137]. Sunscreens make use of metal oxide nanoparticles like zinc oxide and titanium dioxide with intrinsic properties to absorb UV irradiation. These nanoparticles scatter UV light thereby preventing its harmful effect on the skin. In addition to this, these nanoparticles show inherent biocompatibility upon interaction with dermal tissues due to which they have been widely used in sunscreens with excellent efficiency [138].

Oral products
Nanotechnology-based approaches have been used in various oral care products like toothpaste, toothbrushes, mouthwashes, dental floss, etc so as to improve the efficacy of the product as compared to its traditional counterparts. Different types of nanocarriers such as nanoparticles, liposomes, quantum dots, polymers, hydrogels as well as dendrimers have been used for this purpose. Toothpaste containing nanomaterials helps in improving tooth healing and rebuilding of enamel by facilitating remineralization, fixing tooth sensitivity as well as help to fight dental problems against bacterial infections. Different nanoparticles such as silver, gold, zinc oxide, titania, calcium carbonate, hydroxyapatite, etc have been known to be exploited in oral care [139]. Use of bioactive non-stoichiometric hydroxyapatite nanoparticles substituted using carbonates in dental formulations has been reported. These nanoparticles are 20-200 nm long, 5-30 nm wide in addition to crystalline nature less than 40% with an aspect ratio within the range of 2 to 40. The dental formulations containing hydroxyapatite nanoparticles facilitate efficient tooth desensitization as well as remineralization in a time frame that can be devoted to routine oral care. The use of hydroxyapatite nanoparticles also increases the shelf life upto 2-3 months due to its stable nature [140]. Zinc nanoparticles in non-aggregated form have been reported to be used in oral composition with anti-plaque as well as anti-malodor benefits. The use of zinc ions in the form of its nanoparticles further reduces the total amount of zinc present in the composition thereby enhancing its negative organoleptic characteristics as well as improving the clarity of the oral formulation [141].
The most commonly occurring oral diseases like dental caries as well as periodontal diseases are attributed to a remarkable increase in microbial load [142]. These problems can be managed preliminarily by using oral care products containing nanoparticles with antimicrobial properties. Silver nanoparticles have been reported to show excellent antimicrobial activity against multiple aerobic and anaerobic oral pathogens like Escherichia coli, Aggregatibacter actinomycetemcomitans, Fusobacterium nuceatum, Streptococcus mitis, Streptococcus mutans as well as Streptococcus sanguinis in a size-dependent manner. Thus, the use of silver nanoparticles in dental formulations can aid in controlling microbial infections selectively by virtue of its high antimicrobial activity as well as biocompatibility against human cells [143]. Gutta-percha (GP) which has been used as a dental filler during root canal therapy gives rise to problems like leakage, dental reinfection as well as sub-standard mechanical properties. These shortcomings can be over by using GP embedded nanodiamonds which show excellent mechanical properties as well as high biocompatibility thereby making them suitable for dental applications. Moreover, functionalization of these GP embedded nanodiamonds with traditional antibiotics specific for oral infections such as amoxicillin further enhances its applicability in dental treatments with excellent results [144].

Pros of use of nanomaterials in cosmetics
The various types of nanoparticles titanium dioxide (TiO 2 ), zinc oxide (ZnO), silver, silicon dioxide, gold nanoparticles have been utilized in cosmetics [145][146][147][148][149][150]. The main purpose of the use of nanoparticles in cosmetics is that the nanoparticles affect the efficiency of the products, shelf life of products. The use of zinc oxide and titanium oxide as UV blockers is more beneficial than that of Avobenzone, a compound present in sunscreens. The compound is found to be very greasy and noticeable when applied. However, the ZnO and TiO 2 nanoparticles are non-oily, odourless and colourless nanoparticles which are better UV blockers and do not form any kind of white residue upon application on the skin. This is the main reason for the extensive use of zinc oxide and titanium dioxide nanoparticles in sunscreens. The evenness to the cosmetics creams can be offered by the incorporated nanoparticles along with full and even coverage of the skin.
There is a wide usage of nanoparticles in anti-aging products because of their carrier nature [151,152]. The delivery of antioxidants to the skin could be possible with the help of these carriers. The topical administration of retinoids, antioxidants, for rejuvenation of the skin can be achieved through the field of nanotechnology as most of the components cannot pass through the skin.
Some of the benefits of the use of nanoparticles in cosmetics are listed as follows

Cons of use of nanomaterials in the cosmetic products
The presence of high reactivity of nanomaterials because of the high surface to volume ratio gives rise to toxicity. These various properties of nanoparticles can be acquired through the reduction of dimensions of particles. These nanomaterials are able to catalyze various reactions and cause toxic effects. This leads to the increased penetration of nanoparticles through the skin and affects the cells of the human body. Therefore, the use of nanomaterials is a double-edged sword as the nanomaterials are useful for medical purposes, but result in far penetration of nanomaterials that exert an adverse health effect. Regardless of the various benefits of nanoparticles in cosmetics, there are strong apprehensions with respect to the safety of nanoparticles in cosmetic products. This jeopardy is not only related to the consumers but also to the workers which are in daily contact with these nanoparticles [153][154][155][156][157].
As every coin has two sides, the use of nanoparticles in cosmetics also has both advantages and disadvantages. As the nanomaterials possess different characteristics as compared to bulk materials, they might be able to alter the biological properties. Therefore, a study related to the toxicity of nanoparticles is warranted. The evaluation of the influence of size, morphology, charge, interactions of particles with the biological cells and correlations with toxicity and safety issues afford no consensus to date. Because of the presence of unique features of nanoparticles, they are exploited in various applications. Conversely, these characteristics are hypothesized to be the basis for nanoparticles induced toxicity which arises due to the complex interplay between nanoparticle uniqueness (e.g. size, shape, surface chemistry and charge), administered dosage and host immunity. Changes in these attributes may influence interactions of nanoparticles with biomolecules, proteins, cell lines, and tissues. It is imperative to assess the intracellular activity and function of nanoparticles, for the development of effective and safe nanoparticles to be used in cosmetics [158][159][160][161][162][163][164][165].
The presence of nanoparticles is found to be more reactive which results in the production of huge numbers of ROSs. The nanosized particles can cross different barriers of the human body and affect different systems of the human body including blood, respiratory system, skin. These ROS affects the macromolecules present in the cells such as proteins, DNA even the cell membranes. The nanoparticles could be toxic to human cells and tissues because of which cell death can take place [166][167][168]. The widely used TiO 2 nanoparticles have effects on the DNA of cells as the particles tend to produce ROS which increases the oxidative stress of the cells of fibroblast. The skin fibroblast cells, as well as nucleic acids, get affected due to photo-activated TiO 2 nanoparticles [169]. Titanium dioxide and zinc oxide nanoparticles are able to absorb UV radiations and produce free radicals which affect the skin. This may lead to cell damage and skin cancer. Along with the size of nanoparticles, the chemical nature of nanoparticles also affects the human system. When the rats were administered with nanoparticles by instillation the lungs of rats revealed some inflammatory signs and consequently, the tumours were observed in the lungs. The risk of nanoparticles can depend upon the hazard and the exposure [170]. When pregnant mice were exposed to TiO 2 nanoparticles male offspring caused brain damage. In the long term, the traces of TiO 2 affect the brain [171]. When the cosmetics are taken into consideration, the way of exposure, by the topical application cannot cause this kind of exposure (inhalation) necessary to cause such kinds of damages. It was observed when the mode of application gets changed to aerosols. Crossing the skin barrier and entering into the bloodstream is the main concern in the case of cosmetics. The nanoparticles are able to deliver actives present in cosmetics into the deeper layers of skin. These chemicals may cause irritation. Along with beneficial effects, the adverse effects of nanomaterials on the cells have been studied. The aluminium oxide and iron oxide were investigated for their in vitro toxic effects. The free radicals generated from aluminium oxide nanoparticles were investigated for their induced concentration-dependent stem cell toxicity and produced inflammation that may lead to diseases such as atherosclerosis disrupted the blood-brain barrier and directly toxic to brain blood vessel cells [172][173][174].
The benefits of the use of nanoparticles are usually depicted. However, the risks, health and environmental hazards are caused due to exposure to nanoparticles which are not fully understood [175]. When the nanoparticles are absorbed through the skin, skin, pulmonary tract, brain, and other organs (via blood) damage can result. Some of the nanoparticles affect the brain and raise some perilous effects. The present knowledge regarding the safety of nanoparticles is insufficient. There is a need for research that focuses on the synthesis methods, characteristics, safety assessments in both in vitro and in vivo models, dosage determinations likewise.
The components of cosmetic products should be safe to use and the products need to be mentioned as safe for usage. FDA plays the role of approval of specific products into the market. The cosmetic products used should be in pure and active forms without any adulterations. In this regard, FDA has separate safety guidelines as 'Guidance for Industry: Safety of Nanomaterials in Cosmetic Products' for the usage of nanomaterials in cosmetics [176]. This document gives an idea about the safety concerns of nanomaterials in cosmetics and proposes to support interested companies in the recognition of significant safety measures and their evaluation ways.
6. Toxicity issues 6.1. Human safety issues The extensive use of nanomaterials in cosmetic products has been attributed to its multi-faceted nature. The use of lipid and polymeric nanoparticles as delivery systems has been preferred because its biocompatible nature as well as their ease of biodegradation. However, there do exist toxicity factors upon interaction with the human body which should be taken into consideration while using nanomaterials so abundantly in the cosmetic industry [177,178]. For example, implications of the use of metal-based nanoparticles in cosmetic products on human health have been reported. Traces of different metal nanoparticles such as copper, iron, cobalt, nickel, chromium, cadmium, lead, arsenic, mercury, etc have been detected in cosmetics which pose a severe threat to human health. It is due to their small size, these nanoparticles can easily penetrate through the dermal tissue thereby entering blood via which it can reach almost every vital organ leading to a much severe response after its accumulation [179]. In another study, the effect of polyvinylpyrrolidone-functionalized silver nanoparticles of size 15 nm on human keratinocytes has been evaluated. It is observed that exposure to silver nanoparticles remarkably decreases cell viability, metabolic rate as well as severely impairs its migration and proliferation. Furthermore, prolonged exposure of silver nanoparticles results in caspase 3/7 activation and DNA damage thereby triggering genotoxicity as well as cytotoxicity [180].
Metal oxide nanoparticles such as zinc oxide and titanium dioxide nanoparticles have been extensively used in cosmetics, especially in skincare products owing to their UV blocking properties. Effect of TiO 2 nanoparticles on penetration and cytotoxicity upon interaction with skin cells have been studied Evaluation of skin penetration of TiO 2 nanoparticles using in vivo studies shows penetration through a dermal layer which further invades tissue causing pathological lesions in various organs thus causing a systemic response [181]. Toxicity associated with exposure to ZnO nanoparticles has also been extensively studied. Prolonged exposure of human keratinocytes to ZnO nanoparticles has been associated with reduced mitochondrial function, changes in cellular morphology, free radical production as well as alterations in cell cycle profiles which collectively contribute to decreasing in cell viability. Thus, it is critical to consider toxicity effects upon exposure to the human body while using nanotechnology-based cosmetics [182]. However, there do exist several ways using which toxicity of nanoparticles can be dramatically reduced. For example, TiO 2 nanoparticles coated with fatty acids like palmitoleic acid, oleic acid, palmitic acid, stearic acid, etc show a dramatic decrease in cytotoxicity as well as cell penetration in humans fibroblast skin cells as well as adenocarcinoma lung cells in comparison with bare TiO 2 nanoparticles [183]. Thus, the presence of fatty acids does protect human cells from nanoparticle cytotoxicity which can in turn be exploited while using nanoparticles in the cosmetic industry. Moreover, further research focusing on newer ways to reduce nanoparticle toxicity should be undertaken which in turn would increase its applicability in the cosmetic industry.

Environmental safety issues
The environmental impact of the use of nanomaterials in the cosmetic industry is tremendous as it would contribute significantly to the generation of global nanowastes which is followed by disposal-related problems as well as the risks it poses to the environment considering their long term management. The discarded nanowastes can contaminate groundwater by penetration through wastewater treatment plants and landfills severely affecting the process [21]. For example, silver nanoparticles have been reported to show excellent antibacterial activities against Staphylococcus aureus and Escherichia coli. Silver nanoparticles have been observed to physically interact with bacteria resulting in pit formation thereby causing increased membrane permeability which further causes leakage of vital components ultimately resulting in cell death [184]. Such bactericidal properties of nanoparticles would severely hamper wastewater management, especially the ones employing microbial communities for the removal of organic wastes.
ZnO and TiO 2 nanoparticles which are extensively used in skincare products as UV blockers are also known for ROS generation after photoexcitation. The presence of ROS in the environment has been observed to be harmful to phytoplanktons thereby causing serious damage to the aquatic ecosystem. Exposure to TiO 2 nanoparticles for a prolonged period of 21 days has been observed to decrease the proportion of viable embryos in zebrafish thereby affecting its reproduction severely [185]. Similarly, anatase and rutile forms of TiO 2 nanoparticles have shown reduced cell viability as well as a decrease in chlorophyll content in freshwater microalgae Chlorella sp. following exposure to UV irradiation. Damaged nucleus and cell membranes were observed post interaction with anatase TiO 2 whereas rutile TiO 2 caused damage to chloroplasts as well as other cell organelles [186]. ZnO nanoparticles are also known to cause toxic effects in freshwater white suckerfish, Catostomus commersonii by causing damage to its gill epithelium by affecting cardiovascular regulation due to impaired acetylcholine signaling followed by problems in oxygen uptake attributed to ROS generation [187]. Assessment of toxicity of silver and TiO 2 nanoparticles against planktonic crustacean, Daphnia magna via behavioural and biochemical studies post-exposure. It has been observed that there were remarkable effects on behavioural patterns upon exposure to ASTM-dispersed silver nanoparticles. Also, silver nanoparticles present in the wastewater were found to show higher toxicity in comparison with TiO 2 nanoparticles from the wastewater as well [188]. Thus, there is a need to study the impact of environmental hazards in detail before commercialization of their use in the cosmetic industry.

Future perspectives
The cosmetic industry makes wide usages of nanomaterials for various purposes such as UV filters, preservatives. The characteristic properties of nanomaterials can impose some undesired effects on the consumers. In this regard, the standard safety measures should be designed and the necessary experiments of nanomaterials should be carried out. The various characteristics of nanomaterials such as physical, chemical, aggregation, porosity, morphology, size, solubility, and purity should be evaluated as per FDA guidelines. The studies regarding in vitro testing of non-cytotoxic concentrations of nanoparticles are reported for example, for AgNPs synthesized by using fenugreek leaves revealed the least cytotoxic effect against HaCaT cells at a concentration of 250 μg ml −1 [189]. AgNPs synthesized by using Albizia lebbeck flowers showed biocompatibility against the cell lines A549 revealed as the nanoparticles did not affect the viability of cell lines at a concentration range of 2 μg per ml to 50 μg per ml [190]. Iron oxide nanoparticles in the concentration of 0.1-10 μg per ml did not affect the cell lines (normal cell lines, glial cell lines and breast cancer cell lines ) revealing the biocompatible nature of nanoparticles [191]. A thorough study regarding safe doses of nanoparticles should be carried out so that the toxic effect of nanoparticles on the cells can be circumvented. The in vitro and in vivo toxicological studies of nanomaterials should be studied along with dermal penetration and potential inhalation, genotoxicity studies, and possible skin and eye irritation studies.
The route of exposure of nanomaterials is one of the vital facets to consider. The prime route of exposure to nanomaterials is skin specifically the stratum corneum. There are still some ambiguities with respect to the exposure of nanomaterials and penetration through the first layer of skin and this may lead the toxic effects. The nanomaterials which are used in cosmetic products should be subjected the further tests. The cosmetics which are in the form of sprays or aerosols should be taken more care of as these particles may enter through inhalation. The nanomaterials may show some changes in storage and handling. It can be more difficult to foretell the reactivities and risks associated with the products. The newly developed cosmetics should be tested for safety, efficiency, stability and aesthetics [192].
Due to the presence of significant properties of nanomaterials, the nanotechnology field has been growing to a greater extent as a large number of publications on this field can provide the evidence. However, research on nanoparticle toxicity needs to be considered. The risks associated with the use of nanomaterials need to be defined in different aspects. Strict implementations of different safety regulations are needed. Toxicity studies, the effect on human health and the environment of various nanomaterials used in the industry should be studied thoroughly.

Conclusions
Nanotechnology is a versatile field in which controlled synthesis of nanomaterials and their varied applications in different fields for different purposes can be achieved. In a current scenario, the main focus is upon the applications of nanomaterials for various purposes but the side effects or long-term effects of these nanomaterials on health should be taken into consideration. The toxic effects such as skin inflammation, skin cancer and genotoxicity may arise and they need to be thoroughly studied. The interactions between the nanomaterials and the skin have been derived through the experiments. Various types of nanoparticles have been used in cosmetic formulations. Nonetheless, further studies are needed to understand the toxic effects of nanomaterials as the side-effect-free character of cosmetic products is a significant aspect.

Data availability statement
All data that support the findings of this study are included within the article (and any supplementary files).