Historical perspective Micro- and nano bio-based delivery systems for food applications: In vitro behavior Lívia de Souza Simões a , Daniel A. Madalena a , Ana C. Pinheiro a,b , José A. Teixeira a , António A. Vicente a , Óscar L. Ramos a,c, ⁎ a CEB - Centre of Biological Engineering, University of Minho, Braga, Portugal b Instituto de Biologia Experimental e Tecnológica, Avenida da República, Quinta-do-Marquês, Estação Agronómica Nacional, Apartado 12, 2781-901 Oeiras, Portugal c LEPABE - Laboratório de Engenharia de Processos, Ambiente, Biotecnologia e Energia, University of Porto, Porto, Portugal abstract article info Available online 27 March 2017 Micro- and nanoencapsulation is an emerging technology in the food field that potentially allows the improve- ment of food quality and human health. Bio-based delivery systems of bioactive compounds have a wide variety of morphologies that influence their stability and functional performance. The incorporation of bioactive com- pounds in food products using micro- and nano-delivery systems may offer extra health benefits, beyond basic nutrition, once their encapsulation may provide protection against undesired environmental conditions (e.g., heat, light and oxygen) along the food chain (including processing and storage), thus improving their bioavail- ability, while enabling their controlled release and target delivery. This review provides an overview of the bio-based materials currently used for encapsulation of bioactive compounds intended for food applications, as well as the main production techniques employed in the development of micro- and nanosystems. The behav- ior of such systems and of bioactive compounds entrapped into, throughout in vitro gastrointestinal systems, is also tracked in a critical manner. Comparisons between various in vitro digestion systems (including the main advantages and disadvantages) currently in use, as well as correlations between the behavior of micro- and nanosystems studied through in vitro and in vivo systems were highlighted and discussed here for the first time. Finally, examples of bioactive micro- and nanosystems added to food simulants or to real food matrices are provided, together with a revision of the main challenges for their safe commercialization, the regulatory is- sues involved and the main legislation aspects. © 2017 Elsevier B.V. All rights reserved. Keywords: Encapsulation Micro/Nanosystems Biomaterials Bioactive compounds Bioavailability Food products Contents 1. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 24 2. Bio-based materials as ingredients for the encapsulating matrix . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 25 2.1. Polysaccharides . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 25 2.2. Proteins . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 25 2.3. Lipids . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 26 2.4. Different combinations of bio-based materials . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 26 3. Bioactive compounds . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 26 3.1. Antioxidants . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 27 3.2. Antimicrobials . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 27 3.3. Vitamins . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 27 3.4. Probiotics and prebiotics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 28 3.5. Other bioactive compounds . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 28 4. Encapsulation techniques . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 29 4.1. Spray drying . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 29 4.2. Freeze drying . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 29 Advances in Colloid and Interface Science 243 (2017) 23–45 ⁎ Corresponding author at: CEB - Centre of Biological Engineering, University of Minho, Braga, Portugal. E-mail address: os.silva.ramos@gmail.com (Ó.L. Ramos). 0001-8686/© 2017 Elsevier B.V. All rights reserved. Contents lists available at ScienceDirect Advances in Colloid and Interface Science journal homepage: www.elsevier.com/locate/cis