Spirulina for Skin Care: a Bright Blue Future

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Review Spirulina for Skin Care: A Bright Blue Future

Irene Ragusa, Giulia Nerina Nardone, Samuele Zanatta, Walter Bertin and Emanuele Amadio *

Labomar S.p.a., Via F. Filzi, 33, 31036 Treviso, Italy; [email protected] (I.R.); [email protected] (G.N.N.); [email protected] (S.Z.); [email protected] (W.B.) * Correspondence: [email protected]

Abstract: Spirulina stands out as a sustainable bioactive microalga with health-promoting properties, and an important active ingredient of natural cosmetics products. Currently, Spirulina has been incorporated in topical skin-care formulations, such as a moisturizing, antiwrinkles, antiaging and antiacne agent. Furthermore, this microalga is used by cosmetic formulators to promote healthy sunscreen protection, to treat skin pigmentation disorders and to heal wounds. Most of commercial cosmetics claim a large range of Spirulina properties, including antioxidant, revitalizing, remineralizing, moisturizing, protecting alongside cleansing and shining action, both for hair and for skin. In this review, recent cosmetic applications of Spirulina are revised, by highlighting its ability in improving skin appearance and health. Additionally, the analysis of the Spirulina cosmetic benchmark is discussed. Looking at the current emergence of the beauty industry, many Spirulina extracts and dry powder/flakes, both the starting ingredient and final Spirulina-based cosmetic products, are available on the market. In this industrial field, Spirulina—mainly Spirulina platensis and Spirulina maxima—is used either as a powder, like in the case of cheaper products, or as a phycocyanin-rich blue extract, particularly in the luxury market. It is likely that, in the coming years, diversity, quality and topical applications of Spirulina will rapidly increase.

Keywords: Spirulina; microalga; cyanobacteria; natural cosmetics; skin care; skin health

Citation: Ragusa, I.; Nardone, G.N.; Zanatta, S.; Bertin, W.; Amadio, E. Spirulina for Skin Care: A Bright 1. Introduction Blue Future. Cosmetics 2021, 8, 7. Since ancient times, botanical extracts have been extensively used in cosmetics and https://doi.org/10.3390/cosmetics skin care products. In recent decades, researchers have turned their interest towards 8010007 microalgae and cyanobacteria for the preparation of healthy and nutrient natural products,

Received: 20 October 2020 both as food and cosmetics [1,2]. Accepted: 14 December 2020 Between the microalgae, Spirulina (Arthrospira) is one of the most promising species, Published: 14 January 2021 due to its precious content of phytochemicals and its greener and more sustainable production chain. Spirulina is a unicellular cyanobacterial-type microalga, which grows at pH Publisher’s Note: MDPI stays neu- 10–12. The genus Athrospira includes a great variety of species (see, i.e., ref. [3]), such as the tral with regard to jurisdictional clai- most popular Spirulina platensis and Spirulina maxima. These two algae types differ in both ms in published maps and institutio- ultrastructural and morphological characteristics, alongside in their geographic origin: the nal afﬁliations. Spirulina platensis is mainly found in Africa and Asia, while Spirulina maxima is widespread in California and Mexico [4]. The safety of Spirulina utilization is well justiﬁed by its long history of use—this microalgae has been cultivated for centuries, and is still commonly consumed in Africa and in Chad—and by a plenty of in vivo/vitro studies [5–8]. Copyright: © 2021 by the authors. Li- Spirulina is considered also highly sustainable due to a multiplicity of synergic fac- censee MDPI, Basel, Switzerland. tors [1,9]: (i) it is easily grown in “bioreactors” under solar light with considerable savings This article is an open access article in water, soil and (ii) without the need of pesticide or herbicide. (iii) This pretty simple distributed under the terms and con- production process requires minimal operator training and technical supervision thus ditions of the Creative Commons At- tribution (CC BY) license (https:// ensuring a high economic impact. (iv) After cultivation the whole microalgae is used, creativecommons.org/licenses/by/ unlike other fruit and vegetable crops where root, stem and leaf systems are all byproducts, 4.0/). (v) helping to save energy, cutting greenhouse gas emissions and the overall environmental

Cosmetics 2021, 8, 7. https://doi.org/10.3390/cosmetics8010007 https://www.mdpi.com/journal/cosmetics Cosmetics 2021, 8, 7 2 of 19

impact. All these advantages are furthermore strengthened by the fact that (iv) Spirulina is highly dense and rich of nutrients and of phytochemicals [4,8–11]. Since the chemical composition of a given spirulina is strongly inﬂuenced by the genus and by the cultivation conditions, the list reported in Table1 have to be considered as an example.

Table 1. Phytochemicals of Spirulina [12].

Name Amount for 100 g of Raw Material Unit Water 90.67 g Calcium, Ca 12 mg Iron, Fe 2.79 mg Magnesium, Mg 19 mg Phosphorus, P 11 mg Potassium, K 127 mg Sodium, Na 98 mg Zinc, Zn 0.2 mg Copper, Cu 0.597 mg Manganese, Mn 0.186 mg Selenium, Se 0.7 µg Vitamin C, total ascorbic acid 0.9 mg Thiamin 0.222 mg Riboﬂavin 0.342 mg Niacin 1.196 mg Pantothenic acid 0.325 mg Vitamin B-6 0.034 mg Folate, total 9 µg Folate, food 9 µg Folate, DFE 9 µg Choline, total 6.5 mg Vitamin A, RAE 3 µg Carotene, beta 33 µg Vitamin A, IU 56 IU Vitamin E (alpha-Tocopherol) 0.49 mg Vitamin K (phylloquinone) 2.5 µg Fatty acids, total saturated 0.135 g 14:0 0.004 g 16:0 0.127 g 18:0 0.004 g Fatty acids, total monounsaturated 0.034 g 16:1 0.017 g 18:1 0.018 g Fatty acids, total polyunsaturated 0.106 g 18:2 0.064 g 18:3 0.042 g Tryptophan 0.096 g Threonine 0.306 g Isoleucine 0.331 g Leucine 0.509 g Lysine 0.312 g Methionine 0.118 g Cystine 0.068 g Phenylalanine 0.286 g Tyrosine 0.266 g Valine 0.362 g Arginine 0.427 g Histidine 0.112 g Alanine 0.465 g Aspartic acid 0.597 g Glutamic acid 0.864 g Glycine 0.319 g Proline 0.245 g Serine 0.309 g Cosmetics 2021, 8, 7 3 of 19

In general, the main components of spirulina are proteins, carbohydrates and lipids. Among the various proteins, the most relevant (total amount around 60% on a dry weight basis) are phycobiliproteins, namely phycocyanin, allophycocyanin, and phycoerythrin. Besides proteins, the other well represented category is that of fatty acids. The main lipids found in Spirulina are γ-linolenic acid (18:3, n-6) from omega-6 family and palmitic acid (16:0) both known for their pharmaceutical potential to prevent cardiovascular diseases, hypercholesterolaemia and other disorders. Furthermore, this alga is also a rich source of many other valuable compounds, such as several minerals and vitamins. The most commonly identified minerals are potassium, calcium, magnesium, selenium, iron and zinc. Among the vitamins, B vitamins are the most abundant. Its presence confers to the algae properties of in DNA repair, electron transfer, fatty acids synthesis and one-carbon metabolism [13]. Finally, in addition to phycobiliproteins mentioned before, other relevant Spirulina’s pigments are carotenoids and chlorophyll, whose colored compounds find potential interest in the food sector. Furthermore, these pigments exert potential health benefits over ingestion. There is evidence that the pigments consumption has enhanced the immune body response thus reducing the risk of developing degenerative chronic cardiovascular diseases, and certain types of cancer [14,15]. Nonetheless, Spirulina carries also out other pharmacological activities, i.e., enhancing body immunity against pathogenic bacteria, fungi, RNA viruses, including influenza and coronavirus [11,16–19] and preventing inflammatory diseases or cellular oxidative stress [20–22]. These features make this alga an attractive new ingredient, especially for the formulation of green and ecofriendly cosmetics [23]. In this context, a recent trend is using Spirulina food supplements as “nutricosmetics” that not only help to prevent diseases and become healthier, but also they enhance the natural beauty of skin, nails and hair [24–26]. However, despite the interest of the cosmetic-market in the natural-derived skin care products, up to now few studies have recommended the use of cyanobacteria for topic well-being treatments. In connection to the wide-ranging interests of our company in developing sustainable and innovative extracts [27,28] and high-quality food supplements, medical devices, foods for special medical purposes, probiotics and cosmetics [29]; in this paper we brieﬂy review recent publications about cosmetic applications of Spirulina, with a focus on its potential activities and uses for improving appearance and skin health.

2. Benefits of Spirulina for Skin Care Formulations To date, few research have aimed at studying and demonstrating the Spirulina’s healthy effect on the skin. The most of cosmetic actions, supported by the literature and claimed by the market, are firstly the antiage one, including moisturizing, antioxidant and brightening proprieties, and secondly the antiacne and wound healing properties. The most relevant articles about this topic, which were published during the last few years, are Cosmetics 2021, 8, x FOR PEER REVIEW 4 of 20 classified in Figure1, Table2 and in the hereafter discussion.

Figure 1. Current 1. Current application application of Spirulina in of skinSpirulina care. in skin care. Table 2. Selection of recent studies about the skin care benefits of Spirulina herein discussed.

Topic Study Object Outcome of the Study Year Reference Spirulina in dermocosmetic Benefits on hydration, skin barrier function and oil con- 2015 [30] formulations trol. Antiaging effects. The enzymatic fermentation increased the efficiency of Spirulina fermented extracts Antiage— spirulina in inducing skin hydration and osmotic pro- 2018 [31] for skin care applications Moisturizing tecting activities Stimulation of fibroblast proliferation and on the gly- Dermatological effect of pep- 2018; cosaminoglycans and collagen’s synthesis; anti-aging [10,32] tide extract of Spirulina 2006 benefits Sunscreen formula with algae Synergistic effect of the contemporary use of UV-filters 2012 [33] as active ingredients and Spirulina; increase skin protection and appearance Antiage— Benefits on health of the dermis and the skin elasticity, Antioxidant Spirulina as antioxidant for reduction of skin hyperpigmentation, protection 2017 [34] sunscreen formulation against photoaging and inhibition of ROS-induced damage to the dermis. C-phycocyanin dose-dependent decrease of tyrosinase Antimelanogenic effect of c- activity and melanin content. Best result with 0.1 2011 [35] Antiage— phycocyanin from Spirulina mg/mL of Cpc. Brightening Spirulina for skin whitening Great potential to treat pigmentary disorders. High ac- 2018 [36] cosmetics tivity toward tyrosinase inhibition Significant improvement in the wound healing activity. In vivo wound healing activity Best result with ointment containing 10 % w/w of petro- 2011 [37] of spirulina extracts leum ether extract In vivo and in vitro wound Promising wound healing activity of crude Spirulina ex- healing effect of crude Spir- tract. Activity related to the presence of a mixture of 2013 [38] ulina extract and phycocyanin phycocyanin and carotenoids. Wound healing and antioxi- Cell proliferation, migration and immunoactivity were Wound heal- dant activities of Spirulina ex- increased by incorporation of crude algae extracts in the 2017 [39] ing tract incorporated in skin formulation. Spirulina had no genotoxic effect on hu- cream man peripheral blood cells.

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Table 2. Selection of recent studies about the skin care beneﬁts of Spirulina herein discussed.

Topic Study Object Outcome of the Study Year Reference Spirulina in dermocosmetic Benefits on hydration, skin barrier function and 2015 [30] formulations oil control. Antiaging effects. Antiage— The enzymatic fermentation increased the Spirulina fermented extracts for Moisturizing efficiency of spirulina in inducing skin 2018 [31] skin care applications hydration and osmotic protecting activities Stimulation of fibroblast proliferation and on Dermatological effect of the glycosaminoglycans and collagen’s 2018; 2006 [10,32] peptide extract of Spirulina synthesis; anti-aging benefits Synergistic effect of the contemporary use of Sunscreen formula with algae UV-filters and Spirulina; increase skin 2012 [33] as active ingredients Antiage— protection and appearance Antioxidant Benefits on health of the dermis and the skin Spirulina as antioxidant for elasticity, reduction of skin hyperpigmentation, 2017 [34] sunscreen formulation protection against photoaging and inhibition of ROS-induced damage to the dermis. C-phycocyanin dose-dependent decrease of Antimelanogenic effect of tyrosinase activity and melanin content. Best 2011 [35] Antiage— c-phycocyanin from Spirulina result with 0.1 mg/mL of Cpc. Brightening Spirulina for skin whitening Great potential to treat pigmentary disorders. 2018 [36] cosmetics High activity toward tyrosinase inhibition Significant improvement in the wound healing In vivo wound healing activity activity. Best result with ointment containing 2011 [37] of spirulina extracts 10 % w/w of petroleum ether extract In vivo and in vitro wound Promising wound healing activity of crude healing effect of crude Spirulina extract. Activity related to the presence of 2013 [38] Spirulina extract and a mixture of phycocyanin and carotenoids. phycocyanin Wound Cell proliferation, migration and Wound healing and healing immunoactivity were increased by antioxidant activities of incorporation of crude algae extracts in the 2017 [39] Spirulina extract incorporated formulation. Spirulina had no genotoxic effect in skin cream on human peripheral blood cells. PCL-nanofibers containing Spirulina extract were Spirulina- polycaprolactone demonstrated to be effective on dermal wound (PCL) nanofiber wound healing in a rat model. Additional Alginate dressing to 2016, 2017 [40,41] impregnation increased the adhesiveness and improve cutaneous wound moisture of the skin and expedited wound healing healing without causing cytotoxicity. Formulation and Development Topical application of phycocyanin rich ointment of Topical Antiacne successfully employed in the treatment of acne 2018 [42] Formulation of Spirulina against P.acne and S. epidermidis. extract Antiacne The face mask was able to inhibit Cutibacterium In vitro evaluation of face acnes with a diameter of inhibition zone was 10 mask containing extract and ± 0.4 mm. The antibacterial activity was due to 2019 [43] biomass of Spirulina platensis the presence of alkaloids, steroids, saponins and its antibacterial activity and phenol in S. platensis extract. Cosmetics 2021, 8, 7 5 of 19

2.1. Antiage 2.1.1. Moisturizing Skin aging is a complex process that depends on both a genetic predisposition and external factors, and causes functional and structural skin damage. Water molecules play a pivotal role in maintaining the skin structural proprieties: indeed, water binds the dermal proteins, such as collagen, and ensures the tissue thickness. Therefore, aged skin is poor of bounded water and has weak hydration networks, which make skin look less and less glowy and firm. Typically, UV radiation, pollution, a poor diet and an unhealthy lifestyle are the main causes of skin aging, and therefore of the loss of moisture together with the decrease of skin barrier. Currently, the increase in life expectancy and the growing interest in a youthful appearance have led the cosmetic market to formulate antiage products with moisturizing and wrinkle reduction effects. Considering that beauty companies are also involved in searching sustainable raw materials and active ingredients, the studies on the antiaging effects of algae, like Spirulina, aroused great interest in recent years [44,45]. In this context, Delsin et al., in 2015 firstly promoted the use of Spirulina as an innovative ingredient for dermocosmetic products. They showed how the microalga improves the epidermis structure and acts as a hydration booster with positive results on skin barrier function, particularly to skin protection and antiage, and oil control [30]. Delsin’s research team prepared a gel-cream, formulated with the following ingredients: fatty alcohols, ammonium acryloyldimethyltaurate, NP copolymer and methylphenyl polysiloxane, phe- noxyethanol and parabens, BHT and distilled and deionized water. This formulation was on the one hand supplemented gel cream containing 0.1% (w/w) of dry extract of Spirulina (FGA) and, on the other hand, it was gel cream free from the active alga(vehicle—FGV). They were both applied twice daily on the participants face area. In particular, 40 female healthy participants, aged between 18 and 39 (young group) and 40 and 65 (mature group), with phototypes II, III or IV, took part in the clinical study. Both groups were divided into two subgroups, composed of ten people each: the first group used the formulation containing Spirulina extract while the second one used the vehicle gel-cream. For comparison data were collected before or after the application of the cream (in total 28 days). The parameters considered were: skin hydration, trans epidermal water loss (TEWL), skin microrelief, sebum content (on the forehead region), dermis echogenicity and morphological and structural epidermal features (in the periorbital region), before and after the aforementioned trial period. Among these parameters, trans epidermal water loss is the most important for revealing the skin barrier quality and, consequently, the skin moisture content. The results showed a significant increase of the stratum corneum water content,

Cosmetics 2021, 8, x FOR PEER REVIEWa reduction of TEWL (Figure2) and the amount of sebum on the skin6 (Figure of 20 3), and an enhancement of the echogenicity of the dermis and the distribution of keratinocytes.

FigureFigure 2. 2. TransepidermalTransepidermal water water loss before loss (t0), before and (t0),after and28 days after (t28) 28 of daysapplication (t28) of the application formu- of the formulations FGA (gel cream containing 0.1% of Spirulina extract) and FGV (gel cream without Spirulina lationsextract) FGAin young (gel skin cream (18–39 containing years) (A) and 0.1% mature of Spirulina skin (40–65extract) years) (B and). (* Kruskal–Wallis, FGV (gel cream p < without Spirulina extract)0.05). Published in young by ref. skin [30]. (18–39 years) (A) and mature skin (40–65 years) (B). (* Kruskal–Wallis, p < 0.05). Published by ref. [30].

Figure 3. Sebum content of the skin before (t0), and after 28 days (t28) of application of the formulations FGA (gel cream containing 0.1% of Spirulina extract) and FGV (gel cream without Spirulina extract) on young skin (18–39 years) (A) and mature skin (40–65 years) (B) (* Kruskal–Wallis, p < 0.05). Published by ref. [30].

As result of this study, the Spirulina’s fatty acids, such as α and γ linolenic acid, in- hibited isoenzyme type 1 metabolism and improved the oily skin appearance. The poly- saccharides contained in the alga extract, instead, stimulate the cell division process and contribute to the keratinization processes or to renew the stratum corneum. Vitamins, minerals and proteins contained into the alga may further contribute in improving skin microrelief and hydration. Therefore, Spirulina extract was essential to improve the hydrolipidic character, regenerate the skin tissue thus protecting and moisturizing the skin. These effects were greatly visible on the mature group. To further investigate the behaviors of the spirulina in the skin care, in 2018 F. Apone et al. tested and compared two Spirulina with the analogous unfermented. The reported data show a greater effectiveness of the enzymatically fermented extract in moisturizing and protecting the skin cells [31]. Another important aspect related to skin aging is the peptides reduction in the dermis extracellular matrix. Peptides are a short chain of amino acidic residues, which are involved in several physiological processes, such as inflammation, immune response and skin remodeling, and stimulate the synthesis of structural proteins (collagen and elastin). For this reason, cosmetic products that are rich in peptides may prevent the onset of wrinkles and signs of aging [46]. As most cyanobacteria, Spirulina contains several bioactive compounds, notably proteins (53–62%). A large number of peptides have been screened, fractionated and purified from Spirulina extracts and further used into pharmaceuticals

Cosmetics 2021, 8, x FOR PEER REVIEW 6 of 20

Figure 2. Transepidermal water loss before (t0), and after 28 days (t28) of application of the formu- Cosmetics 2021, 8, 7 lations FGA (gel cream containing 0.1% of Spirulina extract) and FGV (gel cream without Spirulina6 of 19 extract) in young skin (18–39 years) (A) and mature skin (40–65 years) (B). (* Kruskal–Wallis, p < 0.05). Published by ref. [30].

FigureFigure 3. 3.Sebum Sebum content content of of thethe skinskin beforebefore (t0),(t0), andand afterafter 2828 daysdays (t28)(t28) ofof applicationapplication of the formu- lationslations FGA FGA (gel (gel cream cream containing containing 0.1% 0.1% of ofSpirulina Spirulinaextract) extract) andand FGVFGV (gel(gel creamcream withoutwithout SpirulinaSpirulina extract)extract) on on young young skin skin (18–39 (18–39 years) years) (A ()A and) and mature mature skin skin (40–65 (40–65 years) years) (B) ( (*B Kruskal–Wallis,) (* Kruskal–Wallis,p < 0.05).p < 0.05). Published by ref. [30]. Published by ref. [30].

AsAs resultresult ofof thisthis study, the Spirulina’s’s fatty fatty acids, acids, such such as as α αandand γ γlinoleniclinolenic acid, acid, in- inhibitedhibited isoenzyme isoenzyme type type 1 metabolism 1 metabolism and and im improvedproved the theoily oily skin skin appearance. appearance. The poly- The polysaccharidessaccharides contained contained in the in thealga alga extract, extract, inst instead,ead, stimulate stimulate the thecell celldivision division process process and andcontribute contribute to the to the keratinization keratinization processes processes or or to to renew renew the the stratum corneum.corneum. Vitamins,Vitamins, mineralsminerals and and proteins proteins contained contained into into the the alga alga may may further further contribute contribute in in improving improving skin skin microreliefmicrorelief and and hydration. hydration. Therefore,Therefore,Spirulina Spirulinaextract extract was was essential essential to improveto improve the the hydrolipidic hydrolipidic character, character, regen- re- erategenerate the skin the tissueskin tissue thus protectingthus protecting and moisturizing and moisturizing the skin. the These skin. effects These were effects greatly were visiblegreatly on visible the mature on the group.mature To group. further To investigatefurther investigate the behaviors the behaviors of the spirulina of the spirulina in the skinin the care, skin in care, 2018 in F. Apone2018 F. etAp al.one tested et al. and tested compared and compared two Spirulina two Spirulinawith the with analogous the analo- un- fermented.gous unfermented. The reported The datareported show data a greater show effectiveness a greater effectiveness of the enzymatically of the enzymatically fermented extractfermented in moisturizing extract in moisturizing and protecting and the protecting skin cells the [31 skin]. cells [31]. AnotherAnother important important aspect aspect related related to to skin skin aging aging is theis the peptides peptides reduction reduction in the in dermisthe der- extracellularmis extracellular matrix. matrix. Peptides Peptides are a short are chaina short of chain amino of acidic amino residues, acidic whichresidues, are which involved are ininvolved several physiologicalin several physiological processes, processes, such as inflammation, such as inflammation, immune responseimmune response and skin and remodeling,skin remodeling, and stimulate and stimulate the synthesis the synthesis of structural of structural proteins (collagenproteins (collagen and elastin). and For elastin). this reason,For this cosmetic reason, cosmetic products products that are rich that in are peptides rich in peptides may prevent may theprevent onset the of wrinklesonset of wrin- and signskles ofand aging signs [46 of]. aging As most [46]. cyanobacteria, As most cyanobacteria,Spirulina contains Spirulina several contains bioactive several compounds, bioactive notablycompounds, proteins notably (53–62%). proteins A large (53–62%). number A large of peptides number have of peptides been screened, have been fractionated screened, andfractionated purified fromand purifiedSpirulina fromextracts Spirulina and further extracts used and into further pharmaceuticals used into pharmaceuticals and cosmetic applications. With this purpose, in 2006 a French research team patented a dermatological peptide extract of Spirulina, claiming positive effects on the stimulation of fibroblast proliferation and on the glycosaminoglycans and collagen’s synthesis [32]. Moreover, a few years later, also Wang Z. et al., presented a study about antiaging peptides extracted from Spirulina platensis at the 13th International Congress on amino acids, peptides and proteins in Vienna [10].

2.1.2. Antioxidant The antioxidant potential of blue-colored cyanobacteria is of great interest in the cosmesis. Pigments can be used as natural colorants in make-up products, like eyeliner and lipstick, and as antioxidant agents, which protect against UV radiation [1,23]. Indeed, Spirulina contains a lot of photosynthetic pigments like chlorophyll and especially phycocyanin, which determine a long-lasting green-blue coloration in cosmetic formulas (Figure4) [47]. In 2012 Dr. Lotan A. (Nidaria Technology Ltd., Israel) patented some biologic sunscreen formulas, which included a blend of algae as active ingredients [33]. The claimed activity was the synergistic effect of the simultaneous use of UV ﬁlters and algae, which absorb sunlight, “convert it in energy source”, protect the skin and improve its appearance. The patent argues that “the agent primarily responsible for the improved effect on the Cosmetics 2021, 8, x FOR PEER REVIEW 7 of 20

and cosmetic applications. With this purpose, in 2006 a French research team patented a dermatological peptide extract of Spirulina, claiming positive effects on the stimulation of fibroblast proliferation and on the glycosaminoglycans and collagen’s synthesis [32]. Moreover, a few years later, also Wang Z. et al., presented a study about antiaging peptides extracted from Spirulina platensis at the 13th International Congress on amino acids, peptides and proteins in Vienna [10]. Cosmetics 2021, 8, 7 7 of 19

2.1.2. Antioxidant The antioxidant potential of blue-colored cyanobacteria is of great interest in the cos- skinmesis. is thePigments incorporation can be used of the as algae” natural and colorantsSpirulina inwas make-up one of products, the tested like algae eyeliner (Spirulina and, Dunalielalipstick, and, Hematococus as antioxidant, Nannochlorosis agents, whichand protectTetraselmis against). However, UV radiation despite [1,23]. the Indeed, importance Spir- ofulina this contains statement, a lot an of undeniable photosynthetic scientiﬁc pigments demonstration like chlorophyll is missing. and Theespecially patent phycocya- proposed threenin, which formulations determine containing a long-lasting 10% green-bluew/w non-viable coloration intact in algae, cosmetic a topical formulas gel (Figure and both 4) W/O[47]. and O/W emulsions.

(a) (b)

Figure 4. TwoTwo formulas formulas made made by by AromataGroup: AromataGroup: (a ()a Mermaid) Mermaid Instant Instant Mask Mask with with spirulina spirulina and and rameic chlorophyll and (b) Marble Lipbalm with spirulina extract. Published by ref. [47]. rameic chlorophyll and (b) Marble Lipbalm with spirulina extract. Published by ref. [47].

FewIn 2012 years Dr. later, Lotan C. A. Souza (Nidaria et al., Technology further developed Ltd., Israel) a stable patented and effectivesome biologic sunscreen sun- formulationscreen formulas, containing which aincluded mixture a of blend UV filters of algae and as antioxidants active ingredients (using Spirulina [33]. Thebetween claimed theactivity others). was the As suchsynergistic it further effect encourages of the simu researchersltaneous use to of design UV filters more and efficacious algae, which and reliableabsorb sunlight, sunscreens “convert (Table3 it)[ in34 energy]. As an source”, antioxidant, protectSpirulina the skinmay and reduce improve skin its hyperpig- appear- mentationance. The patent and protect argues skin that against “the agent sun-induced primarily damages responsible (e.g., for photoaging) the improved by inhibiting effect on ROS-inducedthe skin is the damageincorporation to the of dermis. the algae” Both and visual Spirulina and rheological was one of analyses the tested revealed algae (Spir- that theulina sunscreen, Dunaliela formulations, Hematococus were, Nannochlorosis stable during and the Tetraselmis study period.). However, Therefore, despite the inclusion the im- ofportance UV filters of this Tinosorb statement,® S, Tinosorban undeniable® M, Uvinul scientific® APlus demonstration and Uvinul is missing.® T150, alongThe patent with Spirulinaproposeddry three extract formulations and dimethylmethoxy containing 10% chromanol-loadedw/w non-viable intact solid algae, lipid a topical nanoparticles gel and (DMC-loadedboth W/O and SLN)O/W emulsions. did not alter the physical stability of the cream. Such formulations wereFew characterized years later, by C. a Souza pH range et al., between further 5.3developed and 5.8, a suitable stable and for topicaleffective application. sunscreen DMC-loadedformulation containing SLN were a successfully mixture of UV produced filters and with antioxidants a high inclusion (using rate Spirulina (approximately between 96%,the others). after 24 As h) such andstability it further (54 encourages days). These researchers formulations to design exhibited more a non-Newtonianefficacious and andreli- pseudoplasticable sunscreens behavior (Table 3) and, [34]. in As terms an antioxidant, of safety, according Spirulina may to the reduce sensorial skin analyses,hyperpigmen- they didtation not and irritate protect the skin.skin against sun-induced damages (e.g., photoaging) by inhibiting ROS-induced damage to the dermis. Both visual and rheological analyses revealed that Table 3. Compositionthe of sunscreen the sunscreen formulations cream based were on UV stable filters during and antioxidants. the studyPublished period. Therefore, by Ref. [34 ].the inclusion ® ® ® ® of UV filters Tinosorb S, Tinosorb M, Uvinul APlusConcentration and Uvinul (% T150,w/w) along with Spir- ulina dry extract and dimethylmethoxy chromanol-loaded solid lipid nanoparticles Composition a Formulation Codes (DMC-loaded SLN) did not alter the physical stability of the cream. Such formulations were characterized by a pH range betweenF1 5.3 and 5.8, suitable F2 for topical application. F3 OilDMC-loaded phase b SLN were successfully produced12.6 with a high inclusion 12.6 rate (approximately 12.6 Preservative96%, after 24 h) and stability (54 days). These 0.8 formulations 0.8 exhibited a non-Newtonian 0.8 Aqueousand phasepseudoplastic behavior and, in terms 3.1 of safety, according 3.1 to the sensorial 3.1 analyses, ® Bis-ethylhexyl methoxyphenylthey did triazine—Tinosorb not irritate the skin.S - 4.0 4.0 Diethylamino hydroxybenzoyl hexyl benzoate—Uvinul® APlus - 1.0 1.0 Ethylhexyl triazone—Uvinul® T150 - 4.0 4.0 Methylene bis-benzotriazolyl tetramethylbutylphenol—Tinosorb® M - 6.0 6.0 Spirulina dry extract - - 0.1 DMC-loaded SLN c - - 10.0 Water solvent q.s. 100 g 100 g 100 g a Qualitative composition was reported in accordance with INCI (International Nomenclature of Cosmetic Ingredient). b Quantitative composition of oil and aqueous phases were previously reported by ref. [48]. c DMC final concentration into F3 formulation was 0.05% (w/w). DMC-loaded SLN: dimethylmethoxy chromanol-loaded solid lipid nanoparticles. Cosmetics 2021, 8, 7 8 of 19

The C. Souza’s research team examined the photoprotective effects of the developed formulations, both in vitro and in vivo, and highlighted the pivotal contribution of the addition of Spirulina. The in vitro UVA protection of formula F2 and F3 was evaluated by the UVA/UVB ratio and by the critical wavelength. The in vivo SPF values of both formulations were nearly 30 while the in vitro SPF values of formulations F2 and F3 were respectively around 2.5-times and 3.0-times higher than those obtained in vivo. Therefore, in vitro results suggest that the combination of Spirulina and SLN loaded DMC with UV filters improve the SPF value. However, in vivo tests did not adequately confirm this result. It has been observed that, while in vitro experiment measures the formulation trans- mittance, the in vivo procedure determines the effective ability to prevent inflammatory reaction (erythema) triggered by solar radiation. This means that Spirulina increase the light scattering properties without furnishing enough anti-inflammatory activity. To further clarify the benefit of using Spirulina into the formulations, a 3-month single-blind clinical study has been carried out with 44 healthy participants (30–50 years old), during which the water content of stratum corneum, TEWL, dermis echogenicity and skin elasticity and pigmentation were measured. The results showed that Spirulina- supplemented sunscreen significantly improves both the health of the dermis and the skin elasticity after 84 days of the treatment, with respect to the sunscreen itself. Moreover, as previously stated by Delsin et al. [30], topically applied Spirulina regenerates the skin barrier and reduces the loss of water.

2.1.3. Brightening Skin hyperpigmentation is an aesthetic issue, which raises a growing concern in the current cosmetic market. Currently, whitening products are pivotal in the antiage skin care routine, since they reduce spots and skin dyschromia caused by UV exposure. The pigmentogenesis begins inside melanocytes, which are a type of cell located between the keratinocytes in the basal layer of epidermis. During the mentioned process, tyrosinase plays an important role in controlling the production of melanin and then in coloring hair, skin and eyes. In fact, this multicopper enzyme facilitates the transformation of L-tyrosine in L-dihydroxyphenylalanine (L-DOPA), which in turn oxidizes itself and becomes DOPA- quinone. A set of spontaneous cascade reactions leads to the creation of a pigment polymer, called melanin, which is released to the surrounding keratinocytes [49]. Both the abnormal loss and the overproduction of melanin may generate serious esthetical and dermatological skin disorders in humans, such as Acanthosis nigricans, melasma, Cervical poikiloderma, Lentigines, Periorbital hyperpigmentation, neurodegeneration associated with skin cancer risk and Parkinson’s disease. The most reliable strategy to treat such pigmentary disorders so far is to use inhibitors of the tyrosinase. In the last decades, a huge number of natural and artiﬁcial inhibitors have been suggested for the production of hypopigmentation pharmaceuticals, antibrowning agents and skin whitening cosmetics [36,50–53] (Table4). Arbutin, kojic acid and hydroquinone are among the best-known inhibitors, even though their use is currently limited because of certain side effects, among which irritation and allergies. Indeed, hydroquinone in cosmetic products is also forbidden by the EU and the FDA [54]. As a result, the use of Spirulina as a safer and greener tyrosinase inhibitor might have a huge potential application in the ﬁeld. The effect of Spirulina on skin pigmentation was examined in detail by S. Sahin et al., in 2018 [36]. They demonstrated that this microalga has a big potential for the inhibition of tyrosinase and might be used for the development of skin whitening cosmetics, totally effective and safe. S. Sahin showed a high inhibitory effect on mushroom tyrosinase activity of Spirulina’s extracts. Moreover, the tyrosinase activity remarkably reduced in a dose dependent manner. In particular, the IC50 values of tyrosinase inhibition with Spirulina water and ethanol extracts were found as 1.4 × 10−3 and 7.2 × 10−3 g/mL, respectively. The values just mentioned were compared with other known natural tyrosinase inhibitors, and were found to be bigger than the IC50 value of kojic acid (IC50 = 2.8 × 10−4 g/mL). Cosmetics 2021, 8, 7 9 of 19

Overall, the whitening activity of Spirulina may be related to the presence of a phytocomplex containing vanillic acid—as the main phenolic acid component—caffeic acid and ferulic acid, which all synergically act to inhibit the enzyme. Another important component that could be responsible for this antimelanogenic effect is the c-phycocyanin, which has also antioxidant properties, as mentioned above. In fact, in 2011 a research team from Taiwan studied how this protein modulates the tyrosinase expression, both in transcriptional and post-transcriptional levels [35]. The outcomes of the study show that C-phycocyanin inhibits the pathway of p38 mitogen-activated protein (MAP) kinases, by downregulating the CREB activation and then the melanocyte inducing transcription factor (MITF) expression. At the same time, C-phycocyanin fits in the physiologic retro- control mechanism, that is a post-transcriptional pathway that downregulates an over synthesis of melanin. In doing so, the influence of the blue protein increases the cAMP levels (Figure5) that trigger the MAPK/ERK pathway, which in turn phosphorylates the MITF on Serine 73. This last step results in an increased transcriptional activity and, at the same time, in the protein binding with ubiquitin monomers, which ends with the degradation of the transcription factor. Li-Chen Wu and his team studied the concentrations needed to suppress the tyrosinase activity and the following melanin content as well. As shown in Figure6, the enzyme activity decreased in line with the pigment concentration, according to a C-phycocyanin dose-dependent trend. In particular, the enzyme activity was reduced from 75.7% to 65.7% and the pigment concentration from 56.2% to 47.5%, using a C-phycocyanin treatment with a range from 0.05 to 0.1 mg/mL. The higher concentration (0.2 mg/mL) was excluded from the study results because it affected the viability of B16F10 melanoma cells, even though it contributed to a great decrease in both tyrosinase activity and melanin content.

Table 4. Natural blends with inhibitory activity of tyrosinase. Published by Ref. [36] and references therein.

Compounds IC50 Substrate Ethanol extract of Cudrania tricuspidata twig 1.14 × 10−4 g/mL L-tyrosine Steppogenin from C. tricuspidata 2.52 ± 0.66 µM/7.26 × 10−7 g/mL L-tyrosine Oxyresveratrol from C. tricuspidata 2.85 ± 0.26 µM/6.96 × 10−7 g/mL L-tyrosine Trans-dihydromorin from C. tricuspidata 21.54 ± 0.84 µM/6.55 × 10−6 g/mL L-tyrosine Quercetin from C. tricuspidata 54.58 ± 0.89 µM/1.65 × 10−5 g/mL L-tyrosine Dihydrokaempferol from C. tricuspidata N100 µM/N2.88 × 10−5 g/mL L-tyrosine Protocatechuic acid from C. tricuspidata N500 µM/N7.71 × 10−5 g/mL L-tyrosine Naringenin from C. tricuspidata N500 µM/N1.36 × 10−4 g/mL L-tyrosine Kojic acid (standard tyrosinase inhibitor) 50.43 ± 1.75 µM/7.17 × 10−6 g/mL L-tyrosine Kojic acid (standard tyrosinase inhibitor) 0.67 mM/9.52 × 10−5 g/mL L-DOPA 85% ethanol extract of Hesperethusa crenulata bark 8.6 × 10−4 g/mL L-tyrosine Water extract of H. crenulata bark 1.09 × 10−3 g/mL L-tyrosine Methanol extract of H. crenulata bark 1.42 × 10−3 g/mL L-tyrosine Methanol extract of Magnolia denudata 3.34 × 10−3 g/mL L-tyrosine Methanol extract of M. denudata var. purpurascens 1.06 × 10−2 g/mL L-tyrosine 50% methanol extract of Podocarpus elongatus leaves and stem 4.7 × 10−4 and 1.4 × 10−4 g/mL, respectively L-DOPA 50% methanol extract of P. falcatus leaves and stem 2.9 × 10−4 and 3.5 × 10−4 g/mL, respectively L-DOPA 50% methanol extract of P. henkelii leaves and stem 3.7 × 10−4 and 0.4 × 10−4 g/mL, respectively L-DOPA 50% methanol extract of P. latifolius leaves and stem 4.1 × 10−4 and 3.6 × 10−4 g/mL, respectively L-DOPA Dieckol from Ecklonia cava 20 µM/1.49 × 10−5 g/mL L-tyrosine Cinnamic acid 2.10 mM/3.11 × 10−4 g/mL L-DOPA Ferulic acid 0.559 mM/1.09 × 10−4 g/mL L-tyrosine Caffeic acid 0.037 mM/6.67 × 10−5 g/mL L-tyrosine Ethanol and water extract of A. platensis 1.4 × 10−3 and 7.2 × 10−3 g/mL, respectively L-DOPA Cosmetics 2021, 8, x FOR PEER REVIEW 10 of 20

Cosmetics 2021, 8, x FOR PEER REVIEW 10 of 20

downregulating the CREB activation and then the melanocyte inducing transcription factor (MITF) expression. At the same time, C-phycocyanin fits in the physiologic retro-con- troldownregulating mechanism, thethat CREB is a post-transcription activation and thenal pathwaythe melanocyte that downregulates inducing transcription an over syn- fac- thesistor (MITF) of melanin. expression. In doing At the so, same the influence time, C-ph of ycocyaninthe blue protein fits in increasesthe physiologic the cAMP retro-con- levels (Figuretrol mechanism, 5) that trigger that isthe a post-transcriptionMAPK/ERK pathwaal pathwayy, which inthat turn downregulates phosphorylates an theover MITF syn- onthesis Serine of melanin. 73. This lastIn doing step results so, the ininfluence an increased of the transcriptional blue protein increases activity and,the cAMP at the levelssame time,(Figure in 5)the that protein trigger binding the MAPK/ERK with ubiquitin pathwa monomers,y, which whichin turn ends phosphorylates with the degradation the MITF ofon the Serine transcription 73. This last factor. step resultsLi-Chen in Wu an incrandeased his team transcriptional studied the activity concentrations and, at the needed same totime, suppress in the theprotein tyrosinase binding activity with ubiquitin and the followingmonomers, melanin which contentends with as thewell. degradation As shown inof Figurethe transcription 6, the enzyme factor. activity Li-Chen decreased Wu and in linehis teamwith thestudied pigment the concentrationsconcentration, accord-needed ingto suppress to a C-phycocyanin the tyrosinase dose-dependent activity and the trend. following In particular, melanin the content enzyme as activitywell. As was shown re- ducedin Figure from 6, the75.7% enzyme to 65.7% activity and decreasedthe pigment in lineconcentration with the pigment from 56.2 concentration,% to 47.5%, usingaccord- a Cosmetics 2021, 8, 7 C-phycocyanining to a C-phycocyanin treatment dose-dependent with a range from trend. 0.05 In to particular, 0.1 mg/mL. the The enzyme higher activity concentration was re- 10 of 19 (0.2duced mg/mL) from 75.7% was excludedto 65.7% andfrom the the pigment study resultsconcentration because from it affected 56.2% to the 47.5%, viability using of a B16F10C-phycocyanin melanoma treatment cells, even with though a range it fromcontribu 0.05ted to to0.1 a mg/mL. great decrease The higher in both concentration tyrosinase activity(0.2 mg/mL) and melanin was excluded content. from the study results because it affected the viability of B16F10 melanoma cells, even though it contributed to a great decrease in both tyrosinase activity and melanin content.

Figure 5. Effect of C-phycocyanin (Cpc) on B16F10 murine melanoma cell viability. The asterisk (*) Figureindicates 5. a Effectsignificant of difference C-phycocyanin from control (Cpc) group on(*, pB16F10 < 0.05). Published murine by melanoma Ref. [35]. cell viability. The asterisk (*) indicatesFigure 5. Effect a signiﬁcant of C-phycocyanin difference (Cpc) on from B16F10 control murine groupmelanoma (*, cellp < viability. 0.05). The Published asterisk (*) by Ref. [35]. indicates a significant difference from control group (*, p < 0.05). Published by Ref. [35].

Figure 6. Effect of C-phycocyanin (Cpc) on tyrosinase activity (black) and melanin content (grey). The asterisk (*) has been used to denote a significant difference from control group (*, p < 0.05; **, p

0.05) at the range of doses (33.5–0.0335 µg/mL) examined. It was also discovered that 1.25% of C-phycocyanin has a superior effect on the in vivo efﬁciency, compared to other preparations with Spirulina extract, on the 7th day. Overall, the proliferation and growth stimulation activities of Spirulina extract seem to be directly connected to the presence of both phycocyanin and carotenoids, which synergistically Cosmetics 2021, 8, 7 11 of 19

contribute to the wound healing and tissue regeneration. A few years later, Gunes et al. developed natural skin creams enriched with bioactive S. platensis extract, and studied its wound healing, genotoxic and immunoreactive effects in vitro to evaluate the potential use of Spirulina in biomedical and pharmaceutical sector [39]. The in vitro cell culture tests demonstrated that Spirulina extracts showed significant effects on fibroblast cell proliferation and migration. Fibroblasts are mesenchymal cells that enable tissue preservation by secreting extracellular matrix, and they are in charge of the inflammation and scar formation, during the wound healing process. A skin-care cream, which incorporates 1.125% of Spirulina extract, presented the biggest proliferative effect on skin cells with an increase of Type 1 collagen immunoreactivity. The micronucleus assay, which shows DNA damage, demonstrated that Spirulina based cream had no genotoxic effect on human peripheral blood cells. Additionally, Spirulina platensis also revealed a strong antioxidant property, due to its superoxide dismutase (SOD) activity with values up to 8.0 U/mL of SOD in Spirulina extract. All these features lead the blue-green microalga to be suitable for biomedical and cosmetic applications, particularly for wound dressings as well as sunburns, erythema and photoaging. More recently a Korean research team absorbed Spirulina in an engineered-tissue, to evaluate its wound healing potential [40,41]. They selected nanofibers of polycaprolactone (PCL) as a supporting material suitable for tissue regeneration. PCL, which is an FDA-approved polymer, is also biocompatible, biodegradable and known to favor the oxygen absorptivity, the drainage capability and the water evaporative control, which are critical factors for the skin regeneration. In a study, Spirulina aqueous extract was absorbed on the nanomaterial and the wound regeneration was evaluated using an in vivo wound model [40]. In this specific regard and from a bioethical view, we contest such use of an animal for analysis in the cosmetic field and we strongly recommend the stakeholders to find other cruelty free alternatives to perform efficiency tests. In general, Spirulina-PCL helped to regenerate wounds and enhanced skin regeneration, by improving the antioxidant mechanism against the reactive oxygen species (ROS) of fibroblast under oxidative

Cosmetics 2021, 8, x FOR PEER REVIEWstress (Figure7). Nevertheless, the developed nanoﬁbers had a restricted12 of 20 capability to moisturize wounded skin because of the hydrophobicity of PCL.

Figure 7. Schematic design of the Spirulina-PCL nanofibers application to cutaneous wound. Pub- Figurelished by 7. Ref.Schematic [40]. design of the Spirulina-PCL nanoﬁbers application to cutaneous wound. Pub- lished by Ref. [40]. To resolve the issue of the hydrophobic behavior of Spirulina-PCL nanofibers, the alginateTo was resolve addedthe in a issuefollowing of step the due hydrophobic to its high hydrophilicity behavior ofandSpirulina absorbing-PCL capa- nanofibers, the bility [41]. Alginate (Alg) has a hydrophilic structure that consists of alpha-L- guluronic alginateacid and beta-D-mannuronic was added in aacid, following which can step accommodate due to itslarge high amounts hydrophilicity of water. The and absorbing capabilitystudy revealed [41 that]. Spirulina Alginate extract-alginate (Alg) has saturated a hydrophilic polycaprolactone structure nanofibers that ( consistsSpir- of alpha-L- guluroniculina-Alg/PCL) acid effectively and beta-D-mannuronic accelerated the tissue regeneration acid, which in a rat can model accommodate (3.7% w/v of large amounts ofSpirulina water. extract). The study When this revealed patch was that appliedSpirulina to the extract-alginateanimal’s wounds, the saturated extracellular polycaprolactone matrices were rearranged faster than those treated with the simple patch support without Spirulina. In comparison to the earlier developed Spirulina-PCL nanofibers, alginate improved the moisture preservation and adhesiveness of the Spirulina-Alg/PCL nanofibers, in addition it accelerated the regeneration of full-thickness wounded skin in the rat model.

2.3. Antiacne Acne is an epidermis disorder correlated to a sebum hypersecretion in deformed follicles, which implies inflammation and comedones formation. The anaerobic Cutibacte- rium acnes (also known as Propionibacteriumacnes) plays a role in the inflammation process because it hyperproliferates in the sebaceous lipid environment and produces reactive oxygen species (ROS) and proinflammatory compounds. This cytokine cascade also induces the follicular wall rupture of sebaceous glands and a consequently variation in the sebum composition. Acneic skins are low in linoleic acid and, therefore, their barrier skin function is compromised. Such a lesion pathway may also help the colonization of other bacteria like the Staphylococcus epidermis (S. epidermis). Indeed, although this Staphy- lococcus is a commensal skin microbiome bacterium, it was found in acne as well [55]. Acne disorder affects several people, mostly during adolescence, and it may lead to a lack of the self-confidence, resulting in body shame. Since acne-inducing bacteria shown side effects and an increasing resistance towards the synthetic drugs like tetracycline, many alternative approaches have been explored in the last decades. Among them, the topical applications of cosmetic formulas containing botanicals as safer active ingredients are the more suitable [56]. Currently, the cosmetic market is strongly interested in formulating antiacne products with a special focus on natural active ingredients, in addition to topical medication [57]. With this purpose, in 2018 Nihal et al. developed a topical antiacne formulation using

Cosmetics 2021, 8, 7 12 of 19

nanofibers (Spirulina-Alg/PCL) effectively accelerated the tissue regeneration in a rat model (3.7% w/v of Spirulina extract). When this patch was applied to the animal’s wounds, the extracellular matrices were rearranged faster than those treated with the simple patch support without Spirulina. In comparison to the earlier developed Spirulina- PCL nanofibers, alginate improved the moisture preservation and adhesiveness of the Spirulina-Alg/PCL nanofibers, in addition it accelerated the regeneration of full- thickness wounded skin in the rat model.

2.3. Antiacne Acne is an epidermis disorder correlated to a sebum hypersecretion in deformed follicles, which implies inflammation and comedones formation. The anaerobic Cutibacterium acnes (also known as Propionibacteriumacnes) plays a role in the inflammation process because it hyperproliferates in the sebaceous lipid environment and produces reactive oxygen species (ROS) and proinflammatory compounds. This cytokine cascade also induces the follicular wall rupture of sebaceous glands and a consequently variation in the sebum composition. Acneic skins are low in linoleic acid and, therefore, their barrier skin function is compromised. Such a lesion pathway may also help the colonization of other bacteria like the Staphylococcus epidermis (S. epidermis). Indeed, although this Staphylococcus is a commensal skin microbiome bacterium, it was found in acne as well [55]. Acne disorder affects several people, mostly during adolescence, and it may lead to a lack of the self-confidence, resulting in body shame. Since acne-inducing bacteria shown side effects and an increasing resistance towards the synthetic drugs like tetracycmidrule, many alternative approaches have been explored in the last decades. Among them, the topical applications of cosmetic formulas containing botanicals as safer active ingredients are the more suitable [56]. Currently, the cosmetic market is strongly interested in formulating antiacne products with a special focus on natural active ingredients, in addition to topical medication [57]. With this purpose, in 2018 Nihal et al. developed a topical antiacne formulation using Spirulina extract rich in phycocyanin protein [42]. The latter protein, as already mentioned, is known to be responsible for most of the natural Spirulina benefits. The phycocyanin was successfully extracted from the alga by using sonication and the cold- maceration process and then it was purified by the dialysis method. The authors thus studied its antimicrobial and anti-inflammatory activities. In particular, the antioxidant activity was found to be dependent on phycocyanin concentration in the range between 0.05 and 0.3 mg·mL−1. The antimicrobial property was evaluated, both in an oily-based (FA) and water- based (FB) formula, against Cutibacterium acnes (C. acnes) and S. epidermis, by evaluating the minimal inhibitory concentration (MIC) and the dimension of the zone of inhibition (Table5). The results shown that the water-based formulation was more effective in inhibiting bacteria proliferation than the oily-based one and confirmed the Spirulina antiacne property. More recently, Setyaningsih’s research team further explored the antibacterial activity of a Spirulina-based face mask [43]. Spirulina used in this study was specifically grown to increase the amount of phycocyanins, flavonoids, alkaloids and phenolic compounds, to enhance his anti-inflammatory and antibacterial properties. As reported in Table6, the formula composition includes polyvinyl alcohol and HPMC as polymers, and both extract of Spirulina platensis and its native biomass as active ingredients. During the study, three masks were formulated: the first one with Spirulina, the second one free from any active ingredients and the third one with clindamycin. The latter is a common antimicrobial topic drug and its antibacterial activity against C. acnes was evaluated in vitro. While the free-Spirulina face mask did not affect the bacteria proliferation, a similar inhibition behavior was observed with the alga extract and the synthetic antibacterial drug. Indeed, although the concentration of active ingredients incubated per well was different, the zone of inhibition was comparable: 10 ± 0.4 mm for the Spirulina mask and 12 ± 1.1 mm for the clindamycin one. Cosmetics 2021, 8, 7 13 of 19

Table 5. Composition, characteristic and activity of anti-acne formulations. Published by Ref. [42].

Parameters Oily Formula—(FA) Water Formula—(FB) Paraffin hard (5%) PEG400 (12%) Wool fat (10%) PEG4000 (18%) Cetostearyl alcohol (10%) Stearyl alcohol (28%) Ingredients White soft paraffin (50%) Glycerine (17%) Liquid paraffin (15%) Water (q.s.) Spirulina extract (10%) Spirulina extract (10%) Color-intense blue Color-intense blue Explanation Odor-waxy Odor-odorless Uniformity of weight Comply with the standard Comply with the standard Globule diameter 5.29 mm 5.44 mm pH 6.1 ± 0.06 6.8 ± 0.09

Loss on drying 35c/o w/w 47c/o w/w Consistency Good Good Viscosity 198 ± 0.4 cps 175 ± 0.2 cps Spreadability 8.1 ± 0.11 g·cm/s 8.6 ± 0.12 g·cm/s Diameter of zone of inhibition 23.4 ± 1.0 (P. acne) 26.1 ± 1.2 (P. acne) (mm) 21.3 ± 1.4 (S. epidermis) 24.6 ± 1.6 (S. epidermis) 1.6 ± 0.4 mg/mL (P. acne) 1.5 ± 0.1 mg/mL (P. acne) MIC 2.1 ± 0.6 mg/mL (S. epidermis) 1.8 ± 0.2 mg/mL (S. epidermis)

Table 6. Composition, characteristic and activity of antiacne face mask. Published by Ref. [43].

Parameters Face Mask Methylparaben (0.01 g) HPMC (0.2 g) Glycerine (0.25 g) Ingredients PVA (0.6 g) Distilled water (100 g) Extract of S. platensis (0.25 g) Biomass of S. platensis (0.75 g) color: Green Organoleptic consistency: Semisolid Viscosity 7306.7 ± 9.2 cP pH 6 Spreadability 1.1 cm Homogeneity homogenous Odor Speciﬁc Spirulina Antibacterial activity Positive inhibit C. acnes 10 ± 0.4 Diameter of zone of inhibition (mm) 0 a 12 ± 1.1 b a: Face Mask without Spirulina. b: Face Mask without Spirulina and with clindamycin.

Therefore, Spirulina is shown to be a promising natural cosmetic ingredient with high antibacterial activity against acne pathogens.

3. Spirulina Benchmark Spirulina is the biggest cultivated microalga in the world and it gives rise to over 30% of the worldwide microalgal biomass production [58]. Spirulina is cropped in several countries, Cosmetics 2021, 8, 7 14 of 19

including various African States, Argentina, Burma, Chile, China, Cuba, India, Israel, Japan, Mexico, Myanmar, Pakistan, Thailand, the USA and Vietnam. Japan, the USA and Europe are the main importers of Spirulina powder. As a whole, over 128,000 tons of Spirulina was internationally consumed in 2016, and its revenues reached US$ 718.7 Mn [59]. In the upcoming years the global Spirulina market is expected to grow since its use is rising enormously across the world. The reason behind the overall Spirulina market growth might be to increase awareness about natural food products all over the world, to prefer plant protein sources and to follow the regulation on synthetic colors. Therefore, the market will be estimated at almost US$ 2000 Mn by 2026, with a global Spirulina consumption of more than 321,000 tons [59]. As for the emerging beauty industry, many Spirulina extracts/powders and Spirulina- based products are available on the market, and claim a wide variety of skin-benefits. Furthermore, it is likely that diversity, quality and topical type of applications of Spirulina will rapidly expand in the following years. Considering Spirulina as an active ingredient in the cosmetic industry, dry or liquid concentrated extracts are generally preferred—but not exclusive—over the raw powder of the alga, due to final products functional and esthetical reasons. There is evidence that both properties and behaviors of the Spirulina extracts are strongly influenced by the extraction procedure and by the chosen solvent. Selected commercial suppliers of Spirulina extracts/powders are reported in Table7.

Table 7. Selected commercial Spirulina extracts/powders for skin care applications.

Company Type Key Benefits/Claims Ref. Bio-Botanica (USA) Hydroglyceric liquid Spirulina platensis extract Skin conditioning benefits [60] Sensient Cosmetic Dry extract of Spirulina platensis supported in Antioxidant potential with radiant skin [61] Technologies (France) dextrin, sodium citrate and sodium phosphate effect and revitalizing benefits Antiradical, anti-inflammatory, SEPPIC (France) Water-blue algae extract [62] photoprotective and cells renewal effects Water Spirulina platensis extract, stabilized by citric Phenbiox (Italy) Antioxidant potential [63] acid, sodium benzoate and potassium sorbate

Bio-Botanica (USA) produces a liquid blend of Spirulina platensis extract in glycerin and water. This extract offers skin conditioning benefits and can be used in a variety of personal care formulations [60]. NatPure® APX, developed by Sensient Cosmetic Technologies (Saint-Ouen-l’Aumône, France-headquarter), is instead a dry extract of Spirulina platensis supported in dextrin, sodium citrate and sodium phosphate, and has antioxidant potential with a radiant skin effect and revitalizing benefits [61]. Spiruline AP® is a water-soluble blue algae extract, supplied by SEPPIC (France-headquarter). This brand claims that its extract has excellent antiradical, anti-inflammatory, photoprotective and cells renewal effects. It may be used as an active ingredient for antiaging skin products [62]. In Italy, a water Spirulina platensis extract—stabilized by citric acid, sodium benzoate and potassium sorbate—is supplied by Phenbiox [63]. The fact that more Spirulina extracts/raw material for cosmetics are currently on the market further demonstrates that the interest of the sector in this alga is rising. Some relevant commercial examples of Spirulina-based cosmetic products are listed in Table8. Looking at the current beauty products available in the market, Spirulina—mainly S. platensis and S. maxima—is used either as a powder, generally in cheaper products, or as a phycocyanin-rich blue extract, particularly in the luxury market. Overall, most of the cosmetics available on the market claim a large range of Spirulina benefits, including antiaging, revitalizing, remineralizing, moisturizing, protecting alongside cleansing and shining action, for both hair and skin. Furthermore, while some of the claims like “mattifying” or “purifying” are probably due to the whole blend of the ingredients, the moisturizing and illuminating effects may be directly attributed to the Spirulina action instead. Cosmetics 2021, 8, x FOR PEER REVIEW 15 of 20 Cosmetics 2021, 8, x FOR PEER REVIEW 15 of 20

Table 7. Selected commercial Spirulina extracts/powders for skin care applications. Table 7. Selected commercial Spirulina extracts/powders for skin care applications. Company Type Key Benefits/Claims Ref. Bio-BotanicaCompany (USA) Hydroglyceric liquid SpirulinaType platensis extract SkinKey conditioning Benefits/Claims benefits [Ref.60] SensientBio Cosmetic-Botanica Technologies (USA) DryHydroglyceric extract of Spirulina liquid Spirulina platensis platensis supported extract in AntioxidantSkin conditioning potential with benefits radiant [60] Sensient Cosmetic Technologies Dry extract of Spirulina platensis supported in Antioxidant potential with radiant [61] (France) dextrin, sodium citrate and sodium phosphate skin effect and revitalizing benefits [61] (France) dextrin, sodium citrate and sodium phosphate Antiradical,skin effect anti and-inflammatory, revitalizing benefits photo- SEPPIC (France) Water-blue algae extract Antiradical, anti-inflammatory, photo- [62] SEPPIC (France) Water-blue algae extract protective and cells renewal effects [62] Water Spirulina platensis extract, stabilized by cit- protective and cells renewal effects Phenbiox (Italy) Water Spirulina platensis extract, stabilized by cit- Antioxidant potential [63] Phenbiox (Italy) ric acid, sodium benzoate and potassium sorbate Antioxidant potential [63] ric acid, sodium benzoate and potassium sorbate Bio-Botanica (USA) produces a liquid blend of Spirulina Platensis extract in glycerin and water.Bio-Botanica This extract (USA) offers produces skin conditioninga liquid blend benefits of Spirulina and canPlatensis be used extract in a invariety glycerin of personaland water. care This formulations extract offers [60]. skin NatPure conditioning® APX, devel benefitsoped andby Sensient can be used Cosmetic in a varietyTechnol- of ogiespersonal (Saint care-Ouen formulations-l’Aumône [60, France]. NatPure-headquarter),® APX, devel isoped instead by Sensient a dry extract Cosmetic of Spirulina Technol- platensisogies (Saint supported-Ouen -inl’Aumône dextrin, ,sodium France -citrateheadquarter), and sodium is instead phosphate, a dry and extract has antioxidant of Spirulina potentialplatensis supportedwith a radiant in dextrin, skin effect sodium and revitacitratelizing and sodium benefits phosphate, [61]. Spiruline and APhas® antioxidantis a water- solublepotential blue with algae a radiant extract, skin supplied effect and by SEPPICrevitalizing (France benefits-headquarter). [61]. Spiruline This AP brand® is a claims water - thatsoluble its extract blue algae has excellentextract, supplied antiradical, by antiSEPPIC-inflammatory, (France-headquarter). photoprotective This brandand cells claims re- newalthat its effects. extract It hasmay excellent be used antiradical,as an active anti ingredient-inflammatory, for antiaging photoprotective skin products. and [cells62]. Inre- Italy,newal a effects.water Spirulina It may be platensis used as extractan active—stabilized ingredient by for citric antiaging acid, sodiumskin products. benzoate [62 and]. In potassiumItaly, a water sorbate Spirulina—is supplied platensis by extract Phenbiox—stabilized [63]. by citric acid, sodium benzoate and potassiumThe fact sorbate that more—is suppliedSpirulina byextracts/raw Phenbiox [material63]. for cosmetics are currently on the Cosmetics 2021, 8, 7 marketThe further fact that demonstrates more Spirulina that theextracts/raw interest of material the sector for in co thissmetics alga areis rising. currently Some on rel- the15 of 19 evantmarket commercial further demonstrates examples of that Spirulina the interest-based ofcosmetic the sector products in this are alga listed is rising. in Table Some 8. relevant commercial examples of Spirulina-based cosmetic products are listed in Table 8. Table 8. Spirulina benchmark on skin care products. TableTable 8. Spirulina 8. Spirulina benchmarkbenchmark on skin on skincare careproduct products.s. Cosmetic Product INCI Spirulina Key Benefits/Claims Company Product’s Photo Ref. CosmeticCosmetic Product ProductINCI INCI SpirulinaSpirulina KeyKey Benefits/Claims Beneﬁts/Claims CompanyCompany Product’sProduct’s Photo Photo Ref.Ref.

PuroBIO cosmetics KELLY powder mask S. platensis powder Peel-off for dry skin [64] KELLY powder PuroBIOPuroBIO(Bari, cosmetics Italy)cosmetics KELLY powder mask S. platensisS. platensis powderpowder Peel Peel-off-off for for dry dry skin skin [64[64] ] mask (Bari,(Bari, Italy) Italy)

Antiaging serum, balancing cleans- SpirulinaCosmetics Santè 2021 Methode, 8, x FOR PEER REVIEW Antiaging serum, balancing Santè Naturels (Mi- 16 of 20 Cosmetics Spirulina2021, 8, x FORSant PEERè S. maxima REVIEW extract ingAntiaging milk, restorative serum, ba tonic,lancing antioxi- cleans- Santè Naturels 16 of 20[ 65] Spirulinaface Santè line Methode S. maxima extract cleansing milk, restorative Santèlano, Natur Italy)els (Mi- [65] Cosmetics Methode 20212021,, 88,, xxface FORFORline PEERPEERS. maximaREVIEWREVIEW extract ing milk, restorativedant tonic, antioxi- (Milano, Italy) 1616 ofof 2020 [65] Cosmeticsface line 2021 , 8, x FOR PEER REVIEW tonic, antioxidant lano, Italy) 16 of 20 dant

Face, hand, milk cream, DONI DEL MARE - Face, hand, milk cream, Regenerating, moisturizing, anti- DONI DEL MARE - SPF 50 +/30/15, after sun, S. maxima extract HAZE COSMETICS [66] Face, hand, milkFace, cream, hand, milk Regenerating, moisturizing, anti- DONI DEL MARE -- SPFFace, 50 hand, +/30/15, milk after cream, sun, S. maxima extract Regenerating,aging moisturizing,properties anti- HAZEDONIDONI DEL COSMETICS MARE - [66] SPFhair 50 +/30/15,oil, tanningcream, after oil sun,SPF 50 S. maxima extractextract Regenerating,Regenerating,aging moisturizing,properties moisturizing, anti- (Milano,HAZE CO uniPV,SMETICS Italy) [[6666]] SPFhair 50 +/30/15,oil, tanning after oil sun, S. maximaS. maxima extractextract agingaging propertiesproperties -HAZE(Milano,HAZE COSMETICSCO uniPV,SMETICS Italy) [66[66] ] hair oil, tanning+/30/15, oil after sun, antiagingaging properties properties (Milano,(Milano, uniPV,uniPV, Italy)Italy) hair oil, tanning oil (Milano,(Milano, uniPV,uniPV, Italy)Italy) hair oil, tanning oil

ELLA BACHÈ Crème spiruline liftante Wrinkle-lifting and anti-aging with ELLA BACHÈ Crème spiruline liftante S. maxima extract Wrinkle-lifting and anti-aging with NutridermologieELLA BACHÈ — [67] Crème spirulinerides liftante S. maxima extract Wrinkle-progressiveliftingWrinkle-lifting and anti action-aging and with NutridermologieELLAELLA BACHBACHÈÈ — [67] Crème spirulineridesCr è meliftante spiruline Wrinkle-progressivelifting and anti action-aging with (Paris,ELLA BACHÈFrance) Crème spiruline liftante S. maximaS. maxima extractextractextract Wrinkleanti-aging-lifting and with anti progressive-aging with NutridermologieNutridermologie—— [67[[6767] ]] ridesrides liftante rides S. maxima extract progressive action Nutridermologie(Paris, France) — [67] rides progressiveaction action (Paris,(Paris, France)France) (Paris,(Paris, France)France)

Immediate brightness effect. The Institut ES- Immediate brightness effect. The Institut ES- Face cream, face serum S. maxima extract skin isImmediate more toned, brightness and smooth, effect. vis- THEDERM—(Paris, [68] ImmediateImmediate brightnessbrightness effect.effect. TheThe InstitutInstitutInstitut ES-ES- Face cream, Faceface serum cream, faceS. maxima extract skinImmediate isThe more skin toned,brightness is more and toned, smooth,effect. and The vis- THEDERMInstitut— ES-(Paris, [68] Face cream, face serum S. maximaS. maxima extractextractextract skinskinibly isis moremorenourished toned,toned, and andand revitalized smooth,smooth, vis-vis- THEDERMESTHEDERM—France)— (Paris,(Paris, [68[[6868] ]] Face cream, face serumserum S. maxima extract skinibly issmooth, morenourished toned, visibly and and nourishedrevitalized smooth, vis- THEDERMFrance)—(Paris, [68] iblyibly nourishednourished andand revitalizedrevitalized (Paris,France) France) ibly nourishedand revitalized and revitalized France)

EffectiveEffective against against blemishes. blemishes. It mini- EffectiveIt minimizes against blemishes. the appearance It mini- Mattifying, purifyingMattifying, clay Effectivemizes the against appearance blemishes. of pores, ItIt mini-mini- re- Mattifying, purifying clay S. platensis powder Effectivemizes ofthe pores,against appearance removes blemishes. of excesspores, It mini- re- REN Skin care—(UK) [69] Mattifying,mask purifyingpurifying clay clay S. platensisS. platensis powderpowder movesmizes excessthe appearance sebum and of fightspores, con- re- RENREN SkinSkin care—(UK)care—(UK) [69[69] ] Mattifying,mask purifying clay S. platensis powder movesmizes excessthe sebumappearance sebum and and ﬁghts of fightspores, con-re- REN Skin care—(UK)(UK) [[6969]] mask mask S. platensis powder movesgestion, excess without sebumebum drying andand the fightsfights skin con-con- out REN Skin care—(UK) [69] mask movesgestion,congestion, excess without sebum drying without and the fights drying skin con- out gestion, without drying the skin out gestion, withoutthe drying skin out the skin out

Marin Complex Marin Complex Deep Re- Restore Restoreand rejuvenate and rejuvenate without risk Marin ComplexDeep Deep Restorative Re- S. maximaS. maxima extractextract Restore and rejuvenate without risk Zelens—(UK)Zelens—(UK) [70[70] ] Marinstorative Complex Cream Deep Re- S. maxima extract Restorewithout and ofrejuvenate irritation risk of irritation without risk Zelens—(UK) [70] Marinstorative Complex Cream DeepCream Re- S. maxima extractextract Restore and ofrejuvenate irritation without risk Zelens—(UK)(UK) [[7070]] storativestorative CreamCream S. maxima extract of irritation Zelens—(UK) [70] storative Cream of irritation

Powercell Skinmunity Stimulates revitalization, smoothes HELENA RUBIN- Powercell Skinmunity S. platensis extract Stimulates revitalization, smoothes HELENA RUBIN- [71] PowercellEmulsion Skinmunity S. platensis extract wrinkles,Stimulates intensely revitalization, hydrates smoothes the skin STEINHELENA—(Australia) RUBIN- [71] PowercellEmulsion Skinmunity S. platensis extraextractct wrinkles,Stimulates intensely revitalization, hydrates smoothes the skin STEINHELENA—(Australia) RUBIN- [[7171]] Emulsion S. platensis extract wrinkles, intensely hydrates the skin STEIN—(Australia)(Australia) [71] Emulsion wrinkles, intensely hydrates the skin STEIN—(Australia)

Nourishing, revitalizing, moisturiz- SUKIN SKINCARE— Face cream, face serum S. platensis extract Nourishing, revitalizing, moisturiz- SUKIN SKINCARE— [72] Face cream, face serum S. platensis extract Nourishing,ing, antioxidant, revitalizing, detox moisturiz- SUKIN(Australia) SKINCARE — [72] Face cream, face serum S. platensis extractextract Nourishing,ing, antioxidant, revitalizing, detox moisturiz- SUKIN(Australia) SKINCARE — [[7272]] Face cream, face serum S. platensis extract ing,ing, antioxidant,antioxidant, detoxdetox (Australia)(Australia) [72] ing, antioxidant, detox (Australia)

Looking at the current beauty products available in the market, Spirulina—mainly S. Looking at the current beauty products available in the market, Spirulina—mainly S. platensisLoo andking S. at maximathe current—is usedbeauty either products as a powder, available generally in the market, in cheaper Spirulina products,—mainly or asS. platensisLoo kingand S.at maximathe current—is usedbeauty either products as a powder, available generally in the market, in cheaper Spirulina products,—mainly or asS. aplatensis phycocyanin and S.- richmaxima blue— isextract, used eitherparticularly as a powder, in the luxurygenerally market. in cheaper Overall, products, most of or t heas platensisa phycocyanin and S.- richmaxima blue— isextract, used eitherparticularly as a powder, in the luxurygenerally market. in cheaper Overall, products, most of or t heas a phycocyanin-rich blue extract, particularly in the luxury market. Overall, most of the a phycocyanin-rich blue extract, particularly in the luxury market. Overall, most of the

Cosmetics 2021, 8, x FOR PEER REVIEW 16 of 20

Face, hand, milk cream, DONI DEL MARE - Regenerating, moisturizing, anti- SPFFace, 50 hand, +/30/15, milk after cream, sun, S. maxima extract HAZEDONI DELCOSMETICS MARE - [66] Regenerating,aging moisturizing,properties anti- SPFhair 50 +/30/15,oil, tanning after oil sun, S. maxima extract (Milano,HAZE CO uniPV,SMETICS Italy) [66] aging properties hair oil, tanning oil (Milano, uniPV, Italy)

ELLA BACHÈ Crème spiruline liftante Wrinkle-lifting and anti-aging with S. maxima extract NutridermologieELLA BACHÈ — [67] Crème spirulinerides liftante Wrinkle-progressivelifting and anti action-aging with S. maxima extract Nutridermologie(Paris, France) — [67] rides progressive action (Paris, France)

Immediate brightness effect. The Institut ES- Face cream, face serum S. maxima extract skinImmediate is more toned,brightness and smooth,effect. The vis- THEDERMInstitut— ES-(Paris, [68] Face cream, face serum S. maxima extract skinibly is morenourished toned, and and revitalized smooth, vis- THEDERMFrance)—(Paris, [68] ibly nourished and revitalized France)

Effective against blemishes. It mini- Mattifying, purifying clay Effectivemizes the against appearance blemishes. of pores, It mini- re- S. platensis powder REN Skin care—(UK) [69] Mattifying,mask purifying clay movesmizes excessthe appearance sebum and of fightspores, con-re- S. platensis powder REN Skin care—(UK) [69] mask movesgestion, excess without sebum drying and the fights skin con- out gestion, without drying the skin out

Cosmetics 2021, 8, 7 16 of 19

Marin Complex Deep Re- Restore and rejuvenate without risk S. maxima extract Zelens—(UK) [70] Marinstorative Complex Cream Deep Re- Restore and ofrejuvenate irritation without risk S. maxima extract Zelens—(UK) [70] storative Cream of irritationTable 8. Cont.

Cosmetic Product INCI Spirulina Key Beneﬁts/Claims Company Product’s Photo Ref.

Powercell Skinmunity Stimulates revitalization, smoothes HELENA RUBIN- S. platensis extract [71] PowercellEmulsion SkinmunityPowercell wrinkles,StimulatesStimulates intensely revitalization, revitalization, hydrates smoothes the skin STEINHELENAHELENA—(Australia) RUBIN- Skinmunity S. platensisS. platensis extractextract smoothes wrinkles, RUBINSTEIN— [71[71] ] Emulsion wrinkles, intensely hydrates the skin STEIN—(Australia) Emulsion intensely hydrates the skin (Australia)

Nourishing, revitalizing, Face cream, face Nourishing, revitalizing, moisturiz- SUKIN SKINCARE—SKINCARE— Face cream, face serum S. platensisS. platensis extractextract moisturizing, antioxidant, [72[72] ] serum Nourishing,ing, antioxidant, revitalizing, detox moisturiz- SUKIN(Australia)(Australia) SKINCARE — Face cream, face serum S. platensis extract detox [72] ing, antioxidant, detox (Australia)

Looking at the current beauty products available in the market, Spirulina—mainly S. 4. Conclusions and Future Perspectives platensisLoo kingand S.at maximathe current—is usedbeauty either products as a powder, available generally in the market, in cheaper Spirulina products,—mainly or asS. platensisa phycocyanin andAs hereinS.- richmaxima reviewed,blue— isextract, usedSpirulina eitherparticularly asis a powder, potential in the luxurygenerally bioactive market. in ingredient, cheaper Overall, products, for most developing of or t heas ef- a phycocyaninfective and-rich safe blue cosmetics. extract, Inparticularly recent years in the the luxury skin-care market. benefits Overall, of Spirulina most ofproducts the have been investigated by both academics and company researchers. Spirulina contains a set of synergistically acting components, such as peptides, polyunsaturated fatty acids, vitamins, minerals and antioxidant phytonutrients, which provide a full healthy action to the formulation. Several Spirulina extracts/powders and alga-based skin care products are available on the market and this field is expected to further grow in the following years. As a formulating ingredient, Spirulina—S. platensis or S. maxima, as the major genes—is used as a dry or liquid concentrated phycocyanin-rich blue extract in the luxury products, or as raw powder in the cheaper formulations. A number of topical Spirulina-based formulations claim a large range of behaviors, including antioxidant, revitalizing, remineralizing, moisturizing, protecting alongside cleansing and shining action, for both hair and skin. Therefore, these products might be topically used like a booster of hydration, antiwrinkles, antiaging and antiacne agents. At the same time, Spirulina might be incorporated in skin-care formulations to promote healthy sunscreen protection, to treat skin pigmentation disorders and to achieve wound healing benefits. Despite the recent progress, the topic should be further investigated: other skin benefits, actions or applications might occur and the role of the phytocomplex and its action pathways need a further exploration. In addition, the human health risks (skin-toxicity, allergies, etc.) should also be studied in greater depth to refine cosmetic spirulina-based products in the long-term. For instance, the antibacterial activity of Spirulina might suggest to study how this alga affects the skin microbiome in deeper details. Taking care of skin commensal bacteria, thus avoiding skin dysbiosis, is an emerging topic in both cosmetic and dermatological fields. Skin dysbiosis is correlated to the incidence rate of skin disease, due to the hy- perproliferation of some bacteria that normally colonize hair follicles and glands [73]. To conclude, there is a need to pursue research about Spirulina antimicrobial skin activity to further support the use of this microalga for the treatment of skin dysbiosis.

Author Contributions: Conceptualization, I.R., G.N.N., S.Z. and E.A.; writing—original draft preparation, I.R. and E.A.; writing—review and editing, I.R. and E.A.; project administration, E.A., W.B. and S.Z.; funding acquisition, W.B. All authors have read and agreed to the published version of the manuscript. Cosmetics 2021, 8, 7 17 of 19

Funding: This research was funded by Labomar S.p.a. Acknowledgments: The author would like to thank Alessia Marcato for her help in editing the manuscript. Conﬂicts of Interest: The authors declare no conﬂict of interest.

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