marine drugs Review Astaxanthin Delivery Systems for Skin Application: A Review Sarah Giovanna Montenegro Lima 1 , Marjorie Caroline Liberato Cavalcanti Freire 2 , Verônica da Silva Oliveira 1 , Carlo Solisio 3 , Attilio Converti 3 and Ádley Antonini Neves de Lima 1, *   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 Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affil- iations. Copyright: © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/). 1 Department of Pharmacy, Federal University of Rio Grande do Norte, Natal 59012-570, RN, Brazil; sarahmontenegrolima@gmail.com (S.G.M.L.); veronicasoliver47@gmail.com (V.d.S.O.) 2 Physics Institute of São Carlos, University of São Paulo, São Carlos 13566-590, SP, Brazil; marjorie_freire_@hotmail.com 3 Department of Civil, Chemical and Environment Engineering, Pole of Chemical Engineering, University of Genoa, I-16145 Genoa, Italy; solisio@unige.it (C.S.); converti@unige.it (A.C.) * Correspondence: adleyantonini@yahoo.com.br; Tel.: +55-(84)99928-8864 Abstract: Astaxanthin (AST) is a biomolecule known for its powerful antioxidant effect, which is considered of great importance in biochemical research and has great potential for application in cosmetics, as well as food products that are beneficial to human health and medicines. Unfortunately, its poor solubility in water, chemical instability, and low oral bioavailability make its applications in the cosmetic and pharmaceutical field a major challenge for the development of new products. To favor the search for alternatives to enhance and make possible the use of AST in formulations, this article aimed to review the scientific data on its application in delivery systems. The search was made in databases without time restriction, using keywords such as astaxanthin, delivery systems, skin, cosmetic, topical, and dermal. All delivery systems found, such as liposomes, particulate systems, inclusion complexes, emulsions, and films, presented peculiar advantages able to enhance AST properties, among which are stability, antioxidant potential, biological activities, and drug release. This survey showed that further studies are needed for the industrial development of new AST-containing cosmetics and topical formulations. Keywords: astaxanthin; delivery system; skin; cosmetics; drugs; drug release 1. Introduction Astaxanthin (AST) is a xanthophyll carotenoid that was first isolated from lobster by Kuhn and Sorensen and was commercialized as a pigmentation agent 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 C 40 H 52 0 4 (molecular mass 596.85 g·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 suggest promising applications in anti-aging products [5,6]. Regarding industrial applications, AST has been produced synthetically through cost- effective 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 hu- man 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). Mar. Drugs 2021, 19, 511. https://doi.org/10.3390/md19090511 https://www.mdpi.com/journal/marinedrugs