**1. Introduction**

Astaxanthin (AST) is a xanthophyll carotenoid that was first isolated from lobster by Kuhn and Sorensen and was commercialized as a pigmentation agen<sup>t</sup> for feed in the aquatic farm industry [1,2]. The AST, or 3,3-dihydroxy-β,β-carotene-4,4-dione, is a tetraterpene composed of 40 carbon atoms (Figure 1A), and its molecular formula is C40H5204 (molecular mass 596.85 <sup>g</sup>·mol−1) [3,4]. This reddish-orange pigment is solid at room temperature, is fat-soluble, and its log P (octanol/water partition) is 13.27 [4]. Furthermore, its chemical structure is composed of 13 conjugated double bonds that have the ability to neutralize free radicals, conferring the strong antioxidant activity of AST [3].

In recent years, AST has gained visibility and attracted attention for cosmetic and dermatological applications, thanks to its remarkable antioxidant properties, which are much stronger than those of tocopherol, and to its positive effects on skin health and protection against UV radiation, which may sugges<sup>t</sup> promising applications in anti-aging products [5,6].

Regarding industrial applications, AST has been produced synthetically through costeffective methods for large-scale production. However, the green microalgae *Haematococcus pluvialis*, due to its ability to accumulate AST at high levels, is the main source for human consumption, besides being the most promising source for its industrial biological production [1,7]. It can be found either in plants, animals, yeasts, or other algae species. Nowadays, it finds many applications in aquaculture, cosmetics, foods, nutraceuticals, and pharmaceuticals [1] (Figure 1B).

**Citation:** Lima, S.G.M.; Freire, M.C.L.C.; Oliveira, V.d.S.; Solisio, C.; Converti, A.; de Lima, Á.A.N. Astaxanthin Delivery Systems for Skin Application: A Review. *Mar. Drugs* **2021**, *19*, 511. https:// doi.org/10.3390/md19090511

Academic Editors: Masashi Hosokawa and Hayato Maeda

Received: 17 August 2021 Accepted: 1 September 2021 Published: 9 September 2021

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**Figure 1.** (**A**) Astaxanthin (AST) chemical structure. (**B**) The microalgae *Haematococcus pluvialis* is a promising source for AST industrial biological production and AST applications. Diagram created using BioRender.com (accessed on 17 August 2021).

In the foodstuffs field, AST has been widely used as a supplement and healthy functional food, due to its neuroprotective properties and its ability to scavenge the free radicals produced by physical exercise, improve human immunity, resist fatigue, delay aging and prevent a number of diseases that cause organ aging. In addition, it can be used as a food colorant and antioxidant, to enhance the sensory quality and nutritional values of foods [8]. Oral consumption of AST-containing supplements seems to have positive effects on the skin, such as facial skin rejuvenation [9], an increase in flap viability [10], protection against photoaging caused by UV irradiation [11,12], and improvements in fine lines/wrinkles, elasticity, moisture, age spot size and texture [13,14].

Topical AST application has been reported to have several skin health benefits, including antioxidant and anti-aging effects [13,15–19], protection against UV irradiation [16,20], anti-wrinkle [14,16,21], hydration [21], wound healing [22,23], anti-cancer properties [17], and anti-eczema effects [13,24].

However, the low bioavailability and solubility of AST limit its use in topical formulations. The development of delivery systems to improve AST's application for skin purposes is a promising way to develop new cosmetics and pharmaceutical products. With this goal in mind, this article aimed to review the delivery systems described in the literature for enhancing AST's properties, discuss the main results of the developed formulations and contribute to its applications in cosmetics and topical formulations.

#### **2. Astaxanthin Delivery Systems for Skin Application**

## *2.1. Vesicular Systems*
