Citation: Morilla, M.J.; Ghosal, K.; Romero, E.L. More Than Pigments: The Potential of Astaxanthin and Bacterioruberin-Based Nanomedicines. Pharmaceutics 2023, 15, 1828. https://doi.org/10.3390/ pharmaceutics15071828 Academic Editors: Ain Raal and Jyrki Heinämäki Received: 29 May 2023 Revised: 18 June 2023 Accepted: 19 June 2023 Published: 26 June 2023 Copyright: © 2023 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/). pharmaceutics Review More Than Pigments: The Potential of Astaxanthin and Bacterioruberin-Based Nanomedicines Maria Jose Morilla 1, *, Kajal Ghosal 2 and Eder Lilia Romero 1, * 1 Nanomedicine Research and Development Centre (NARD), Science and Technology Department, National University of Quilmes, Roque Saenz Peña 352, Bernal 1876, Argentina 2 Department of Pharmaceutical Technology, Jadavpur University, 188, Raja Subodh Chandra Mallick Rd., Jadavpur, Kolkata 700032, West Bengal, India; kajal.ghosal@gmail.com * Correspondence: jmorilla@unq.edu.ar (M.J.M.); elromero@unq.edu.ar (E.L.R.) Abstract: Carotenoids are natural products regulated by the food sector, currently used as feed dyes and as antioxidants in dietary supplements and composing functional foods for human consump- tion. Of the nearly one thousand carotenoids described to date, only retinoids, derived from beta carotene, have the status of a drug and are regulated by the pharmaceutical sector. In this review, we address a novel field: the transformation of xanthophylls, particularly the highly marketed astaxanthin and the practically unknown bacterioruberin, in therapeutic agents by altering their phar- macokinetics, biodistribution, and pharmacodynamics through their formulation as nanomedicines. The antioxidant activity of xanthophylls is mediated by routes different from those of the classical oral anti-inflammatory drugs such as corticosteroids and non-steroidal anti-inflammatory drugs (NSAIDs): remarkably, xanthophylls lack therapeutic activity but also lack toxicity. Formulated as nanomedicines, xanthophylls gain therapeutic activity by mechanisms other than increased bioavail- ability. Loaded into ad hoc tailored nanoparticles to protect their structure throughout storage and during gastrointestinal transit or skin penetration, xanthophylls can be targeted and delivered to se- lected inflamed cell groups, achieving a massive intracellular concentration after endocytosis of small doses of formulation. Most first reports showing the activities of oral and topical anti-inflammatory xanthophyll-based nanomedicines against chronic diseases such as inflammatory bowel disease, psori- asis, atopic dermatitis, and dry eye disease emerged between 2020 and 2023. Here we discuss in detail their preclinical performance, mostly targeted vesicular and polymeric nanoparticles, on cellular models and in vivo. The results, although preliminary, are auspicious enough to speculate upon their potential use for oral or topical administration in the treatment of chronic inflammatory diseases. Keywords: xanthophylls; inflammation; endocytosis; therapeutic; nanomedicines 1. Introduction Most of the intense antioxidant activity of dietary carotenoids comes from xantho- phylls, a particular type of carotenoid. Since many inflammatory diseases are connected to oxidation, dietary xanthophylls are acknowledged to prevent chronic diseases’ damages, as a function of the polarity of their terminal ends and their ability to locate in specific positions in lipid bilayers of cell organoids [1]. Xanthophylls are potent reactive oxygen and nitrogen species (ROS and RNS) quenchers, free-radical scavengers, and chain-breaking antioxidants; display potent anti-inflammatory activity; and constitute potential therapeu- tic agents [1]. After being absorbed, carotenoids biodistribute in predictable patterns in animal tissues. Xanthophylls such as lutein, (meso)-zeaxanthin, and zeaxanthin are highly concentrated in the macula lutea, where they prevent photochemical damage, delaying the development of age-related macular degeneration (a very common vision disorder in older adults) and glaucoma [2,3]. Their esterified forms act as UV absorbers and quenchers of singlet oxygen in the skin surface and subcutaneous tissue [4]. β-cryptoxanthin, lutein, and Pharmaceutics 2023, 15, 1828. https://doi.org/10.3390/pharmaceutics15071828 https://www.mdpi.com/journal/pharmaceutics