Journal of Drug Delivery Science and Technology xxx (xxxx) xxx Please cite this article as: Marta Vinha Vieira, Journal of Drug Delivery Science and Technology, https://doi.org/10.1016/j.jddst.2020.102099 Available online 23 September 2020 1773-2247/© 2020 Elsevier B.V. All rights reserved. Research paper Preparation and characterization of Haematococcus pluvialis carotenoid-loaded PLGA nanocapsules in a gel system with antioxidant properties for topical application Marta Vinha Vieira a, *, 1 , Roberto Bianchini Derner b , Elenara Lemos-Senna a a Pharmaceutical Technology Laboratory, Department of Pharmaceutical Sciences, Federal University of Santa Catarina, Campus Trindade, Florian´ opolis, SC, 88040- 900, Brazil b Algae Cultivation Laboratory, Department of Aquaculture, Federal University of Santa Catarina, Servid˜ ao dos Coroas, Barra da Lagoa, Florian´ opolis, SC, 88061-600, Brazil A R T I C L E INFO Keywords: Haematococcus pluvialis Astaxanthin Antioxidant properties Polymeric nanocapsules Topical application ABSTRACT Haematococcus pluvialis is a green microalga that produces a considerable amount of carotenoids, mainly astaxanthin (ASTX), which is a powerful antioxidant compound. However, carotenoid compounds exhibit poor water solubility and high instability, which restrain their application in pharmaceutical products. Considering that, here we describe the encapsulation of Haematococcus pluvialis carotenoids into poly-lactide-co-glycolide nanocapsules (NC-ES Hp ), aiming to obtain an innovative topical product with antioxidant properties. Nano- capsules were prepared by the solvent displacement method and characterized according to size, zeta potential, total carotenoid content, and ASTX content. Poloxamer 407 was added to the colloidal dispersion to form a thermosensitive hydrogel (HG–NC–ES Hp ). Release studies demonstrated that the carotenoids were released from the gel system in a sustained way. In the DPPH scavenging assay, NC-ES Hp15 exhibited an antioxidant activity 9- fold higher than ascorbic acid. These results indicated that the hydrogel developed may be a promising formulation to provide prolonged protection of the skin against the photo-oxidation process. 1. Introduction Currently, there is growing interest in biologically active compounds derived from natural resources, particularly those that can effectively act on molecular targets involved in several diseases [1]. Carotenoids are the largest group of natural pigments, covering more than 700 substances already isolated and characterized. Such compounds are lipophilic molecules present in all photosynthetic organisms, which are produced as a secondary metabolite of plants, algae, fungi, and some bacteria [2]. In the latest decades, epidemiological studies have shown that diets with high doses of carotenoids are responsible for the pre- vention of many chronic diseases, such as diabetes mellitus, metabolic syndrome, cancer and cardiovascular disorders [3]. More recently, the benefcial effects of carotenoids have been explored by the healthcare and cosmetics industries, in which most of them have been associated with the strong antioxidant properties of these compounds [4]. Haematococcus pluvialis is a freshwater unicellular green microalga belonging to the Chlorophyceae class, which has received substantial attention from the scientifc and biotechnology communities as it is considered the most signifcant biological source of the carotenoid astaxanthin (ASTX) in nature [5,6]. Under extreme environmental conditions, such as high-intensity light or oligotrophic circumstances, this species undergoes morphological and biochemical modifcations, including an intense biosynthesis of that carotenoid, which may reach up to 4.0% of the cell dry weight [7]. ASTX (3,3 ′ -dihydroxy-β,β-carotene-4,4 ′ -dione) (Fig. 1), a xantho- phyll carotenoid, consists of two terminal rings linked by a polyene chain with 11 conjugated double bonds, differing from other caroten- oids by the presence of a hydroxyl (-OH) and keto moieties (C=O) on both ends. Due to its particular chemical structure, ASTX exists as ste- reoisomers, geometric isomers, and in the free and esterifed forms. Esterifcation of ASTX may occur due to the presence of hydroxyl (OH) * Corresponding author. Pharmaceutical Technology Laboratory, Department of Pharmaceutical Sciences, Federal University of Santa Catarina, Campus Trindade, Florian´ opolis, SC, 88040-900, Brazil. E-mail address: marta.vieira@inl.int (M.V. Vieira). 1 International Iberian Nanotechnology Laboratory, Food Processing Research Group, Av. Mestre Jos´ e Veiga s/n 4715-330 Braga, Portugal (Present address). Contents lists available at ScienceDirect Journal of Drug Delivery Science and Technology journal homepage: www.elsevier.com/locate/jddst https://doi.org/10.1016/j.jddst.2020.102099 Received 21 May 2020; Received in revised form 9 September 2020; Accepted 10 September 2020