Microalgae and Cyanobacteria Exopolysaccharides: An Untapped Raw Material for Cosmetic Use

Abstract

Microalgae and cyanobacteria produce extracellular polysaccharides that are exuded and released into the medium, typically referred to as exopolysaccharides (EPSs). Microalgae-derived EPSs have garnered attention in the last decade, as they may exhibit specific bioactivities and therefore hold promise for biofunctional applications in the biomedical, food, agricultural, and cosmetic fields. In cosmetic formulations, EPSs can be included both to improve techno-functional and sensorial properties and as active ingredients, showing great potential in the preparation of cosmetic products aimed at hydration and anti-aging. This review surveys the literature on the potential of EPS microalgae in skin care and cosmeceutical formulations to reveal a material that is sometimes discarded during the microalgae cultivation process and that can be recovered for cosmetic use. The conclusions of this review highlight that EPSs from microalgae and cyanobacteria exhibit different physicochemical and biological functionalities, making them attractive for potential exploitation as commercial sources of new polysaccharides.

1. Introduction

Algae can be regarded as cost-effective renewable resources with higher photosynthetic efficiency and productivity than terrestrial biomass. They can promote carbon neutrality since they can be grown in non-arable land with non-potable water, even in a low-cost or waste culture medium [1,2]. In addition, they can be cultivated using cheap substrates of carbon dioxide from industrial emissions, wastewaters, and saline waters [3].

Compared to macroalgae, microalgae offer advantages in large-scale cultivation, as they can be grown rapidly under controlled conditions, without the constraints of seasonal variation or restrictive coastal laws. They also have the advantage of being able to be cultivated in closed photobioreactors or open pond systems, allowing for sustainable and scalable production of polysaccharides (PSs). These characteristics, combined with the growing global interest in bioactive natural products, position microalgal PSs as a promising resource for next-generation biotechnological innovations aimed at improving human health and well-being [4]. Therefore, in recent years, there has been an increase in publications regarding microalgae-derived PSs and their bioactivity, aimed at improving their growth and purification, with the aim of their use in the food and cosmetics industries.

Microalgae and cyanobacteria are microorganisms that produce a wide range of high-value functional and bioactive compounds, such as lipids, polyunsaturated fatty acids, pigments, vitamins, proteins/peptides, carbohydrates, and exopolysaccharides, among others [5,6]. These microbial autotrophs produce and secrete extracellular polymeric substances, mainly consisting of PSs, but in this surrounding biofilm, proteins, nucleic acids, and lipids may also be present [7]. These diverse extracellular PSs can be released to the medium as a by-product [3].

Microalgae and cyanobacteria contain PSs on their outer cell surface (as their main constituent of the cell wall), which forms a protective gel-like matrix to protect the microalgae from different environmental stressors, such as temperature changes, UV radiation, and predation [8]. Most microalgal and cyanobacterial extracellular polysaccharides are heteropolymers with complex chemical structures, consisting of glucose, galactose, and xylose; other monosaccharides, such as rhamnose, iduronic acid, and fucose; and different sulfate content. These eukaryotic and prokaryotic microbial PSs have various biological functions, protection from fluctuations in environmental conditions and/or predators, sorption of organic and/or inorganic compounds, adhesion, biofilm, protection from antimicrobial agents, exportation of cell components, water retention and protection against desiccation, and bacteria aggregation, being also pioneers in the colonization of soils and a nutrient source for a bacterial community [9,10,11]. Cyanobacterial PSs could protect from harmful effects of oxygen and serve as a chelator for iron and calcium [12]; aid in the fixation of nutrients, locomotion, attachment to solid substrates, and formation of colonies; and especially provide protection against adverse conditions and predators, sorption of organic and/or inorganic compounds, binding of enzymes, a sink for excess energy, adhesion, biofilm, water retention, aggregation, a nutrient source for a bacterial community adhesive, structural protection against abiotic stress and bio-weathering processes, gliding motility, and nutrient repositories in phototrophic biofilms or biological soil crusts [11,13,14].

These extracellular polysaccharides that are exuded and released to the medium are usually denoted as exopolysaccharides, extracellular, exocellular, or released polysaccharides (R-EPSs). However, part of the polysaccharides is not completely excreted into the medium and remains more or less attached to the cell surface (also known as bound-EPS, (B-EPS)) [10,11,15]. Those produced from cyanobacteria can be divided into (i) slime or released polysaccharides, poorly linked to the cell surface; (ii) sheath polysaccharides in a thin layer next to the outer cell membrane; and (iii) capsular polysaccharides (CPSs) that are tightly bound [10,13,16,17].

For extracellular polysaccharide extraction and purification, different methods can be used. Alcoholic precipitation with coprecipitation of salts to obtain R-EPSs gives a low-purity product, so to achieve higher purity, purification techniques, such as dialysis or ultrafiltration, are used, combined with alcoholic precipitation. Different chemical methods, such as acid or alkali extraction (using ethylene diamine tetra acetic acid (EDTA) or sodium hydroxide), and physical methods, such as hot water extraction or cationic resins, are used for releasing B-EPSs before proceeding with alcoholic precipitation [8].

Since EPSs derived from these natural sources are nontoxic, biodegradable, and biocompatible, they represent an alternative source of polysaccharides [18,19]. When used in cosmetics, EPSs from microalgae and cyanobacteria can be a good alternative to EPSs from other natural sources, such as cereals, since they can be obtained during the processes used to obtain other biocompounds from microalgae (growth, extraction, and purification). Their recovery and valorization contribute to the economic and environmental compatibility and sustainability of zero-waste microalgal biorefineries [20]. However, EPS-derived commercial products are still being developed, and significant research remains to be completed [21].

The increasing interest in the production of value-added compounds and biofuels from algae requires the production of microalgal biomass. The extracellular polysaccharide produced simultaneously with biomass and secreted to the culture medium in the algal culture process remains as a by-product in waste liquid streams, which are often discarded into the environment. They can be valorized, thus reducing the production cost of microalgae lipids for preparing biodiesel [7,22]. At the end of cell growth, the medium is generally regarded as waste [23], so the recovery of R-EPSs from a spent cultivation medium is a practicable proposition in a bio-refinery-like approach to Spirulina sp. cultivation [8].

The ease of recovery from the extracellular environment has increased the attention of researchers on EPSs for applications in different sectors based on their biocompatibility, biodegradability, and unique rheological and biological properties [24]. Microalgae and cyanobacteria can produce exopolysaccharide compounds which exhibit various physico-chemical properties, including stabilizing, thickening, gelling, texturizing, flocculating, emulsifying, and water retention properties, which are of interest for a range of industrial applications in cosmetics, textiles, pharmaceuticals, adhesives, detergents, food additives, and wastewater treatment [25,26,27]. In addition, these EPSs exhibit biological properties, including antioxidant, anti-inflammatory, antimicrobial, antiviral, antiproliferative, antihypertensive, antilipidemic, anti-diabetic, and immunomodulatory properties [28,29], with applications in cosmetics, pharmaceuticals, nutraceuticals, and functional foods [1,15,30,31].

Their mechanical properties can offer commercial applications, including as a bio-lubricant, emulsifier, foaming agent, and thickener and in water retention activity [7,24], but they are not competitive with those from other sources. Their wide variety of biological activities, biodegradability, natural origin, and nontoxicity make them ideal bioactive compounds to be used in the cosmetic and health care industry [7,15].

Despite the unique composition and structure and with the interesting rheological and biological activities of EPSs from microalgae and from cyanobacteria, the research on seaweed polysaccharides is intense, as is their industrial exploitation [32,33]. Due to their higher production costs compared to polysaccharides from terrestrial plants and macroalgae, only microbial polysaccharides with unique properties, having a niche market, are commercialized, and this could be the case for microalgal and cyanobacterial EPSs [10,15]. Therefore, improving the processes for obtaining/separating EPSs from microalgae and cyanobacteria for use in cosmetics may be one of the objectives of industries linked to microalgae production, whether for cosmetic or nutritional use.

As Pierre et al. [11] have proposed, low-market-value industrial products are not the best option for microalgal EPSs because their production costs remain 10–100 times higher than for terrestrial, bacterial, and seaweed polysaccharides. In the cited review, the following question is asked: why is there a lack of knowledge about EPSs from microalgae? The answer is that the culture of these microorganisms is often complex and difficult (notably for eukaryotic microalgae) compared with heterotrophic cultures of non-photosynthetic microorganisms. Furthermore, their generation time is high, most of them are not axenic, the biomass concentration is very low after autotrophic cultures, and some microalgae can require unknown (or poorly controlled) culture conditions (e.g., irradiance and composition of culture media) [11]. Other microbial polysaccharides have become commercially relevant and have overcome production costs by operating in a niche market. Some pharmaceutical and cosmetic high-value applications could have potential. The need for well-defined polysaccharidic structures and authorizations required in pharmaceutical applications makes this market not yet adequate for microalgae polysaccharides. Although the cosmetic market could receive polysaccharides of microalgae, only a small number of examples are commercialized, for example, EPSs from red microalgae or spirulan from Arthrospira strains [11,13]. There is interest in screening algal strains for new polysaccharides that may compete with traditional polysaccharides for rheological properties and bioactivities, as well as for their integration into nanobiotechnology applications for stabilization of nanostructures with antimicrobial, antioxidant, and/or anticancer properties [19,26].

Several recent reviews have addressed strategies for sustainable production, recovery, purification, chemical and structural determination, biological activities, and applications of EPSs obtained from microalgae and cyanobacteria [1,2,4,6,9,10,13,15,24,27,30,34,35,36]. The main opportunities and challenges in relation to the manufacturing of these compounds have also been explored. Also, insights into the main challenges and future prospects for market investments were surveyed [11,26]. In any case, their use in cosmetics as active ingredients is still limited.

Figure 1 summarizes the key steps in microalgal polysaccharide production and extraction and their biofunctional applications.

2. Composition and Structure

Microalgae and cyanobacteria EPSs are complex heteropolymers. Their composition varies between 3 and 8 monosaccharides, with a variety of substituents and sulfation and a high molecular mass of around 10⁶ Da [15]. The diversity of monosaccharide constituents, the presence of non-sugar substituents, the apparent absence of repeating units, and the branched structure collectively complicate their characterization.

EPSs from microalgae and cyanobacteria are heteropolymers mainly composed of xylose, glucose, and galactose in different ratios [33]. Other sugar constituents, such as mannose, rhamnose, arabinose, fucose, fructose, and ribose, are also present. The polymers have different sulfate contents (1–9%, w/w), with the sulfate groups being attached to glucose and galactose in the 6 or 3 position [9]. Minor components have also been reported, e.g., the Porphyridium sp. mucilaginous polysaccharide; it is generally composed of about ten monosaccharides, sulfate, and other biocompounds, such as proteins and possibly phenols [68].

The composition of some EPSs is variable from species to species and sometimes affected by growth conditions, recovery, and purification/analysis methods [10,15]. Thus, the compositions can vary both with culture conditions and with the methodology used for extraction and quantification [33].

Their chemical and structural complexity has received limited research attention despite the critical need to determine potential applications [4,18]. The variations in monosaccharide compositions have also resulted in different physicochemical and biological functionalities. Their composition (type and contents of monosaccharides) influences their bioactivity and also structural features, such as sulfate groups for antiviral, antitumor, anti-inflammatory, anti-oxidative, and antiviral activities.

Some examples are as follows: uronic acids will confer a negative charge to the polymer, which can influence biological and/or physico-chemical properties. The presence of non-sugar components is also of great importance because they can also influence these properties. Methyl groups can cause high viscosity via hydrophobic interactions [24], and sulfate content is another important component and could be responsible for important bioactivities. For instance, in red microalgal species, the highest antiviral activity was found in the polysaccharide having the highest sulfate content [9]. The other unique feature of cyanobacterial strains exposed to high sunlight areas is the presence of scytonemin, mycosporine, and other metabolites found in capsule-bound EPSs [24].

On the other hand, there is growing interest in the large-scale production of cyanobacterial EPSs due to their potential industrial applications, such as their use as gums, bio-flocculants, soil conditioners, and biosorbents. Some commercial examples are Nostoflan, Spirulan, Immulan, and Emulcyan, produced by Nostoc flagelliforme, Arthrospira platensis, Aphanotece halophytica, and Phormidium, respectively [13]. Other cyanobacterial EPSs also deserve mention, such as cyanoflan from Cyanothece sp. [69] and sacran from Aphanothece sacrum, which increase the viscosity of aqueous solutions and can therefore act as emulsifiers or thickeners [24].

3. Properties of EPSs of Interest for Skin Care Products

In the formulation of cosmetic and cosmeceutical products, different ingredients are required, including (i) those conferring techno-functional and sensorial properties, including thickeners, emulsifiers, antioxidants, preservatives, etc., and (ii) the active ingredients responsible for the final action of the product.

Figure 2 summarizes the main composition of cosmetics and cosmeceuticals.

3.1. Techno-Functional Properties of Microalgal EPSs

Microalgal and cyanobacterial EPSs exhibit mechanical properties of interest for the formulation of cosmetics and with the potential to replace those from chemical synthesis.

Rheological properties of EPSs are of deep interest since they can be used as excipients as well as gelling agents, thickeners, etc.

The presence of acidic components has been related to their protective role against desiccation due to their water-retaining ability [3]. The development of novel and specific applications based on their weak gel behavior is expanding. Furthermore, their combination of cell wall polysaccharides and microalgal biomass to merge both structural and bioactive properties has been proposed for food applications [70]. For instance, a solution with 1% of an EPS from whey wastewater-cultivated Chlorella vulgaris showed rheological profiles similar to those of 0.4% commercial xanthan gum [21], one of the most used gelifying agents in organic cosmetics. The rheological properties of microalgae and cyanobacteria EPSs are comparable to those of industrial polysaccharides, such as xanthan, making them suitable for industrial applications [71].

Extracellular polymeric substances can be alternative encapsulating agents, a cosmetic use on the rise, so controlled release systems made of EPSs may have potential use in cosmetics and nutraceuticals. Estevinho et al. used an EPS from the marine cyanobacterium Cyanothece sp. CCY 0110 to encapsulate vitamin B₁₂ in spherical, 8 μm microparticles, and the addition of Arabic gum allowed for smaller sizes [72].

EPSs from microalgae may also be used as emulsifying agents and stabilizers. Phormidium J-1, a hydrophobic, benthic cyanobacterium, produced a polymeric extracellular emulsifying agent called emulcyan [73], which can be regarded as a renewable and eco-friendly emulsifying agent [74]. Exopolymers from the cyanobacterium Nostoc muscorum at 1% in hydrocarbons and vegetable oils exhibited good emulsifying properties with excellent stability [75]. Their anti-settling properties have also been confirmed; rhamnofucan EPSs from Glossomastix sp. have been proposed as anti-settling stabilizers, showing more stable microcrystalline cellulose particle suspensions than alginate solutions [71].

Microalgae and cyanobacteria EPSs are also being investigated as preservatives and antioxidant additives in skin care product formulations. Cosmetic antimicrobial preservatives are ingredients added to beauty and personal care products to prevent microbial growth, which can lead to spoilage, product degradation, and potential health risks, aimed to extend the shelf life of products and ensure they remain safe for use over time. A green cosmetic formulation seeks antimicrobial preservatives that are less harmful and safer, and algal EPSs can fulfill this function. One of the most well-known antimicrobials is calcium spirulan from Arthrospira platensis, which shows strong antiviral activity [76,77].

Other preserving additives are antioxidants, which are needed to protect from oxidation and to prolong the shelf life of lipid-containing products. They can be of interest in cosmetics to prevent lipid oxidation; for example, sulfated algal EPSs can prevent the accumulation of free radicals and reactive species [10], with significant reducing and antiradical properties, although lower than those of ascorbic acid [25].

3.2. Microalgal EPS Bio-Activities

Biological properties of EPSs have been investigated, mainly for pharmacological and nutritional purposes. Several studies showed the anti-inflammatory [31,78], antitumor [4,14,79], anti-hyperglycemic [68], anticoagulant [80], and the aforementioned antioxidant activities [10,25]. Other actions have been reported, including antitussive and bronchodilator effects [40,81] and immunomodulatory activities [82].

Another field of interest is the use of microalga EPSs as a source of prebiotics, both for nutraceuticals and cosmetics. In one review, Gouda et al. [83] proposed that microalgae may be an important source of prebiotics, contributing xylooligosaccharides, galactooligosaccharides, alginatooligosaccharides, neoagarooligosaccharides, galactans, arabinoxylans, and β-glucans; therefore, they could be used as dietary prebiotics with the aim of stimulating probiotic bacterial growth in the gut and colon.

All of this leads us to conclude that EPSs can be included in cosmetic formulations as active ingredients, exerting antioxidant, anti-inflammatory, and immunomodulatory activities. Section 4 summarizes the potential uses of EPSs in cosmetics and cosmeceuticals. The main patents currently on the market are also described in Section 5.

4. Microalgae and Cyanobacteria Exopolysaccharides: Cosmetic Properties and Potential Uses

The use of algae-derived metabolites in cosmetics is currently increasing, driven by the wide variety of biologically active compounds that can be obtained and the growing consumer awareness and preference for eco-friendly, natural ingredients [84].

As has been previously mentioned, the biological activities of exopolysaccharides from microalgae and cyanobacteria have been investigated for nutritional and pharmacological uses (mainly their anti-inflammatory, immunomodulatory, and antiviral activity). However, their uses in cosmetic and cosmeceutical formulations are recent. In addition to their potential as active ingredients, microalgae EPSs may be of interest in the cosmetic industry for use as thickeners and gelling agents.

Table 1. Activities of microalgal EPSs and their potential use in the cosmetic field.

Genus/Species/Strain	EPS	Type of Study	Activity	Reference	Potential Cosmetic Use
Spirulina platensis	Calcium spirulan (Rha, Rib, Man, Fru, Gal, Xyl, Glu, GlcA, GalA, sulfate, and calcium)	In vitro	Antiviral: replication inhibition of several enveloped viruses	[76]	Antimicrobial (active ingredient/preservative)
Porphyridium sp.	Main sugars: Xyl, Glc, and Gal; glycoproteins; and sulfate	In vitro In vivo (human subjects)	In vitro: inhibition migration of polymorphonuclear leucocytes In vivo: inhibition induced cutaneous erythema	[85]	Anti-inflammatory
Nostoc flagelliforme	Nostoflan (Glc, Gal, Xyl, and Man)	In vitro	Potent anti-herpes simplex virus type 1 (HSV-1) activity	[86]	Antimicrobial (active ingredient/preservative)
Arthrospira platensis	Calcium spirulan	In vitro	Antiviral: inhibition of orthopoxvirus and other enveloped viruses	[77]	Antimicrobial (active ingredient/preservative)
Rhodella reticulata	Deproteinized EPSs	In vitro	Antioxidant	[87]	Antioxidant
Arthrospira platensis	Methanolic and aqueous EPS extracts (composition not reported)	In vitro	Antibacterial Antioxidant	[88]	Antibacterial (preservative) Antioxidant
Porphyridium cruentum	Main sugars: Xyl, Gal, and Glu	In vitro	Inhibition of collagenase, elastase, and hyaluronidase activity	[89]	Anti-aging
Nostoc flagelliforme	Glc (41.2%), Gal (21.1%), Man (21.0%), Fru (2.5%), Rib (3.6%), Xyl (1.7%), Ara (0.6%), Rha (3.0%), Fuc (0.9%), and GlcA (4.3%)	Cosmetic formulation: rheological test	Strong emulsion-stabilizing capacity	[90]	Emulsifier and stabilizer
Porphyridium cruentum	Carbohydrates and uronic acids; Main sugars: Gal, Glu, and Ara; Minor sugars: Man, Fuc, Xyl, and Rha	In vitro Rheological test	Antibacterial and antiviral activities High viscosity values at low shear rates	[91]	Antibacterial (preservative) Rheological agent
Nostoc carneum	Xyl, Glu, and uronic acids	In vitro Rheological test	Antioxidant Pseudoplastic fluid behavior	[92]	Antioxidant Gelling and emulsifier agent
Cyanobacterium aponinum	GalA/Fuc/3-OMe-GalA/Glc/Ara/Gal/Man/Rha in a molar ratio of 24:24:17:16:10:4:3:2	In vitro	Production of immunosuppressive cytokine IL-10	[93]	Anti-inflammatory
Graesiella sp.	Carbohydrate (52%), uronic acids (23%), ester sulfate (11%), and protein (12%); Carbohydrate fraction: Glc, Gal, Man, Fuc, Rha, Xyl, Ara, and Rib	In vitro	Scavenging activity	[94]	Antioxidant
Anabaena sp. CCC 745	Heteropolysaccharide composed of Glc, Xyl, Rha, and GlcA	In vitro Rheological test	Antioxidant Pseudoplastic fluid behavior	[55]	Antioxidant Rheological agent
Anabaena sp. CCC 746	Main monosaccharides: Glc, Xyl, and GlcA	In vitro Rheological test	Antioxidant scavenging activity Pseudoplastic fluid behavior	[95]	Antioxidant Rheological agent
Phormidium sp. ETS05	Xyl, Rha, Glc, Man, Ara, GlcN, GalA, and GlcA	In vitro	Anti-inflammatory activity	[96]	Anti-inflammatory
Porphyridium cruentum	Glc and carboxylic acid compounds	In vitro	Immune response against vibriosis	[97]	Antibacterial (preservative)
Tetraselmis suecica	Glc (23–37%), GlcA (20–25%), Man (2–36%), Gal (3–25%), galactoryranoside (5–27%), GalA, (0.1–3%), Ara (5%), Xyl (0.3–3%) Rib, Rha, and Fuc (1%)	In vitro	Antioxidant	[98]	Antioxidant
Porphyridium sordidum	Gal (~40%), Xyl (~30%) and Glu (~30%)	In vitro	Plant antifungal activity	[99]	Antifungal (preservative)
Nostoc sp.	α-Rib, α-Glc, α-LAra, α-Xyl, α-LRha, β-Man, β-Gal, GalA, and β-LFuc	In vitro	Fibroblast proliferation and migration	[100]	Wound healing Skin barrier repair
Scenedesmus acutus	Octa-saccharides	In vitro	Antioxidant	[101]	Antioxidant
Chlorella sorokiniana, Chlorella sp., Picochlorum sp.	Sulfated EPSs	In vitro	Antioxidant	[80]	Antioxidant
Nostoc cf. linckia	Dominant neutral saccharides, Glu, Gal, Xyl, and Man, and minor amounts of Rha, Fuc, and Ara	In vitro	Antioxidant	[102]	Antioxidant
Gloeocapsa gelatinosa	Man (~22%), Xyl (~9%), Ara (~10%) GalA (~7%), and GlcA (~8%), Rha (~12%), and Fuc (~40%)	In vitro	Free radicals’ scavenger Antioxidant Metal chelating activity	[103]	Antioxidant Chelating agent
Botryococcus braunii	HMW heteropolysaccharides: uronic acid (7.43–8.83%), protein (2.30–4.04%), and sulfate groups (1.52–1.95%). Gal (52.34–54.12%), Glc (34.60–35.53%), Ara (9.41–10.32%), and Fuc (1.80–1.99%)	In vitro	Antioxidant	[104]	Antioxidant
Porphyridium cruentum (CCALA415)	Neutral monosaccharides: D- and L-Gal, D-Glc, D-Xyl, D-GlcA, and sulfate groups	In vitro	Anti-inflammatory Antioxidant Enhancement of wound closure	[23]	Anti-inflammatory Antioxidant Skin barrier repair
Porphyridium cruentum, Chrysotila dentata, Pavlova sp., Diacronema ennorea, Glossomastix sp., Phaeodactylum tricornutum, Synechococcus sp.	P. cruentum EPS: Gal (44%), Xyl (39%), and Glc (14%). C. dentata, Pavlova sp., D. ennorea, P. tricornutum, and Synechococcus sp. EPS: Gal (26–38%) and Ara/Xyl (36%/17%), Rha/Glc (47%/11%), Rha/Ara (33%/17%), Glc/Ara (42%/13%), and Glc/Fuc (38%/24%). Glossomastix sp. EPS Fuc/Rha/GalA (40%/31%/21%)	In vitro	MMP-1 inhibition Stimulation of collagen production in cell lines CDD-1059Sk and CDD-1090Sk	[105]	Stimulation of skin collagen production (preventing ageing)
Auxenochlorella protothecoides	Gal (42.41%) and Rha (35.29%)	In vitro	Inhibition of the inflammatory response in lipopolysaccharide-induced RAW264.7 cells	[31]	Anti-inflammatory
Halamphora sp.	Xyl (40.55%), L-Gal (13.25%), D-Gal (13.00%), Glc (9.95%), and ribitol (9.82%)	In vitro	Antimicrobial activity	[106]	Antimicrobial (preservative)
Glossomastix sp.	Rha and Fuc as major monosaccharides and Gal, GalA, and GlcA as minor monosaccharides	Rheological test	Anti-settling stabilizers	[71]	Rheological agent
Arthrospira maxima	Heteropolymer, with Man, Xyl, and GlcA	In vitro	Antibacterial activity Antioxidant	[107]	Antibacterial (preservative) Antioxidant

Ara, arabinose; Fuc, fucose; Fru, fructose; Gal, galactose; GalA, galacturonic acid; Glc, glucose; GlcA, glucuronic acid; GlcN, glucosamine; Man, mannose; Rha, rhamnose; Rib, ribose; Xyl, xylose.

shows a short description of the composition and the properties of microalgae EPSs and their potential use in the cosmetic field, organized chronologically.

The first studies published in the 1990s emphasized the antiviral properties of exopolysaccharides. Two studies related to calcium spirulan (Ca-SP) obtained from Spirulina platensis (currently Arthrospira platensis) demonstrated that Ca-SP was able to inhibit the replication of several enveloped viruses, including herpes simplex virus type 1, human cytomegalovirus, measles virus, mumps virus, influenza A virus, and HIV-1. Ca-SP was found to selectively inhibit virus penetration into host cells. Its antiviral effect was suggested to be related to the retention of molecular conformation by chelating calcium ions with sulfate groups [76,77]. Although its antiviral activity is not specific to cosmetic formulations, this activity suggests that Arthrospira EPSs could exert antimicrobial properties, which was confirmed in subsequent studies. Thus, later studies showed that Arthrospira platensis EPS methanolic and aqueous extracts (exact composition not reported) exerted antibacterial activities on both Gram (+) and Gram (−) organisms, highlighting that methanolic extracts showed the broadest activity spectrum, resulting in effective inhibition against three microbial strains, Pseudomonas aeruginosa, Salmonella typhimurium, and Micrococcus luteus. And the aqueous extracts were only effective against two strains, Staphylococcus epidermis and S. typhimurium [88]. Recent investigations showed that Arthrospira maxima also exerts antibacterial activity against several strains, such as Bacillus subtilis (MIC: 0.6 ± 0.05 mg/mL), Bacillus cereus (MIC: 1 ± 0.01 mg/mL), Escherichia coli (MIC: 0.8 ± 0.01 mg/mL), and Klebsiella pneumonia (MIC: 0.8 ± 0.01 mg/mL). This strain also showed antioxidant activity (DPPH radical scavenging assay) and also demonstrated interesting emulsifying properties [107].

Other microalgal and cyanobacterial EPSs showed antimicrobial activities. Nostoflan (Glc, Gal, Xyl, and Man rich), from Nostoc flagelliforme, showed potent anti-herpes simplex virus type 1 (HSV-1) activity and also antiviral activities against HSV-2, human cytomegalovirus, and influenza A virus, with the advantage that it does not show antithrombin activity, unlike other sulfated polysaccharides [86]. EPSs from the genus Porphyridium also showed antibacterial and antiviral activities [91,97]; some of them also have antifungal activity, such as Porphyridium sordidum, characterized by a high content of Gal (~40%), Xyl (~30%), and Glu (~30%) [99]. Diatom Halamphora sp. EPSs, despite showing low activity against Gram (+) bacteria, demonstrated moderate activity against Gram (−) bacteria, such as Escherichia coli [106].

These antimicrobial activities are of great interest, as the cosmetic industry seeks natural antimicrobial preservatives to mitigate and prevent adverse reactions caused by synthetic ones. On the other hand, they may also be of interest as active ingredients in the treatment of acne. Antifungal activity could also be relevant for the development of natural cosmetic preservatives. Therefore, additional studies are needed to determine the minimum inhibitory concentration to evaluate preservative effectiveness, as well as skin compatibility tests to evaluate the use of microalgae EPSs in cosmetics.

The antioxidant capacity of EPSs has also been demonstrated in several studies. For instance, the aforementioned EPS methanolic extracts from Arthrospira platensis showed high antioxidant activity [88]. Chen et al. compared a crude ESP and deproteinized an EPS from Rhodella reticulata, finding that both of them exerted free radical scavenging and antioxidant activity in a dose-dependent manner, but the crude EPS exhibited higher free radical scavenging capacity and better antioxidant activity than the deproteinized EPS. In any case, the role of proteins in antioxidant activity is not clearly explained. In addition, the superoxide anion radical scavenging ability of EPS samples was significantly higher compared to the standard antioxidant (α-tocopherol) [87]. EPSs from thermophilic microalgae have also been studied to evaluate their antioxidant capacity. For example, aqueous extracellular polysaccharides from the thermophilic microalgae Graesiella sp. was shown to exert moderate scavenging activity [94].

EPSs from Nostoc species and strains also show antioxidant activity. For instance, the Nostoc carneum ESP was shown to possess antioxidant activity but also showed non-Newtonian pseudoplastic behavior, or a shear thinning property, in aqueous solutions, which could be of interest in the cosmetic industry for use as gelling and emulsifier agents (allowing products like lotions to flow through a pump and spread easily on the skin) [92]. Nostoc cf. linckia also shows antioxidant properties, demonstrating that the crude polymer and its purified fractions, as well as deproteinized EPSs, possess higher antioxidant capacity than other similar polysaccharides from Nostoc flagelliforme and N. commune [102].

EPSs from Anabaena sp. CCC 745 and Anabaena sp. CCC 746 exhibit significant antioxidant and scavenging activity [55,95]. EPSs from Tetraselmis suecica (Kylin) Butcher also show antioxidant activity; this is suggested to be related to the percentage of galacturonic and glucuronic acids present in the constitution of an EPS of T. suecica [98]. Octa-saccharides from Scenedesmus acutus also present scavenging activity [101], and EPSs from the thermophilic Gloeocapsa gelatinosa demonstrate a high amount of activity as free radical scavengers, as well as metal chelating activity, with both activities being of interest in the field of cosmetics [103].

Other studies on the crude EPS from Botryococcus braunii, a microalga widely studied for its biofuel production potential, showed its strong antioxidant activity, so it can be considered a good source of antioxidants for the food and cosmetic industry [104]. Mousavian et al. investigated sulfated EPSs from the marine green microalgae Chlorella sorokiniana, Chlorella sp., and Picochlorum sp., finding that sulfated EPSs with a higher sulfate/sugar ratio presented potent ABTS radical scavenging activity [80].

Other studies focused on reversing the activity of some enzymes involved in aging. Porphyridium cruentum EPSs were shown to inhibit the activity of enzymes like collagenase, elastase, and hyaluronidase, which play roles in dermal extracellular matrix degradation and aging. This inhibition suggests a potential role for Porphyridium cruentum SPs in developing cosmetic products with anti-aging and regenerative effects [89].

Studies have also been carried out on the applications of a mixture of the Haslea ostrearia EPS and marennine (a blue pigment obtained from this marine diatom) to improve skin hydration and prevent aging, although the composition of the EPS is not shown in these works [108].

In addition to the aforementioned antioxidant activities, EPSs from the genus Porphyridium, with acidic characteristics, may have potential applications in cosmetics as an inhibitor hyaluronidase and anti-allergic and anti-inflammatory agents [85] and have antioxidant activity and anti-inflammatory properties [91]. For example, Porphyridium cruentum (CCALA415) EPSs showed anti-inflammatory activity comparable to that of ibuprofen and helped tissue regeneration in in vitro and cell-based assays [23].

Other microalgal strains can also exert anti-inflammatory properties. An EPS from Cyanobacterium aponinum, the dominating member of the Blue Lagoon’s microbial ecosystem, was able to stimulate DCs to produce vast amounts of the immunosuppressive cytokine IL-10 [93]. It should be considered that this treatment was carried out using a lyophilized-conditioned culture medium; therefore, the observed effects may be partly attributable to cytokines, diacylglycerols, and other compounds released by the cultured cyanobacteria. An EPS from Phormidium sp. ETS05, the most abundant cyanobacterium of therapeutic Euganean thermal muds, exerted anti-inflammatory and pro-resolution activities in chemical and injury-induced zebrafish inflammation models [96]. And the Auxenochlorella protothecoides EPS, rich in Gal (42.41%) and Rha (35.29%), inhibited the inflammatory response in lipopolysaccharide-induced RAW264.7 cells by quenching inflammatory factor levels, such as ROS, iNOS, TNF-α, and IL-6 [31].

In order to investigate their potential anti-aging properties, Toucheteau et al. studied several microalgal strains, such as Porphyridium cruentum, Chrysotila dentata, Pavlova sp., Diacronema ennorea, Glossomastix sp., Phaeodactylum tricornutum, Synechococcus sp. EPSs were isolated and depolymerized and tested, showing that native microalgae EPSs were able to inhibit 27% of human matrix metalloproteinase-1 (MMP-1) activity, while the depolymerized forms were able to enhance collagen production by two different human fibroblast lines. The results also show that MMP-1 inhibition was strongly correlated with the sulfate group content of the EPS, whereas collagen production by fibroblasts was mostly related to their proportion of LMW polysaccharides (<10 kDa) [105].

As preventing and slowing aging is one of the goals of cosmeceuticals and skin care products, EPSs seem to be a suitable ingredient, combined with other natural bioactive substances, in the formulation of specific dermocosmetics focused on antioxidant and anti-ROS bioactivities.

The wound healing properties of certain EPSs are also of interest in the formulation of cosmeceuticals aimed at enhancing skin barrier repair and promoting epithelialization. Thus, Álvarez et al. investigated two Nostoc sp. strains (PCC7936 and PCC7413) to be used as a biomaterial for new wound dressings, finding that both strains could promote fibroblast migration and proliferation, with greater activity in PCC7936 (in vitro assay) [100]. Vázquez-Ayala et al. designed wound dressings loaded with metformin for diabetic foot healing, combining an EPS from Porphyridium purpureum with fucoidan and chitosan. Interestingly, metformin-loaded chitosan sponges regenerated skin tissue after 21 days of treatment, highlighting the healing rate achieved when exopolysaccharides were added to promote tissue regeneration. Additionally, the sponge composites exerted antibacterial activity and were neither cytotoxic or hemolytic [109].

In any case, as frequently occurs in cosmetics, it is necessary to specify whether the effects on the skin are due to the use of EPSs as active ingredients or to the synergy between the different bioactive compounds (proteins, polyphenols, etc.) that accompany these EPSs and even the vehicles or other functional ingredients used in the cosmetic formulation.

Other properties of microalgal and cyanobacterial EPSs may have potential applications in cosmetics, as they can be used as emulsifiers and stabilizers. The Nostoc flagelliforme EPS demonstrated strong emulsion-stabilizing capacity [90], and the Porphyridium cruentum EPS in aqueous solutions with 2% (w/v) showed high viscosity values at low shear rates [91]. The Nostoc carneum EPS, rich in Xyl, Glu, and uronic acid, presented pseudoplastic fluid behavior [92]. Anabaena sp. CCC 746 and Anabaena sp. CCC 746 both presented pseudoplastic fluid behavior, in addition to the aforementioned scavenging activity [55,95]. Finally, the anti-settling stabilizer properties of the Glossomastix sp. EPS deserve to be cited, as they may have potential use as rheological agents in the cosmetic formulation of gels and creams [71].

5. Patents Claiming the Use of Microalgal and Cyanobacterial EPSs in Skin Care

Different patents claiming the incorporation of microalgal and cyanobacterial EPSs for non-therapeutic formulations in skin care to enhance the health and appearance or texture of skin have been registered [110,111,112,113]. Most of them are designed for topical application, but there are also ones for oral or injection into skin tissue [111]. Some examples are shown in Table 2. The products are not always obtained from pure cultures. Also, exopolysaccharides obtained by fermentation are isolated from marine bacteria found in a cyanobacterial population on a kopara microbial mat [114].

Polysaccharides can be precipitated by adding compounds such as cetylpyridinium chloride, isopropanol, ethanol, or methanol to an aqueous solution containing the polysaccharide. Membrane filtration can be used to concentrate polysaccharides and remove salts. Polysaccharides can also be dialyzed to remove excess salt and other small molecules. Anionic polysaccharides can be purified by anion exchange chromatography [110,111] or by immobilized metal affinity chromatography [115].

Polysaccharides can be treated with proteases to degrade attached contaminating proteins, either covalently or noncovalently, and after digestion, the polysaccharide is purified from residual proteins, peptide fragments, and amino acids. Heat treatment can also be used to eliminate proteins, amino acids, peptides, and salts [111]. In some cases, heterotrophically produced microalgal polysaccharides or extracts have pigments as a by-product of the fermentation process. In some cases, discoloration is used to remove undesirable coloration and pigments destined for cosmetic or nutraceutical formulation. Among the methods are bleaching; solvent extraction; adsorption; enzyme treatment; and washing with acid, alcohol, or a salt solution [111]. In other cases, simplicity is preferred, and low-cost obtention of the product allows for a greater presence of glycoproteins rich in hydroxyproline, an important component of collagen [115].

The obtained polysaccharides may have any level of sulfation [111], with molecular weights in the range of 30–100 kDa [116], and they can be structurally modified both enzymatically and chemically, and modifications include sulfation, phosphorylation, methylation, O-acetylation, fatty acylation, amino N-acetylation, N-sulfation, branching, and carboxyl lactonization [111]. Depolymerization has been also explored after pretreatment by high pressure (2.7 kbar) and freeze-drying, i.e., by acid hydrolysis onto cationic resins (Amberlityst^® 15 DRY) in batch or in continuous mode to increase the production of collagen and/or hyaluronic acid in order to delay the effects of skin aging [116].

Different formulations in cosmetic products add exopolysaccharides, wet, dialyzed or non-dialyzed [117], or dried by lyophilization or dried to form a film by heating the microalgal EPS at 135–160 °C [112].

The EPS can be added to the cosmetic at 0.1 to 10% (w/w) of the cream formulation [117]. Higher content has also been proposed, i.e., ref. [118] provides a composition comprising 2–60 wt% of a sulfated polysaccharide for moisturizing the skin. The final composition has to be sterile or substantially free of endotoxins and/or proteins [111]. Products may contain one or more microalgal polysaccharides, purified or semi-purified [110,111]. In some cases, secreted polysaccharides and also polysaccharides present in the cell wall, either crude, purified, or semi-purified, have been used to obtain nutraceutical, cosmeceutical, and pharmaceutical compositions [110,111].

The mixture of microalgal biomass and polysaccharides has been proposed; thus, microalgal extracts can include microalgal oil, proteins, lipids, carbohydrates, phospholipids, polysaccharides, macromolecules, minerals, cell walls, trace elements, carotenoids, and sterols [111], as well as a combination of microalgal bio-products from different species to produce a product of interest. Another patent claimed the production of a water-soluble carotenoid from Haematococcus pluvialis or a capsular EPA from Parachlorella sp. and formulated compositions containing the carotenoid as sunscreen and others containing the EPS as moisturizing cream [119].

EPSs are formulated with at least one excipient suitable for topical administration with a carrier, pigments, emulsifiers, fillers, preservatives, antioxidants, and optionally odor absorbers and fragrances [110,111,118]. These polysaccharides can also confer some of these actions, i.e., of forming a gel and swelling with water [110,113], and can be used as enhancers of rheological and sensory characteristics, providing products with greater spread ability, consistency, less residual grease sensation, shine, drying speed, among others [117].

Different formats are available, such as gel, oil, lotion, spray, cream, emulsion, and ointments for facial care and makeup, lip care, hair care, and tooth and mouth washes [111,119]. Other topical formulations include impregnated bandages, biodegradable microcapsules, polymers, and artificial skin. However, the following most valuable properties could be of interest to formulate cosmeceuticals, with interesting biological activities: anti-aging, healing, anti-acne, oil-reducing or cellulite properties; stimulating elastin synthesis in the skin, or functioning as an anti-inflammatory agent, to improve barrier function of the skin and/or to hydrate the skin [111,118]; anti-inflammatory properties [111]; reducing the effects of ultraviolet radiation [111] to aid in wrinkle reduction [113] and anti-aging [89], which can be due to inhibition of elastase, by chelating the calcium necessary for activation of the enzyme; and collagenase [89,111], or exerting antioxidant activity [22,120]. In addition, by combining a growth factor and a microalgal culture supernatant, a synergistic effect was observed to increase proliferation of fibroblasts for the treatment of skin aging, photoaging, and cutaneous senescence [115], to increase the production of collagen and/or hyaluronic acid, and to delay the effects of skin aging [116]. In other embodiments, the composition further comprises hyaluronic acid or another agent suitable or desirable for the treatment of skin [111]. In addition, the EPS could be incorporated in nutraceuticals, i.e., as an antioxidant based on the confirmed potential for protecting food from oxidation [121].

Table 2 shows some examples of patents, including a short explanation of the production and/or main composition.

Based on previous research and development, cosmetic applications have emerged that have been developed by cosmetic raw material suppliers or the brands themselves. Some examples are described below.

Silidine^® is a mix of trace elements and a small EPS from Porphyridium purpureum, obtained by applying an oxidative stress to microalgae by closing the air tightly in a culture batch of 1 m³. Silidine^® claims to fight against redness and heavy legs syndrome (https://www.greentech.fr/).

Epsiline^® is a modified Porphyridium purpureum EPS sold as a melanin booster. It is obtained from an optimized cultivation process, adjusting parameters in terms of media composition, quantity of light, and injection of carbon dioxide to reduce by one-third the time it takes to obtain the EPS in photobioreactors, followed by a hydrolysis that allows for the creation of a new “medium molecular weight” EPS (https://www.greentech.fr/).

Other examples are AlgoSource (https://algosource.com/), which produces dry extracts from Porphyridium cruentum with a very high concentration of the EPS, and Alguronic acid^TM by Algenist^® (https://www.algenist.com/), obtained from Parachlorella kessleri or Parachlorella beijerinckii strains, which claims anti-aging skincare properties.

Table 2. Examples of patents claiming the utilization of microalgal EPSs for the improvement of skin health and appearance.

Microalgae or Cyanobacteria	EPS Preparation and Main Composition	Application/Potential Use	Applicant/Patent Number	Reference
Arthrospira spirulina or Spirulina platensis and Spirulina maxima	Sulfated polysaccharide comprising 2% to 60% by weight, based on the total weight of the polymer, of a rhamnose unit	Cosmetic skin moisturizing product compatible with cutaneous tissues (skin and scalp). Compositions with the appearance of white or colored compositions in any form, such as ointment, milk, lotion, serum, paste, foam, aerosol, or stick.	L’Oréal SA, FR2982152A1	[118]
Several microalgal and cyanobacteria strains; for example, Chlorella sp., Dunaliella sp., Tetraselmis sp., Anabaena sp, Aphanizomenon sp., Arthrospira sp., Nostoc sp., Isochrysis sp., Phaeodactylum sp., Skeletonema sp., Thalassiosira sp., Nannochloropsis sp., Porphyridium sp., among others	An EPS of wet, non-dialyzed, and non-lyophilized origin, added at 0.1–10% (wt) to the cream formulation. EPS composition not mentioned	Cosmetic formulation for topical use on human hair, skin, mucous membranes, and nails. Microalgal EPS as an enhancer of rheology, stability, and sensory properties. Base cream for the addition of microalgal extracts as antioxidant, surfactant, emulsifier, emollient emulsifier, preservative, and antimicrobial.	Univ Fed Do Parana, BR102012004631A2	[117]
Genus Parachlorella	(i) Isolation and precipitation with alcohol, (ii) drying and forming a film, and (iii) contacting with water and forming a gel and air drying. EPS average size of between 0.1 and 400 microns. EPS composition not mentioned.	Skin care compositions for wrinkle reduction and for improving the health and appearance of skin	Solazyme Inc. Algenist Brands Inc., US9095733B2	[110]
Parachlorella kessleri, Parachlorella beijerinckii, or Chlorella sorokiniana	EPS composition: 15–55 mole percent of rhamnose, 3–30 percent of moles of xylose, 1–25 mole percent of mannose, 1–45 mole percent of galactose, 0.5–10 mole percent of glucose, and 0.1–15 mole percent of glucuronic acid	Skin care products to deliver cosmeceutical ingredients, such as carotenoids, polyunsaturated fatty acids, moisturizing polysaccharides, superoxide dismutase, etc.	Algenist Holdings Inc., ES2718275T3	[111]
EPSs from PUFA-producing microalgae fermentation waste liquid of Schizochytrium sp., Cryptidnodinium koushii, Crypthecodinium cohnii SD401, or Nannochloropsis sp.	Disc centrifuge separation, micro-filtration in ceramic membrane, ultrafiltration (30 kDa) to concentrate (50–70% solids), and vacuum-drying (moisture 1%). 71–73% EPS, 9–11% peptide and protein, 3–4% monosaccharide content	Formulation of EPS as wall material in emulsions of a DHA, Tween 80, and gelatin solution protected against oxidation and spray-dried in microcapsules	Qingdao Institute of Bioenergy and Bioprocess Technology of CAS, CN108559006A	[32]
Parachlorella, Porphyridium, Chaetoceros, Chlorella, Dunaliella, Isochrysis, Phaeodactylum, Tetraselmis, Botryococcus, Cholorococcum, Hormotilopsis, Neochloris, Ochromonas, Gyrodinium, Ellipsoidion, Rhodella, Gymnodinium, Spirulina, Cochlodinium, Nostoc, Cyanospira, Cyanothece, Tetraselmis, Chlamydomonas, Dysmorphococcus, Anabaena, Palmella, Anacystis, Phormidium, Anabaenopsis, Aphanocapsa, Cylindrotheca, Navicula, Gloeocapsa, Phaeocystis, Leptolyngbya, Symploca, Synechocystis, Stauroneis, and Achnanthes, preferably Parachlorella kessleri.	Isolation of microalgal EPS from the culture medium, drying at 40–180 °C to form a film insoluble in water, homogenizing the film into particles, formulating the particles into a non-aqueous material, oil phase of an oil-in-water emulsion, and generating 0.1–50 microns particles. EPS composition not mentioned.	Topical personal care products or by injection into skin or a skin tissue and wrinkle reduction	TerraVia Holdings Inc., EP3398606A1	[112]
Parachlorella sp.	Capsular exopolysaccharide obtained by separating the exopolysaccharide producing microalgal cells from the culture medium, heating the microalgal cells to release the cellular capsule, and removing the insoluble solids to produce an aqueous solution containing the EPS. EPS composition not mentioned.	Vehicle for personal care products	KUEHNLE AGROSYSTEMS Inc., US20200232003A1	[119]
Glossomastix sp, Chrysotila dentata, Pavlova sp., Phaeodactylum tricornutum, and Synechococcus sp.	New depolymerized exopolysaccharides (30–100 kDa) and method of obtaining the EPIS, consisting of the following: pretreatment by high pressure (2.7 kbar), freeze-drying, and depolymerization by acid hydrolysis onto cationic resins (Amberlityst® 15 DRY) in batch or in continuous mode. EPS composition not mentioned.	Product to increase the production of collagen and/or hyaluronic acid to delay the effects of skin aging	Centre National de la Recherche Scientifique CNRS, Univ. Nantes, La Rochelle Univ., Sorbonne Univ., Univ. Clermont Auvergne, Univ. Rouen Normandie, FR2102020	[116]
Chlorella sp.	Precipitation, centrifugation, purification, and freeze-drying 131.79 kDa EPS; mainly comprises xylose, mannose, and ribose	Antioxidant activity (DPPH, hydroxyl, ABTS radicals, and superoxide anions)	Xiangtan University, CN110818814A	[22]
Cyanobacteria of the genus Synechococcus CCMP 1333, Synechococcus PCC 7002, and Cyanothece Miami BG 043511	EPS isolation, drying milling to a size of between 400 microns and 0.1 microns to prepare exopolysaccharide particles, and annealing the EPS particles. EPS composition not mentioned.	Topical personal care products, cosmetics for improving the health and appearance of skin, and wrinkle reduction composition	Heliobiosys, Inc., US20240358628A1	[113]
Cyanobacterium Spirulina platensis	Enhancer of rheology, stability, and sensory properties and antioxidant. EPS freeze-dried or wet, dialyzed or non-dialyzed. A total of 0.1–10% (wt) of the cream formulation. EPS composition not mentioned.	Novel products with antioxidant, anti-aging, healing, oil-reducing, antiacne, rheological, and sensory properties	Univ Fed Do Parana, BRPI1004637A2	[120]
Cell wall-less microalgal strain Chlorophyceae class or Volvocales order, Chlamydomonadaceae family, and Chlamydomonas reinhardtii	Concentration by lyophilization or by tangential flow filtration IMAC-enriched microalgal culture supernatant comprises between 1 μg/L and 0.1 g/L of proteins and between 0.001 mg/L and 10 g/L of carbohydrates	Cosmetic or cosmeceutical composition for wound healing or skin damage repair, increased proliferation of fibroblasts for the treatment of skin aging, photoaging, and cutaneous senescence	Greenaltech, S.L Gat Biosciencies SL, US12268772B2	[115]

Table 2. Examples of patents claiming the utilization of microalgal EPSs for the improvement of skin health and appearance.

Microalgae or Cyanobacteria	EPS Preparation and Main Composition	Application/Potential Use	Applicant/Patent Number	Reference
Arthrospira spirulina or Spirulina platensis and Spirulina maxima	Sulfated polysaccharide comprising 2% to 60% by weight, based on the total weight of the polymer, of a rhamnose unit	Cosmetic skin moisturizing product compatible with cutaneous tissues (skin and scalp). Compositions with the appearance of white or colored compositions in any form, such as ointment, milk, lotion, serum, paste, foam, aerosol, or stick.	L’Oréal SA, FR2982152A1	[118]
Several microalgal and cyanobacteria strains; for example, Chlorella sp., Dunaliella sp., Tetraselmis sp., Anabaena sp, Aphanizomenon sp., Arthrospira sp., Nostoc sp., Isochrysis sp., Phaeodactylum sp., Skeletonema sp., Thalassiosira sp., Nannochloropsis sp., Porphyridium sp., among others	An EPS of wet, non-dialyzed, and non-lyophilized origin, added at 0.1–10% (wt) to the cream formulation. EPS composition not mentioned	Cosmetic formulation for topical use on human hair, skin, mucous membranes, and nails. Microalgal EPS as an enhancer of rheology, stability, and sensory properties. Base cream for the addition of microalgal extracts as antioxidant, surfactant, emulsifier, emollient emulsifier, preservative, and antimicrobial.	Univ Fed Do Parana, BR102012004631A2	[117]
Genus Parachlorella	(i) Isolation and precipitation with alcohol, (ii) drying and forming a film, and (iii) contacting with water and forming a gel and air drying. EPS average size of between 0.1 and 400 microns. EPS composition not mentioned.	Skin care compositions for wrinkle reduction and for improving the health and appearance of skin	Solazyme Inc. Algenist Brands Inc., US9095733B2	[110]
Parachlorella kessleri, Parachlorella beijerinckii, or Chlorella sorokiniana	EPS composition: 15–55 mole percent of rhamnose, 3–30 percent of moles of xylose, 1–25 mole percent of mannose, 1–45 mole percent of galactose, 0.5–10 mole percent of glucose, and 0.1–15 mole percent of glucuronic acid	Skin care products to deliver cosmeceutical ingredients, such as carotenoids, polyunsaturated fatty acids, moisturizing polysaccharides, superoxide dismutase, etc.	Algenist Holdings Inc., ES2718275T3	[111]
EPSs from PUFA-producing microalgae fermentation waste liquid of Schizochytrium sp., Cryptidnodinium koushii, Crypthecodinium cohnii SD401, or Nannochloropsis sp.	Disc centrifuge separation, micro-filtration in ceramic membrane, ultrafiltration (30 kDa) to concentrate (50–70% solids), and vacuum-drying (moisture 1%). 71–73% EPS, 9–11% peptide and protein, 3–4% monosaccharide content	Formulation of EPS as wall material in emulsions of a DHA, Tween 80, and gelatin solution protected against oxidation and spray-dried in microcapsules	Qingdao Institute of Bioenergy and Bioprocess Technology of CAS, CN108559006A	[32]
Parachlorella, Porphyridium, Chaetoceros, Chlorella, Dunaliella, Isochrysis, Phaeodactylum, Tetraselmis, Botryococcus, Cholorococcum, Hormotilopsis, Neochloris, Ochromonas, Gyrodinium, Ellipsoidion, Rhodella, Gymnodinium, Spirulina, Cochlodinium, Nostoc, Cyanospira, Cyanothece, Tetraselmis, Chlamydomonas, Dysmorphococcus, Anabaena, Palmella, Anacystis, Phormidium, Anabaenopsis, Aphanocapsa, Cylindrotheca, Navicula, Gloeocapsa, Phaeocystis, Leptolyngbya, Symploca, Synechocystis, Stauroneis, and Achnanthes, preferably Parachlorella kessleri.	Isolation of microalgal EPS from the culture medium, drying at 40–180 °C to form a film insoluble in water, homogenizing the film into particles, formulating the particles into a non-aqueous material, oil phase of an oil-in-water emulsion, and generating 0.1–50 microns particles. EPS composition not mentioned.	Topical personal care products or by injection into skin or a skin tissue and wrinkle reduction	TerraVia Holdings Inc., EP3398606A1	[112]
Parachlorella sp.	Capsular exopolysaccharide obtained by separating the exopolysaccharide producing microalgal cells from the culture medium, heating the microalgal cells to release the cellular capsule, and removing the insoluble solids to produce an aqueous solution containing the EPS. EPS composition not mentioned.	Vehicle for personal care products	KUEHNLE AGROSYSTEMS Inc., US20200232003A1	[119]
Glossomastix sp, Chrysotila dentata, Pavlova sp., Phaeodactylum tricornutum, and Synechococcus sp.	New depolymerized exopolysaccharides (30–100 kDa) and method of obtaining the EPIS, consisting of the following: pretreatment by high pressure (2.7 kbar), freeze-drying, and depolymerization by acid hydrolysis onto cationic resins (Amberlityst® 15 DRY) in batch or in continuous mode. EPS composition not mentioned.	Product to increase the production of collagen and/or hyaluronic acid to delay the effects of skin aging	Centre National de la Recherche Scientifique CNRS, Univ. Nantes, La Rochelle Univ., Sorbonne Univ., Univ. Clermont Auvergne, Univ. Rouen Normandie, FR2102020	[116]
Chlorella sp.	Precipitation, centrifugation, purification, and freeze-drying 131.79 kDa EPS; mainly comprises xylose, mannose, and ribose	Antioxidant activity (DPPH, hydroxyl, ABTS radicals, and superoxide anions)	Xiangtan University, CN110818814A	[22]
Cyanobacteria of the genus Synechococcus CCMP 1333, Synechococcus PCC 7002, and Cyanothece Miami BG 043511	EPS isolation, drying milling to a size of between 400 microns and 0.1 microns to prepare exopolysaccharide particles, and annealing the EPS particles. EPS composition not mentioned.	Topical personal care products, cosmetics for improving the health and appearance of skin, and wrinkle reduction composition	Heliobiosys, Inc., US20240358628A1	[113]
Cyanobacterium Spirulina platensis	Enhancer of rheology, stability, and sensory properties and antioxidant. EPS freeze-dried or wet, dialyzed or non-dialyzed. A total of 0.1–10% (wt) of the cream formulation. EPS composition not mentioned.	Novel products with antioxidant, anti-aging, healing, oil-reducing, antiacne, rheological, and sensory properties	Univ Fed Do Parana, BRPI1004637A2	[120]
Cell wall-less microalgal strain Chlorophyceae class or Volvocales order, Chlamydomonadaceae family, and Chlamydomonas reinhardtii	Concentration by lyophilization or by tangential flow filtration IMAC-enriched microalgal culture supernatant comprises between 1 μg/L and 0.1 g/L of proteins and between 0.001 mg/L and 10 g/L of carbohydrates	Cosmetic or cosmeceutical composition for wound healing or skin damage repair, increased proliferation of fibroblasts for the treatment of skin aging, photoaging, and cutaneous senescence	Greenaltech, S.L Gat Biosciencies SL, US12268772B2	[115]

6. Conclusions, Challenges, and Expected Developments

Exopolysaccharides from microalgae and cyanobacteria exhibit higher structural diversity, associated with different physicochemical and biological functionalities than those from terrestrial plants, fungi, and macroalgae, making them attractive for potential exploitation as commercial sources of new polysaccharides [122]. However, these EPSs remain underexplored for many potential applications, and the market is still developing [9,24].

The industrial applications may be based on their thickening, emulsifying, stabilizing, and film-forming properties. However, they are competitive with polysaccharides from macroalgae and terrestrial plants. Therefore, only special and niche applications requiring properties not fulfilled by the currently available products are promising [34,123], with the cosmetic field being one of the most promising. Even in this area, further research and developments are needed, and among the major challenges in this area of research, the following are mentioned: (i) bioprospection of strains and methodologies to discover reliable EPS producers of potential microorganisms and exploitable polysaccharides and understanding the metabolic pathway involved in their synthesis and release; (ii) engineering development to optimize their production cost, i.e., solar energy for cultivation and to cut the costs of downstream processes both on the laboratory and at the pilot or industrial scale; (iii) detailed physicochemical, structural, and biological characterizations to establish structure–activity relationships; (iv) development process for EPS production and also downstream processes adapted to the specific EPSs with high salts contents; and (v) development of novel applications and marketable products [1,11,15,21,24,29,122,124,125]. Another aspect that must also be considered is the safety and compatibility of cosmetic products that include EPSs in their composition through in vivo testing and clinical studies [126].

One of the major limitations for microalgal and cyanobacterial EPSs’ commercial exploitation is the high production costs [127]. EPS productivity and its concentration in a bacteria culture medium can be ten or more times higher than in a microalgae culture medium; therefore, the costs of recovery and purification from microalgae are still prohibitive [11]. Additionally, the recovery of EPSs that remains partially attached to the cells would require additional processing to recover the bound EPS without extracting intra-cellular compounds, and the economic reliability of this additional step should be considered [11]. Therefore, the industrial uses of microalgal EPSs are still limited to few niche markets with high selling prices, like cosmetics.

Regarding the cosmetic applications of EPSs, the reviewed articles showed interesting bioactivities, such as anti-inflammatory, antioxidant, and anti-aging properties, in addition to physicochemical properties that may be of interest to improve the technological aspects of cosmetic formulations, such as thickeners, emulsifiers, or preservatives.

Emphasis and further studies on the valorization of waste and underutilized streams to obtain high-value-added products in the cosmetics and cosmeceutical sectors may allow for a reduction in the use of synthetic additives, which are responsible for the presence of micropollutants in water. This could be a way to reuse microalgae cultivation waste while promoting green cosmetics.