Nanomaterials for food applications 9780128141311, 012814131X, 9780128141304

Nanomaterials for Food Applications highlights recent developments in nanotechnologies, covering the different food area

997 162 7MB

English Pages [446] Year 2019

Report DMCA / Copyright

DOWNLOAD FILE

Polecaj historie

Nanomaterials for food applications
 9780128141311, 012814131X, 9780128141304

Table of contents :
Content: 1. Introductory chapter describing the content and organization of the book Part 1. Nanoingredients 2. Nanoformulation for increased bioavailability of food ingredients 3. Nanoencapsulation: techniques and latest developments in the food area 4. Nanoparticles for improved food safety Part 2. Nanotechnologies for food processing 5. Recent developments in nanofiltration 6. Nanocatalysts Part 3: Nanosensors for food quality and safety 7. Nanoparticle-based aptasensors for food contaminant detection 8. Use of nanoparticles as biosensors for food quality assessment Part 4: Nanotechnologies for food packaging and biopackaging 9. Improving polymer and biopolymer performance through the use of nanofillers 10. Nanotechnologies for active and intelligent packaging 11. Bioactive packaging: combining nanotechnologies with packaging for improved food functionality Part 4: Nanotoxicology 12. Methods for nanotechnology risk analysis 13. Current regulatory status of nanotechnologies in food

Citation preview

NANOMATERIALS FOR FOOD APPLICATIONS

This page intentionally left blank

NANOMATERIALS FOR FOOD APPLICATIONS Edited by

 AMPARO LOPEZ RUBIO Preservation and Food Safety Technologies Department, Institute of Agrochemistry and Food Technology (IATA-CSIC), Valencia, Spain

 FABRA ROVIRA MARIA JOSE Preservation and Food Safety Technologies Department, Institute of Agrochemistry and Food Technology (IATA-CSIC), Valencia, Spain

MARTA MARTINEZ SANZ Preservation and Food Safety Technologies Department, Institute of Agrochemistry and Food Technology (IATA-CSIC), Valencia, Spain

  LAURA GOMEZ GOMEZ-MASCARAQUE Food Chemistry and Technology Department, Teagasc Food Research Centre, Moorepark, Ireland

Elsevier Radarweg 29, PO Box 211, 1000 AE Amsterdam, Netherlands The Boulevard, Langford Lane, Kidlington, Oxford OX5 1GB, United Kingdom 50 Hampshire Street, 5th Floor, Cambridge, MA 02139, United States Copyright © 2019 Elsevier Inc. All rights reserved. No part of this publication may be reproduced or transmitted in any form or by any means, electronic or mechanical, including photocopying, recording, or any information storage and retrieval system, without permission in writing from the publisher. Details on how to seek permission, further information about the Publisher’s permissions policies and our arrangements with organizations such as the Copyright Clearance Center and the Copyright Licensing Agency, can be found at our website: www. elsevier.com/permissions. This book and the individual contributions contained in it are protected under copyright by the Publisher (other than as may be noted herein).

Notices Knowledge and best practice in this field are constantly changing. As new research and experience broaden our understanding, changes in research methods, professional practices, or medical treatment may become necessary. Practitioners and researchers must always rely on their own experience and knowledge in evaluating and using any information, methods, compounds, or experiments described herein. In using such information or methods they should be mindful of their own safety and the safety of others, including parties for whom they have a professional responsibility. To the fullest extent of the law, neither the Publisher nor the authors, contributors, or editors, assume any liability for any injury and/or damage to persons or property as a matter of products liability, negligence or otherwise, or from any use or operation of any methods, products, instructions, or ideas contained in the material herein. Library of Congress Cataloging-in-Publication Data A catalog record for this book is available from the Library of Congress British Library Cataloguing-in-Publication Data A catalogue record for this book is available from the British Library ISBN: 978-0-12-814130-4 For information on all Elsevier publications visit our website at https://www.elsevier.com/books-and-journals

Publisher: Matthew Deans Acquisition Editor: Simon Holt Editorial Project Manager: Joshua Mearns Production Project Manager: Swapna Srinivasan Cover Designer: Greg Harris Typeset by TNQ Technologies

To my beloved uncle Vicente Rubio and to all the researchers, like him, who show a true passion for advancing scientific knowledge.

This page intentionally left blank

CONTENTS

Contributors Preface

1. Nanomaterials for Food Applications: General Introduction and Overview of the Book

xiii xvii

1

pez Rubio, Laura G. Go mez-Mascaraque, M.J. Fabra, M. Martínez Sanz Amparo Lo 1.1 1.2 1.3 1.4 1.5

Introduction Potential of Nanotechnologies to Improve Consumer Health Nanotechnologies for Food Processing and Sensing Applications Food Packaging Nanotechnologies Characterization, Toxicological Assessment, and Regulatory Status of Nanomaterials in Food References

1 3 4 6 7 8

Part 1: Nanoingredients 2. Nanostructured Systems to Increase Bioavailability of Food Ingredients

13

María Artiga-Artigas, Isabel Odriozola-Serrano, Gemma Oms-Oliu, Olga Martín-Belloso 2.1 Introduction 2.2 Nanostructured Delivery Systems to Encapsulate Bioactive Compounds 2.3 Bioaccessibility and Bioavailability From Nanoencapsulation Systems 2.4 Industrial Applications 2.5 Future Trends and Concluding Remarks References Further Reading

3. Nanoencapsulation: Techniques and Developments for Food Applications

13 14 19 24 27 28 33

35

Elham Assadpour, Seid Mahdi Jafari 3.1 Introduction 3.2 Nanoencapsulation Versus Microencapsulation 3.3 Classification of Nanoencapsulation Techniques 3.4 Gastrointestinal Fate and Bioavailability of Nanoencapsulated Food Components 3.5 Conclusion and Final Remarks References

35 36 37 53 53 55

vii

viii

Contents

4. Nanostructured Minerals and Vitamins for Food Fortification and Food Supplementation

63

Jesper T.N. Knijnenburg, Lidija Posavec, Alexandra Teleki 4.1 Introduction 4.2 Synthesis Methods of Nanoparticles for Food Applications 4.3 In Vitro and In Vivo Assessment 4.4 Latest Developments in Research 4.5 Critical Evaluation of Nanostructured Food Fortificants and Supplements 4.6 Conclusions and Future Trends References

64 65 68 76 83 84 85

Part 2: Nanotechnologies for Food Processing 5. Recent Developments in Nanofiltration for Food Applications

101

A.W. Mohammad, Y.H. Teow, K.C. Ho, N.A. Rosnan 5.1 Introduction 5.2 Theory and Mechanism of Nanofiltration Membranes 5.3 Applications in Food Industry 5.4 Issues and Challenges List of Abbreviations References

101 102 105 115 116 117

Part 3: Nanosensors for Food Quality and Safety 6. Nanoparticle-Based Aptasensors for Food Contaminant Detection

123

Richa Sharma, K.S.M.S. Raghavarao 6.1 Introduction 6.2 Transduction Approaches for Nanoparticle-Based Aptasensing 6.3 Conclusions and Future Perspective Abbreviations Acknowledgments References Further Reading

123 128 138 139 140 140 144

Contents

7. Nanoparticles as Biosensors for Food Quality and Safety Assessment

147

K.V. Ragavan, Suresh Neethirajan 7.1 Introduction 7.2 Components of Biosensor and Their Properties 7.3 Nanoparticles-Based BiosensorsdClassification 7.4 Semiconductor Quantum Dots 7.5 Perspectives and Conclusions Acknowledgments References

148 149 154 184 193 194 195

Part 4: Nanotechnologies for Food Packaging and Biopackaging 8. Nanotechnology in Food Packaging

205

~oz, Josep Pasqual Cerisuelo, Irene Domínguez, Pilar Hernandez-Mun pez-Carballo, Ramo n Catala, Rafael Gavara Gracia Lo 8.1 8.2 8.3 8.4

Introduction Nanomaterials Used in the Development of Polymer Nanocomposites Applications of Nanocomposites in Food Packaging Human Health Risks and Environmental Impact of Nanotechnology Applied to Food Packaging 8.5 Regulations of Nanotechnology in the Food Sector 8.6 Concluding Remarks References Further Reading

9. Bioactive Packaging: Combining Nanotechnologies With Packaging for Improved Food Functionality

205 206 211 223 226 227 227 232

233

Pablo R. Salgado, Luciana Di Giorgio, Yanina S. Musso, Adriana N. Mauri 9.1 9.2 9.3 9.4

Requirements for Food Packaging: From Traditional Packaging to Bioactive Ones Bioactive Compounds for the Formulation of Bioactive Packaging Development of Nano-Sized Carrier Systems for Bioactive Compounds Effect of Nanostructures on Their Passage Through the Gastrointestinal Tract and Bioavailability

233 236 243 255

ix

x

Contents

9.5 Bioactive Packaging Containing Nanostructures 9.6 Conclusions and Future Trends Acknowledgments References

256 259 260 260

Part 5: Nanotoxicology and Regulatory Status 10. Analytical Challenges and Practical Solutions for Enforcing Labeling of Nanoingredients in Food Products in the European Union

273

Manuel Correia, Eveline Verleysen, Katrin Loeschner 10.1 10.2 10.3 10.4 10.5 10.6

Introduction Potential Sources of Nanoparticles in Food The Issue of Sample Preparation Analytical Methods for Inorganic Nanoparticles in FooddPros and Cons Suggestion for a Screening Strategy for Inorganic Nanoparticles in Food The Next ChallengedAnalysis of Organic and Pure Carbon-Based Particulate Nanomaterials in Food 10.7 Validation Studies and Reference Materials for Nanoparticles in Food 10.8 Conclusions Acknowledgments References

11. Characterization of Nanomaterials: Tools and Challenges

273 275 282 287 295 296 299 302 303 303

313

Thilak Mudalige, Haiou Qu, Desiree Van Haute, Siyam M. Ansar, Angel Paredes, Taylor Ingle 11.1 Introduction 11.2 Challenges of Nanoparticle Analysis in Food Matrices 11.3 Size and Shape Analysis 11.4 Size Separation Techniques 11.5 Crystal Structure 11.6 Elemental Composition Analysis 11.7 Characterization of Surface Chemistry of Nanomaterials 11.8 Summary Abbreviations Acknowledgments References

314 315 318 328 337 337 340 343 344 344 345

Contents

12. Toxicological Hazard Analysis of Nanomaterials With Potential for Utilization in Consumer Goods

355

Ali Kermanizadeh, David M. Brown, Peter Møller 12.1 Introduction 12.2 Physicochemical Characteristics of Nanomaterials Which Govern Potential Toxicity 12.3 Exposure Routes of Nanomaterials 12.4 Summary and Conclusions 12.5 Current and Future Challenges Conflict of Interest Statement References Further Reading

13. Regulatory Status of Nanotechnologies in Food in the EU

355 356 359 369 371 373 373 380

381

Kirsten Rasmussen, Hubert Rauscher, Stefania Gottardo, Eddo Hoekstra, Reinhilde Schoonjans, Ruud Peters, Karin Aschberger 13.1 Introduction 13.2 Regulatory Definitions of Nanomaterial in the European Union 13.3 Overview of EU Legislation Relevant to Food and Nanomaterials 13.4 EU Agencies and Laboratories and the Evaluation Process 13.5 EFSA’s Preparation for Safety Assesment of Nanomaterials 13.6 Conclusions 13.7 Disclaimer Acknowledgments References Index

381 395 396 401 404 405 406 406 407 411

xi

This page intentionally left blank

CONTRIBUTORS Siyam M. Ansar Office of Regulatory Affairs, Arkansas Laboratory, U.S. Food and Drug Administration, Jefferson, AR, United States María Artiga-Artigas Department of Food Technology, University of Lleida e Agrotecnio Center, Lleida, Spain Karin Aschberger European Commission’s Joint Research Centre, Ispra, Italy Elham Assadpour Department of Food Science and Technology, Baharan Institute of Higher Education, Gorgan, Iran David M. Brown Heriot Watt University, School of Engineering and Physical Sciences, Nano Safety Research Group, Edinburgh, United Kingdom Ram on Catala Institute of Agrochemistry and Food Technology, IATA-CSIC, Paterna, Spain Josep Pasqual Cerisuelo Institute of Agrochemistry and Food Technology, IATA-CSIC, Paterna, Spain Manuel Correia Technical University of Denmark, National Food Institute, Division of Food Technology, Lyngby, Denmark Luciana Di Giorgio Centro de Investigaci on y Desarrollo en Criotecnología de Alimentos (CIDCA e CCT La Plata e CONICET) e Facultad de Ciencias Exactas, Universidad Nacional de La Plata (UNLP), Buenos Aires, Argentina Irene Domínguez Institute of Agrochemistry and Food Technology, IATA-CSIC, Paterna, Spain M.J. Fabra Preservation and Food Safety Technologies Department, Institute of Agrochemistry and Food Technology (IATA-CSIC), Valencia, Spain Rafael Gavara Institute of Agrochemistry and Food Technology, IATA-CSIC, Paterna, Spain Laura G. G omez-Mascaraque Food Chemistry and Technology Department, Teagasc Food Research Centre, Moorepark, Ireland Stefania Gottardo European Commission’s Joint Research Centre, Ispra, Italy

xiii

xiv

Contributors

Pilar Hernández-Muñoz Institute of Agrochemistry and Food Technology, IATA-CSIC, Paterna, Spain K.C. Ho Department of Chemical and Process Engineering, Faculty of Engineering and Built Environment, Universiti Kebangsaan Malaysia, Bangi, Malaysia Eddo Hoekstra European Commission’s Joint Research Centre, Ispra, Italy Taylor Ingle National Center for Toxicological Research, U.S. Food and Drug Administration, Jefferson, AR, United States Seid Mahdi Jafari Department of Food Materials and Process Design Engineering, Gorgan University of Agricultural Sciences and Natural Resources, Gorgan, Iran Ali Kermanizadeh Heriot Watt University, School of Engineering and Physical Sciences, Nano Safety Research Group, Edinburgh, United Kingdom; University of Copenhagen, Department of Public Health, Section of Environmental Health, Copenhagen, Denmark Jesper T.N. Knijnenburg International College, Khon Kaen University, Khon Kaen, Thailand Katrin Loeschner Technical University of Denmark, National Food Institute, Division of Food Technology, Lyngby, Denmark Amparo L opez Rubio Preservation and Food Safety Technologies Department, Institute of Agrochemistry and Food Technology (IATA-CSIC), Valencia, Spain Gracia López-Carballo Institute of Agrochemistry and Food Technology, IATA-CSIC, Paterna, Spain Olga Martín-Belloso Department of Food Technology, University of Lleida e Agrotecnio Center, Lleida, Spain M. Martínez Sanz Preservation and Food Safety Technologies Department, Institute of Agrochemistry and Food Technology (IATA-CSIC), Valencia, Spain Adriana N. Mauri Centro de Investigaci on y Desarrollo en Criotecnología de Alimentos (CIDCA e CCT La Plata e CONICET) e Facultad de Ciencias Exactas, Universidad Nacional de La Plata (UNLP), Buenos Aires, Argentina A.W. Mohammad Department of Chemical and Process Engineering, Faculty of Engineering and Built Environment, Universiti Kebangsaan Malaysia, Bangi, Malaysia; Research Center for Sustainable Process Technology (CESPRO), Faculty of Engineering and Built Environment, Universiti Kebangsaan Malaysia, Bangi, Malaysia

Contributors

Peter Møller University of Copenhagen, Department of Public Health, Section of Environmental Health, Copenhagen, Denmark Thilak Mudalige Office of Regulatory Affairs, Arkansas Laboratory, U.S. Food and Drug Administration, Jefferson, AR, United States Yanina S. Musso Centro de Investigaci on y Desarrollo en Criotecnología de Alimentos (CIDCA e CCT La Plata e CONICET) e Facultad de Ciencias Exactas, Universidad Nacional de La Plata (UNLP), Buenos Aires, Argentina Suresh Neethirajan BioNano Laboratory, School of Engineering, University of Guelph, Guelph, ON, Canada Isabel Odriozola-Serrano Department of Food Technology, University of Lleida e Agrotecnio Center, Lleida, Spain Gemma Oms-Oliu Department of Food Technology, University of Lleida e Agrotecnio Center, Lleida, Spain Angel Paredes National Center for Toxicological Research, U.S. Food and Drug Administration, Jefferson, AR, United States Ruud Peters RIKILT, Wageningen UR, Wageningen, The Netherlands Lidija Posavec Previously: Department of Health Sciences and Technology, Swiss Federal Institute of Technology Zurich, Zurich, Switzerland Haiou Qu Office of Regulatory Affairs, Arkansas Laboratory, U.S. Food and Drug Administration, Jefferson, AR, United States K.V. Ragavan BioNano Laboratory, School of Engineering, University of Guelph, Guelph, ON, Canada K.S.M.S. Raghavarao Academy of Scientific and Innovative Research, CSIR-CFTRI, Mysore, India; Department of Food Engineering, CSIR-Central Food Technological Research Institute (CFTRI), Mysore, India Kirsten Rasmussen European Commission’s Joint Research Centre, Ispra, Italy Hubert Rauscher European Commission’s Joint Research Centre, Ispra, Italy N.A. Rosnan Department of Chemical and Process Engineering, Faculty of Engineering and Built Environment, Universiti Kebangsaan Malaysia, Bangi, Malaysia

xv

xvi

Contributors

Pablo R. Salgado Centro de Investigaci on y Desarrollo en Criotecnología de Alimentos (CIDCA e CCT La Plata e CONICET) e Facultad de Ciencias Exactas, Universidad Nacional de La Plata (UNLP), Buenos Aires, Argentina Reinhilde Schoonjans European Food Safety Authority, Parma, Italy Richa Sharma Academy of Scientific and Innovative Research, CSIR-CFTRI, Mysore, India; Department of Food Engineering, CSIR-Central Food Technological Research Institute (CFTRI), Mysore, India; Department of Biotechnology, Sharda University, Greater Noida, India Alexandra Teleki Department of Pharmacy, Uppsala University, Uppsala, Sweden Y.H. Teow Department of Chemical and Process Engineering, Faculty of Engineering and Built Environment, Universiti Kebangsaan Malaysia, Bangi, Malaysia; Research Center for Sustainable Process Technology (CESPRO), Faculty of Engineering and Built Environment, Universiti Kebangsaan Malaysia, Bangi, Malaysia Desiree Van Haute Office of Regulatory Affairs, Arkansas Laboratory, U.S. Food and Drug Administration, Jefferson, AR, United States Eveline Verleysen Service Trace Elements and Nanomaterials, Sciensano, Brussels, Belgium

PREFACE

The last decades have witnessed an increased interest in the use of nanomaterials in a number of different scientific and industrial areas, including the food industry. In fact, the use of nanomaterials for food applications is a rapidly evolving field and, given the specific properties of nanomaterials and their tremendous potential, an increased number of material innovations which contribute to improved food quality and safety are foreseen. In this book, we have tried to compile the latest developments reviewed by renowned experts related to the various uses of nanomaterials in the food area, to set the basis for future inspiration. Although the possibilities are unlimited, nanomaterials in the food area could be divided in several broad groups, corresponding to different sections within this publication. The first group consists of nanomaterials for improved food quality. In this sense, the use of nanoingredients to enhance nutrient absorption or nanotechnology tools (like nanoemulsions or nanoencapsulation) for functional food development has proved successful. The challenges in this area rely on a more thorough knowledge for the proper selection of materials to attain the desired properties in terms of protection, release, and digestion. In vivo behavior of these nanoingredients within complex food matrices is another area which deserves investigation, as a few works have demonstrated that the properties of the nanomaterials can be modified as a consequence of their interaction with other food components. The second big group relates to nanomaterials for improved food safety. Nanosensors and nanocomposites for food packaging applications are some of the nanomaterials which can be included in this group. Regarding the nanosensors, the ability of nanoparticles to be functionalized, together with their recognition and transducing properties, and the possibility to combine them with biosensors opens up a great number of possibilities to develop highly sensitive tools that guarantee food safety (there are a couple of chapters devoted to these interesting issues). In the food packaging area, specifically for polymeric and biopolymeric materials, incorporation of well-dispersed nanoparticles (organic and inorganic) has demonstrated their ability to improve mechanical, thermal, and barrier properties without affecting the optical characteristics of the materials. This is probably the area within the food nanotechnology field where more research has been done giving rise to various commercial products. From several years ago, there have been research efforts put on going a step further and, thus, the use of these nanoparticles are aimed, not only at improving the quality and safety of the packaged food passively, but at playing an active role in food preservation and food quality enhancement. These novel materials are known as active/bioactive packages, which are able to release/absorb certain substances to change either the inner packaging atmosphere or even the food product. The aim of

xvii

xviii

Preface

combining these active/bioactive substances included in the packaging structure with nanoparticles is to modulate their release or sorption or even to use the nanoparticles as active substances themselves (such as antimicrobial packages containing nanometals). However, it is also true that very little is known about the potential migration of nanoparticles from the packages and their subsequent potential toxicity, and there is also controversy regarding the use of nanoingredients and the need of “nanolabelling” the food products. Therefore, a complete section written by toxicology experts with clues about the toxicological assessment of food-related materials containing nanoparticles and legislation authorities (both from Europe and the United States) has been included in the book. We sincerely hope that you enjoy the book as much as we have enjoyed editing it. The Editors Valencia

CHAPTER 1

Nanomaterials for Food Applications: General Introduction and Overview of the Book  pez Rubio1, Laura G. Go  mez-Mascaraque2, M.J. Fabra1, Amparo Lo 1 M. Martínez Sanz

1 Preservation and Food Safety Technologies Department, Institute of Agrochemistry and Food Technology (IATA-CSIC), Valencia, Spain; 2Food Chemistry and Technology Department, Teagasc Food Research Centre, Moorepark, Ireland

Contents 1.1 Introduction 1.2 Potential of Nanotechnologies to Improve Consumer Health 1.3 Nanotechnologies for Food Processing and Sensing Applications 1.4 Food Packaging Nanotechnologies 1.5 Characterization, Toxicological Assessment, and Regulatory Status of Nanomaterials in Food References

1 3 4 6 7 8

1.1 INTRODUCTION Nanotechnology refers to the manufacturing, characterization, and manipulation of materials with at least one of the dimensions in the nanometer scale (below 0.1 mm). Although the description of nanotechnology is purely in terms of the size, it is important to emphasize that, at this scale, rearranging the atoms and molecules leads to changes in physicochemical properties in comparison to the same material at larger size scales. Specifically, the decrease in size has associated much larger specific surface area with a subsequent enhanced surface reactivity and, for instance, increased ion release (Peters et al., 2016). Applications of nanotechnologies in the food sector are rapidly growing, with an amazing boost on the number of the publications, patents and intellectual property rights in the field, and interesting nanotechnology-related developments in food processing, packaging, nutraceutical delivery, quality control, and functional foods among others (Dasgupta et al., 2015). In fact, nanotechnology is considered to be one of the six key enabling technologies for Europe (European Commission, 2016), given its potential for the development of innovative products and applications in several industrial sectors including food production, food processing, novel foods, food additives, and food contact materials (Chaudhry et al., 2008; Kah et al., 2013; Kah and Hofmann, 2014; Sekhon, 2010, 2014).

Nanomaterials for Food Applications ISBN 978-0-12-814130-4, https://doi.org/10.1016/B978-0-12-814130-4.00001-4

© 2019 Elsevier Inc. All rights reserved.

1

2

Nanomaterials for Food Applications

Investment in nanotechnology has burst in the past years. In fact, nearly every major funding agency has a budget devoted to this research area, and it is expected that by 2020, products incorporating nanotechnologies will contribute approximately $1 trillion to the global economy, being about two million workers employed in nanotech industries, and three times that many having supporting jobs. The two existing approaches to generate nanoparticles or nanodevices are the topdown approach (i.e., breaking up bigger particles) or the bottom-up approach that consists of atom-by-atom engineering. This last strategy can be accomplished either using nanoscale engineering tools (such as electron-beam and ion-beam fabrication or nanoimprint lithography) or through the self-assembly of molecules such as in the case of amphiphilic molecules to form micelles. And regarding the characteristics that make nanomaterials so attractive, the first one is, of course, related with the size, as such small sizes have advantages both from economical point of view and application-wise. However, as mentioned before, at these mesoscales new phenomena occur, which is relevant in areas such as electronics. Moreover, the ability of arranging atom-by-atom provides with an extremely high design control, allowing for huge possibilities in terms of product development. In the food area, nanotechnologies can be applied along the whole cycle of product development, from the production of nanoingredients or nanofertilizers for food production, through the use of nanotechnologies for food processing (for instance, nanofiltration technologies) to even the use of nanosensors or nano-noses to assure food quality and safety. According to several consulting agency reports, in the food area, the overall size of the global nanotechnology market is estimated to be worth more than $20 billion with an upward trend and being led by the United States, followed by Japan and China (Cientifica Report, 2006; Helmut Kaiser Consultancy, 2004; Nanoposts Report, 2008). Most of the food giants including Nestle, Kraft, Heinz, and Unilever support specific research programs to capture a share of the nanofood market in the next decade. The main food-related areas where nanotechnologies have a great potential are food packaging (nanocomposites, active, bioactive, and intelligent packaging), functional foods, and nutraceuticals (through the use of nanoencapsulation or nanoformulations), food processing (using technologies such as nanofiltration), and food safety and quality (through the use of nanosensors, nanotongues, and nano-noses). However, for the successful establishment of nanotechnologies in the food sector, a number of technological, societal, and regulatory barriers need to be overcome. The real benefits of these technologies for consumers and the evaluation of the potential risks associated to consumption of, or exposure to nanoparticles need to be deeply analyzed and communicated to society. Therefore, this book was conceived to provide current knowledge about the benefits that these novel technologies may have in the food sector, as well as their current

Nanomaterials for Food Applications: General Introduction and Overview of the Book

regulatory status and the challenges encountered when trying to characterize and/or quantify the nanomaterials present in complex food matrices.

1.2 POTENTIAL OF NANOTECHNOLOGIES TO IMPROVE CONSUMER HEALTH One of the areas in which nanotechnologies play a relevant role in the food sector is the development of functional foods, which are food products especially designed to provide health benefits beyond their basic nutritional value (Day et al., 2009). The design of these products usually involves the addition of exogenous bioactive ingredients to a conventional food matrix (Kaur and Das, 2011), and this entails a series of challenges. First of all, most bioactive ingredients are sensitive and can lose activity during manufacturing, storage, commercialization, and/or consumption (G omez-Mascaraque et al., 2015). Moreover, some of these compounds are immiscible with the food matrix in which they are to be incorporated, some can alter the organoleptic properties of the final food products, and many of them have poor bioavailabilities (Deng et al., 2014; Lafarga and Hayes, 2017). These limitations can only be overcome through adequate formulation and/or encapsulation strategies to protect, transport, and deliver the ingredients of interest. In this context, nanotechnologies are a promising alternative to conventional techniques because the miniaturization of the delivery vehicles generally results in a reduced impact on the textural properties of the products, an improved product stability, and an enhanced absorption of the bioactive ingredients, due to their greater surface-tovolume ratio (McClements, 2015). There are already several commercial food products in the market containing nanosized delivery vehicles, such as the “Tip-Top” Up bread, commercialized in Australia, which contains fish oil nanocapsules, which are a source of omega-3 fatty acids. The capsules are designed to break open only when they have reached the stomach, thus avoiding the unpleasant/strong taste of fish oil. Another commercial example is from the Israeli Company NutraLease, which uses expanded micelles (hollow spheres made from fats, with an aqueous interior) with a diameter of approximately 30 nm. The nutrients or “nutraceuticals” are contained within the aqueous interior. The technology has already been adopted and marketed by Shemen Industries to deliver Canola Active oil, which it claims reduces cholesterol intake into the body by 14%, by competing for bile solubilization. An example of nanotechnologies used in the nutraceutical sector is the Spray For Life product range manufactured by Health Plus International. They use a newly designed Nanoceutical Delivery System for oral administration of dietary supplements, resulting in increased bioavailability compared with gastrointestinal absorption. Apart from the aforementioned commercial food products, a number of nanosized delivery vehicles and formulations have already been developed and are currently being

3

4

Nanomaterials for Food Applications

investigated for their potential use for food applications. These include nanoemulsions, nanoliposomes, lipid nanoparticles, biopolimeric nanoparticles and coacervates, and nanohydrogels. Chapter 2 of the present book provides an overview of the different nanostructured delivery systems, which can be applied for the formulation of food ingredients, with a special emphasis on the impact that their nanostructure and physicochemical properties have on the bioavailability of the functional ingredients entrapped within them. In general, a reduction in the droplet or particle size increases their bioaccessibility (Yallapu et al., 2011). A review of recent research works evaluating the role of nanoformulation and nanoencapsulation of bioactive food ingredients on their bioaccesibility and bioavailability is also provided in the second chapter, summarizing findings obtained from experiments conducted both in vitro and in vivo. Finally, their industrial applications are also discussed. The classification of the nanoencapsulation techniques used to produce the diverse range of nanostructured delivery vehicles commented above is complex and variable because of the diversity of existing technologies. Nevertheless, Chapter 3 aims at providing a systematic classification and description of these technologies by dividing them into five different groups ( Jafari, 2017). These include nanoencapsulation within biopolymer nanoparticles, lipid-based nanoencapsulation systems, nature-inspired nanocarriers (such as caseins, cyclodextrins, or amylose nanohelices), novel nanoencapsulation systems produced using advanced equipment and technologies (such as electrospinning, electrospraying, nanospray-drying, or micro- and nanofluidics), and other miscellaneous nanoencapsulation systems such as nanocrystals, dendrimers, or niosomes. The application of these technologies for the nanoencapsulation of different bioactive ingredients, including phenolic compounds, antimicrobial agents, bioactive oils, carotenoids, and other food colorants, among others, is also reviewed in the third chapter. Given that minerals and vitamins are essential nutrients for humans and that insufficient intake of these micronutrients affects billions of people worldwide (Bailey et al., 2015), Chapter 4 of this book is especially dedicated to the nanoformulation of these bioactive ingredients for food fortification and supplementation purposes. Again, by decreasing the particle size down to the nanoscale, the bioavailability of minerals and vitamins can be improved, although the impact of nanostructuring these ingredients on their toxicity must be also evaluated because it may result in adverse effects.

1.3 NANOTECHNOLOGIES FOR FOOD PROCESSING AND SENSING APPLICATIONS Nanotechnology has also brought significant advances within the food processing area. Because of the high-quality standards required for food products and the increasing demand on emerging products such as low fat and low calorie products and foodstuffs adapted for special dietary requirements, improved separation methods are needed within

Nanomaterials for Food Applications: General Introduction and Overview of the Book

the food industry. One of the most relevant nanotechnology-based methods with a great potential for food processing applications is nanofiltration. Membranes with nanopores can be used, for instance, for water purification and softening, as such nanofilters are able to remove divalent ions. This nanotechnology is also very useful in the dairy industry for several applications, such as to fractionate milk proteins, for enhancing the microbial quality of dairy fluids (as the membranes also remove bacteria), and for the standardization of milk. Among the several advantages of this technique over conventional filtration processes, it is worth highlighting its lower energy consumption, lesser processing steps, greater separation efficiency, and improved final product quality. Chapter 5 presents the basic principles of the nanofiltration process, followed by an overview of the recent developments of this processing method for several industrial applications such as dairy products, beverages, sugar, wastewater treatment, and vegetable oils, as well as the challenges that need to be addressed to improve nanofiltration for its large-scale application within the food industry. Nanotechnology has also led to significant advances within the food safety area. Currently, there is a high demand on robust, fast, and sensitive detection techniques for food contaminants. In this context, biosensing techniques, which rely on highly specific bioreceptors coupled with efficient transducing systems, are the most efficient approach for the specific recognition of food contaminants, in the presence of highly complex food matrices. These bioreceptors need to be strongly and selectively binding biomolecules for a specific target compound, producing a chemical or biological signal that is converted to a measurable form by the transducer. Aptamers are single-stranded nucleic acid or peptide molecules that have high affinity to only their target ligands, similar to antibodies, but much simpler to synthesize and modify. One commercial example of biosensing for the detection of food contaminants is the Nanobioluminescence Detection Spray from the company Agromicron, which is based on a luminescent protein that emits a visible glow when it reacts with the surface of some pathogenic microorganisms such as Salmonella or Escherichia coli. Chapter 7 presents an overview of the unique physicochemical advantages of nanomaterials as efficient signal transducers and amplifiers, in conjunction with the selectivity and flexibility of aptamers. The different nanomaterial-based aptasensing techniques for food safety are presented and some of the most relevant examples of application are also discussed in this chapter. Food quality and safety are the two most important aspects focused in food processing industry. Analytical procedures and instrumentation are sufficiently equipped to determine food quality and hazards (contaminants and adulterants) at very low concentration with great accuracy in complex food matrices. However, because these instruments and their services are expensive, they required trained/skilled personnel and they are timeconsuming to obtain the results. Hence, there is a need for simple, affordable, field applicable sensor systems with sufficient analytical performance for the evaluation of food

5

6

Nanomaterials for Food Applications

safety and quality. Chapter 8 reviews the interest of biosensors for fulfilling the above requirements and with the advent of nanotechnology. The discovery of nanomaterial properties in recent times and their integration with biosensors have further helped to progress in the field. This chapter presents an overview of various components of biosensors, their properties, and recent advances with respect to food safety and quality. At the end, perspective and scope of nanomaterial properties along with challenges in the field of biosensors for food industry are also discussed.

1.4 FOOD PACKAGING NANOTECHNOLOGIES Within the food-packaging sector, the nanocomposites area is the most active one in terms of food nanoscience research. The use of biodegradable plastics and resources are seen as one of the many strategies to minimize the environmental impact of petroleum-based plastics. However, most of the biobased packaging materials do not perform as the petroleum-based ones and some of their physical properties such as barrier, thermal stability, and mechanical properties need to be improved. The nanoreinforcement of biobased plastics through the incorporation of nanoclays, micro- and nanofibers of cellulose, and carbon nanofibers and nanotubes has been proven to be an effective way to enhance these properties concurrently (Sanchez-García et al., 2010; Trifol et al., 2016; Vilarinho et al., 2017). Some of the advantages of using nanofillers instead of the previously used microfillers is that with very low percentages of loading, typically below 10%, relevant physical improvements can be achieved without compromising desirable matrix properties such as transparency or toughness (Mondragon et al., 2015; Vilarinho et al., 2017). Moreover, the greatest specific surface of the nanofillers improves the adhesion with the matrix and thus better final properties can be obtained. All these aspects, together with the environmental impact of nanotechnology applied to food packaging are discussed in more detail in Chapter 9. Moreover, the application of metallic nanoparticles with antimicrobial or antioxidant properties embedded in polymeric films for the development of active packages is also addressed in this chapter. New technologies of food packaging try to respond to society demands. Thus, bioactive packaging has the unique role of enhancing food impact over consumers’ health through the generation of healthier packaged foods. In this sense, it can be considered as an innovative strategy in the production of functional foods. The use of nanotechnologies also opened new possibilities for improving the effectiveness of these packages, and many nanoparticles have been developed because of their potential to encapsulate active compounds and increase their functionality, stability, and bioavailability. The incorporation of nanoparticles within the packaging structure, together with the active or bioactive substances, would permit a controlled release of these additives, diminishing the impact on materials properties (Imran et al., 2010; L opez-Rubio et al., 2006). Chapter 10 focuses on the application of nanotechnology in the development of bioactive packaging. It

Nanomaterials for Food Applications: General Introduction and Overview of the Book

analyses the requirements of current food packaging, describes the main bioactive compounds for the preparation of bioactive packaging and studies the development of nano-sized carrier systems and different strategies in the preparation of nanostructured packaging materials to improve the stability, dispersibility, availability, and transport of bioactive compounds.

1.5 CHARACTERIZATION, TOXICOLOGICAL ASSESSMENT, AND REGULATORY STATUS OF NANOMATERIALS IN FOOD To understand the challenges for proper characterization and risk assessment of nanotechnologies in food, it is important to emphasize that nanoparticles can be either naturally present in the food products, intentionally added, nonintentionally incorporated (either through migration or environmental contamination), or can even be formed during food processing. A clear example of a naturally containing food is milk, where casein micelles of about 100 nm coexist with whey proteins having a size of about 30 nm. In fact, many food proteins exist naturally in the nanoscale and simple triglyceride lipids are about 2-nm long. We can also find nanoparticles in traditionally processed food products, especially in emulsions such as mayonnaise. Furthermore, during digestion, food is broken down to nanostructures before assimilation and, thus, the food compounds are metabolized in the body at a nanoscale. And although it is still unclear whether nanoscale processing of food materials might produce structures that are different from those that occur naturally, a fair classification before evaluating potential risks should be carried out to clearly distinguish between nanoparticles produced from food-grade materials and inorganic or engineered nanoparticles (such as nanometals or carbon nanotubes and nanofibers). Anyway, considering not only the different potential sources of nanoparticles and the inherent complexity of food matrices, for nanoparticle quantification and characterization, a proper sample preparation has to be carried out and the selection of the analytical tools are key for obtaining reliable results. All these aspects are dealt with in Chapters 10 and 11. Regarding the factors related to toxicity, without any doubt the dose is the main factor to take into account. Other important factors are the entrance route and certain intrinsic factors that depend on the type of nanoparticle, such as the size, shape, composition, charge, and if nanoparticles are coated, aggregation, biodegradability, biodistribution, etc. All these aspects, together with the current knowledge about the health impact that certain nanoparticles may have on ingestion or exposure are discussed in more detail in Chapter 12. There are several international agencies that have elaborated protocols or guides for nanotechnology-related risk evaluation, such as the French OECD or the International Standards Organization. The European Food Safety Authority published a guide for risk analysis in food products, which include the identification and characterization of

7

8

Nanomaterials for Food Applications

nanomaterials and the identification of risks, both in vitro and in vivo. This guide (see Chapter 13) includes a series of tests that should be carried out, some of them necessary and others specific for certain applications. Although the number of research works about nanoparticle toxicological assays has increased considerably in the last years, experts in the area have found that many of them have been carried out by nonexperienced researchers, being incomplete, using excessive nanoparticle doses or leading to wrong conclusions. On the other hand, food industries are still reticent to publically declare if they work or use nanotechnologies (probably due to potential consumer rejection) and, thus, to ensure the proper spreading of these nanotechnologies, a standardization of the methodologies for risk and toxicity assessment to guarantee the safety of any material to be included in food products deems necessary. The details about the current regulatory status of nanotechnologies in the European Union are compiled in Chapter 13.

REFERENCES Bailey, R.L., West, K.P., Black, R.E., 2015. The epidemiology of global micronutrient deficiencies. Annals of Nutrition and Metabolism 66, 22e33. Chaudhry, Q., Scotter, M., Blackburn, J., Ross, B., Boxall, A., Castle, L., et al., 2008. Applications and implications of nanotechnologies for the food sector. Food Additives and Contaminants - Part A Chemistry, Analysis, Control, Exposure and Risk Assessment 25, 241e258. Cientifica Report, 2006. Nanotechnologies in the Food Industry. Dasgupta, N., Ranjan, S., Mundekkad, D., Ramalingam, C., Shanker, R., Kumar, A., 2015. Nanotechnology in agro-food: from field to plate. Food Research International 69, 381e400. Day, L., Seymour, R.B., Pitts, K.F., Konczak, I., Lundin, L., 2009. Incorporation of functional ingredients into foods. Trends in Food Science and Technology 20 (9), 388e395. Deng, X.X., Chen, Z., Huang, Q., Fu, X., Tang, C.H., 2014. Spray-drying microencapsulation of b-carotene by soy protein isolate and/or OSA-modified starch. Journal of Applied Polymer Science 131 (12). European Commission, 2016. http://ec.europa.eu/growth/industry/key-enablingtechnologies/index_en.htm. G omez-Mascaraque, L.G., Lagar on, J.M., L opez-Rubio, A., 2015. Electrosprayed gelatin submicroparticles as edible carriers for the encapsulation of polyphenols of interest in functional foods. Food Hydrocolloids 49 (0), 42e52. Helmut Kaiser Consultancy, 2004. Study: Nanotechnology in Food and Food Processing Industry Worldwide 2003e2006e2010e2015. Available at: www.hkc22.com/Nanofood.html. Imran, M., Revol-Junelles, A.-M., Martyn, A., Tehrany, E.A., Jacquot, M., Linder, M., Desobry, S., 2010. Active food packaging evolution: transformation from micro- to nanotechnology. Critical Reviews in Food Science and Nutrition 50 (9), 799e821. Jafari, S.M., 2017. An overview of nanoencapsulation techniques and their classification. In: Nanoencapsulation Technologies for the Food and Nutraceutical Industries. Academic Press, pp. 1e34. Kah, M., Hofmann, T., 2014. Nanopesticide research: current trends and future priorities. Environment International 63, 224e235. Kah, M., Beulke, S., Tiede, K., Hofmann, T., 2013. Nanopesticides: state of knowledge, environmental fate, and exposure modeling. Critical Reviews in Environmental Science and Technology 43, 1823e1867. Kaur, S., Das, M., 2011. Functional foods: an overview. Food Science and Biotechnology 20 (4), 861e875. Lafarga, T., Hayes, M., 2017. Bioactive protein hydrolysates in the functional food ingredient industry: overcoming current challenges. Food Reviews International 33 (3), 217e246. L opez-Rubio, A., Gavara, R., Lagaron, J.M., 2006. Bioactive packaging: turning foods into healthier foods through biomaterials. Trends in Food Science and Technology 17, 567e575.

Nanomaterials for Food Applications: General Introduction and Overview of the Book

McClements, D.J., 2015. Nanoscale nutrient delivery systems for food applications: improving bioactive dispersibility, stability, and bioavailability. Journal of Food Science 80 (7), N1602eN1611. Mondragon, G., Pe~ na-Rodriguez, C., Gonzalez, A., Eceiza, A., Arbelaiz, A., 2015. Bionanocomposites based on gelatin matrix and nanocellulose. European Polymer Journal 62, 1e9. Nanoposts Report, 2008. Nanotechnology and Consumer Goods e Market and Applications to 2015. Nanoposts.com. Peters, R.J.B., Bouwmeester, H., Gottardo, S., Amenta, V., Arena, M., Brandhoff, P., Marvin, H.J.P., Mech, A., Moniz, F.B., Pesudo, L.Q., Rauscher, H., Schoonjans, R., Undas, A.K., Vettori, M.V., Weigel, S., Aschberger, K., 2016. Nanomaterials for food products and applications in agriculture, feed and food. Trends in Food Science and Technology 54, 155e164. Sanchez-García, M.D., Lopez-Rubio, A., Lagaron, J.M., 2010. Natural micro and nanobiocomposites with enhanced barrier properties and novel functionalities for food biopackaging applications. Trends in Food Science and Technology 21 (11), 528e536. Sekhon, B.S., 2010. Food nanotechnology - an overview. Nanotechnology, Science and Applications 3, 1e15. Sekhon, B.S., 2014. Nanotechnology in agri-food production: an overview. Nanotechnology, Science and Applications 7, 31e53. Trifol, J., Plackett, D., Sillard, C., Hassager, O., Daugaard, A.E., Bras, J., Szabo, P., 2016. A comparison of partially acetylated nanocellulose, nanocrystalline cellulose, and nanoclay as fillers for high-performance polylactide nanocomposites. Journal of Applied Polymer Science 133 (14). Article No: 43257. Vilarinho, F., Sanches Silva, A., Vaz, M.F., Farinha, J.P., 2017. Nanocellulose in green food packaging. Critical Reviews in Food Science and Nutrition 1e12. Yallapu, M.M., Jaggi, M., Chauhan, S.C., 2011. Design and engineering of nanogels for cancer treatment. Drug Discovery Today 16 (9e10), 457e463.

9

This page intentionally left blank

PART 1

Nanoingredients

This page intentionally left blank

CHAPTER 2

Nanostructured Systems to Increase Bioavailability of Food Ingredients María Artiga-Artigas, Isabel Odriozola-Serrano, Gemma Oms-Oliu, Olga Martín-Belloso Department of Food Technology, University of Lleida e Agrotecnio Center, Lleida, Spain

Contents 2.1 Introduction 2.2 Nanostructured Delivery Systems to Encapsulate Bioactive Compounds 2.2.1 Nanoemulsions 2.2.2 Nanoliposomes 2.2.3 Nanohydrogels 2.2.4 Lipid Nanoparticles 2.2.4.1 Solid-Lipid Nanoparticles 2.2.4.2 Nanostructured Lipid Carriers

2.2.5 Coacervates 2.3 Bioaccessibility and Bioavailability From Nanoencapsulation Systems 2.3.1 In vitro Experiments 2.3.2 In vivo Experiments 2.4 Industrial Applications 2.5 Future Trends and Concluding Remarks References Further Reading

13 14 14 16 17 18 18 18

19 19 19 22 24 27 28 33

2.1 INTRODUCTION Nanotechnological processes allow the production of particles that are one-billionth of a meter in diameter (nanometer), leading to structures that may have unique and novel functional properties in comparison with the same materials at conventional sizes. This is possible because these techniques are able to increase the surface area by reducing the size of matter, and this causes a greater interaction with other particles as a result (Weiss et al., 2006). In the last decade, nanotechnology has been widely used by industries including cosmetics, pharmaceuticals, agriculture, and food. Specifically, the increasing consumer’s demand for healthy and safe foods is stimulating innovation and new product development in the food industry, which is also the cause of the expanding worldwide interest in functional foods (Lopez-Rubio et al., 2006). Functional ingredients such as vitamins, antimicrobials, natural colorants, and flavorings, among others, Nanomaterials for Food Applications ISBN 978-0-12-814130-4, https://doi.org/10.1016/B978-0-12-814130-4.00002-6

© 2019 Elsevier Inc. All rights reserved.

13

14

Nanomaterials for Food Applications

have been commonly added to industrial food products. Nonetheless, the incorporation of these compounds may cause organoleptic changes in the original product such as odor, flavor, or color alterations (Bourbon et al., 2016a). Moreover, active ingredients are presented in a number of different molecular and physical forms such as polarities (polar, nonpolar, amphiphilic), molecular weights (low to high), and physical states (solid, liquid, gas), being usually sensitive to external factors such as light, temperature, or pH, which could cause its degradation and loss of functionality. To preserve the activity of these substances, protecting them against biological or physicochemical degradation, functional ingredients can be incorporated into some form of delivery system (Weiss et al., 2006). These systems can protect the bioactive compounds until they can be used by the body and without losing their activity, working as chemical and/or physical barriers. Eventually, these systems could be able to control the release of functional ingredients under specific conditions such as pH, UV-light, ionic strength, or temperature to optimize their action (Fathi et al., 2012). Furthermore, it is reported that if these delivery systems are nanostructured, the bioavailability of the compounds encapsulated within them after passage through the gastrointestinal (GI) tract and the response to environmental changes may increase due to their small size (Oh et al., 2009; Patel and Sawant, 2007; Yallapu et al., 2011). That is possible because of the mentioned higher surface area of nanoparticles in comparison with bigger ones, which results in greater interactions with other particles (Bourbon et al., 2016a; Weiss et al., 2006).

2.2 NANOSTRUCTURED DELIVERY SYSTEMS TO ENCAPSULATE BIOACTIVE COMPOUNDS Technological advances such as developments in electronic microscopy and other imaging techniques allow studying food structure and also developing and characterizing nanosized systems aimed at encapsulating, transporting, and releasing bioactive ingredients. Actually, this fact has captured the interest of scientist during the last decades. The feasibility of studying these structures in detail allows understanding their properties and facilitates their manipulation to obtain novel and high quality and safety foods (Livney, 2015). Concerning the advantages of using delivery systems as carriers of bioactive ingredients, the progress in the preparation and study of these systems is continuously growing. Currently, some of the most studied nanostructured delivery systems are nanoemulsions, nanoliposomes, nanohydrogels, lipid nanoparticles, and coacervates, whose structures have been schematized in Fig. 2.1.

2.2.1 Nanoemulsions In general, a nanoemulsion consists of at least two immiscible phasesdnormally water and oildwith one of them dispersed as small spherical droplets (75%) and stability after ingestion (85%), and good capacity for increasing the oral bioavailability and bioaccessibility of poorly bioaccessible ingredients such as curcuminoids or isoflavones (Aditya et al., 2013). Moreover, regarding their capacity to permeate through the membranes and target effectively specific tissues after parenteral administration, it is considered that SLNs combine the advantages of polymeric nanoparticles, fat emulsions, and liposomes. In addition, they can be produced at industrial scale using high-pressure homogenization (Luo et al., 2006; Rodríguez et al., 2016).

Nanostructured Systems to Increase Bioavailability of Food Ingredients

To take advantage of their capacities, Gobbi et al. (2010) suggested a new application of lipid nanoparticles for imaging probes, which expands their field of development (Wen et al., 2017). Finally, biopolymer complexes and coacervates, normally based on proteins and polysaccharides, have emerged as a potential tool to produce specific microstructures and novel functionalities with potential application in the food, pharmaceutical, or cosmetic industries. However, concerning their incorporation within food products, these complexes should present desirable rheological, interfacial, and textural properties to enhance the quality and nutritional aspects of foods, as well as the bioavailability or absorption of active entrapped ingredients(Martins et al., 2013; Salminen and Weiss, 2014; Schmitt and Turgeon, 2011; Turgeon et al., 2003). Overall, to ensure the safety of these systems for human beings and minimize the risks, it is necessary to take into account the most relevant aspects of the nanoparticles, such as the behavior of the constituents of the ingested nanosized systems, before their preparation can be exploited by the food industry. Additionally, an exhaustive evaluation of the dose range, organ distribution, and clearance of nanoparticles, together with the availability and degradation of nanoparticle constituents and toxicity associated with the released products, is needed. This is because the constituents of nanoparticles may experiment degradation after being administered in animals and hence, the determination of availability and pharmacokinetic properties of nanoparticles is essential. In addition, immunotoxicity mediated by nanoparticles has to be tested because nanoparticles can produce immune responses. Therefore, it is of outmost importance to determine whether the nanoparticles or their constituent parts trigger any immune reactions (Sharma et al., 2012).

2.5 FUTURE TRENDS AND CONCLUDING REMARKS The incorporation of nanostructured systems to foods may be a great strategy to enhance the bioavailability and bioaccessibility of encapsulated functional compounds with economic feasibility, at least at laboratory scale. It is for that reason that there is an evident interest in the use of nanostructured systems for the encapsulation, protection, transport, specific targeting, and release of functional compounds because they present potential advantages in comparison with conventional structures in several sectors of industry. Their ability to modulate the biological fate of bioactive ingredients within human body and to control their release under certain conditions seems to be a promising advantage for the design of functional nanoparticles. Several research works have concluded that, in general, lipid nanoparticles produce more interesting results for the medical field, whereas nanoemulsions and coacervates or nanohydrogels develop a widely range of applications for the food or pharmacological industry, respectively. Nonetheless, the extrapolation of nanostructured systems to the industrial scale is still

27

28

Nanomaterials for Food Applications

a challenge. The principal limitation resides in the understanding of the toxicological effects that nanoparticles could cause or not in the human body after ingestion. In this regard, despite the fact that it is demonstrated that nanoparticles are able to enhance food quality, safety, and bioaccessibility of the encapsulated compounds, a global interest and debate has to exist among the scientific community regarding the associated side effects that nanoparticles might cause on living organisms. This would allow determining the real and general impact on consumers. To achieve this purpose, the characterization of nanostructured systems should be the first essential part of assessing nanotoxicology. For this reason, although the field of design and production of nanostructured delivery systems is progressing quickly, an extensive development of not hazardous materials for human’s health is required.

REFERENCES Acevedo-Fani, A., Salvia-Trujillo, L., Rojas-Gra€ u, M.A., Martín-Belloso, O., 2015. Edible films from essential-oil-loaded nanoemulsions: physicochemical characterization and antimicrobial properties. Food Hydrocolloids 47, 168e177. Aditya, N.P., Shim, M., Lee, I., Lee, Y., Im, M.-H., Ko, S., 2013. Curcumin and genistein coloaded nanostructured lipid carriers: in vitro digestion and antiprostate cancer activity. Journal of Agricultural and Food Chemistry 61 (8). Ahmed, E.M., 2015. Hydrogel: preparation, characterization, and applications: a review. Journal of Advanced Research 6 (2), 105e121. Ahmed, K., Li, Y., McClements, D.J., Xiao, H., 2012. Nanoemulsion- and emulsion-based delivery systems for curcumin: encapsulation and release properties. Food Chemistry 132 (2), 799e807. Anand, P., Nair, H.B., Sung, B., Kunnumakkara, A.B., Yadav, V.R., Tekmal, R.R., Aggarwal, B.B., 2010. Design of curcumin-loaded PLGA nanoparticles formulation with enhanced cellular uptake, and increased bioactivity in vitro and superior bioavailability in vivo. Biochemical Pharmacology 79 (3), 330e338. Artiga-Artigas, M., Acevedo-Fani, A., Martín-Belloso, O., 2017. Improving the shelf life of low-fat cut cheese using nanoemulsion-based edible coatings containing oregano essential oil and mandarin fiber. Food Control 76, 1e12. Artursson, P., Karlsson, J., 1991. Correlation between oral drug absorption in humans and apparent drug permeability coefficients in human intestinal epithelial (Caco-2) cells. Biochemical and Biophysical Research Communications 175 (3), 880e885. Arvanitoyannis, I.S., Choreftaki, S., Tserkezou, P., 2005. An update of EU legislation (directives and regulations) on food-related issues (safety, hygiene, packaging, technology, GMOs, additives, radiation, labelling): presentation and comments. International Journal of Food Science and Technology 40 (10), 1021e1112. Averina, E.S., Seewald, G., M€ uller, R.H., Radnaeva, L.D., Popov, D.V., 2010. Nanostructured lipid carriers (NLC) on the basis of Siberian pine (Pinus sibirica) seed oil. Die Pharmazie 65 (1). Batista, A.P., Portugal, C.A.M., Sousa, I., Crespo, J.G., Raymundo, A., 2005. Accessing gelling ability of vegetable proteins using rheological and fluorescence techniques. International Journal of Biological Macromolecules 36 (3), 135e143. Baur, J.A., Sinclair, D.A., 2006. Therapeutic potential of resveratrol: the in vivo evidence. Nature Reviews Drug Discovery 5 (6), 493e506. Bengoechea, C., Peinado, I., McClements, D.J., 2011. Formation of protein nanoparticles by controlled heat treatment of lactoferrin: factors affecting particle characteristics. Food Hydrocolloids 25 (5), 1354e1360. Benito, P., Miller, D., 1998. Iron absorption and bioavailability: an updated review. Nutrition Research 18 (3), 581e603.

Nanostructured Systems to Increase Bioavailability of Food Ingredients

Bhushani, J.A., Karthik, P., Anandharamakrishnan, C., 2016. Nanoemulsion based delivery system for improved bioaccessibility and Caco-2 cell monolayer permeability of green tea catechins. Food Hydrocolloids 56, 372e382. Bourbon, A.I., Pinheiro, A.C., Carneiro-da-Cunha, M.G., Pereira, R.N., Cerqueira, M.A., Vicente, A.A., 2015. Development and characterization of lactoferrin-GMP nanohydrogels: evaluation of pH, ionic strength and temperature effect. Food Hydrocolloids 48, 292e300. Bourbon, A.I., Cerqueira, M.A., Vicente, A.A., 2016a. Encapsulation and controlled release of bioactive compounds in lactoferrin-glycomacropeptide nanohydrogels: curcumin and caffeine as model compounds. Journal of Food Engineering 180, 110e119. Bourbon, A.I., Pinheiro, A.C., Cerqueira, M.A., Vicente, A.A., 2016b. Influence of chitosan coating on protein-based nanohydrogels properties and in vitro gastric digestibility. Food Hydrocolloids 60, 109e118. Cal o, E., Khutoryanskiy, V.V., 2015. Biomedical applications of hydrogels: a review of patents and commercial products. European Polymer Journal 65, 252e267. Carvalho, A.G.S., Silva, V.M., Hubinger, M.D., 2014. Microencapsulation by spray drying of emulsified green coffee oil with two-layered membranes. Food Research International 61, 236e245. Carvalho, I.T., Estevinho, B.N., Santos, L., 2016. Application of microencapsulated essential oils in cosmetic and personal healthcare products - a review. International Journal of Cosmetic Science 38 (2), 109e119. Chen, L., Remondetto, G.E., Subirade, M., 2006. Food protein-based materials as nutraceutical delivery systems. Trends in Food Science and Technology 17 (5), 272e283. Chitkara, D., Nikalaje, S.K., Mittal, A., Chand, M., Kumar, N., 2012. Development of quercetin nanoformulation and in vivo evaluation using streptozotocin induced diabetic rat model. Drug Delivery and Translational Research 2 (2), 112e123. Conquer, J.A., Maiani, G., Azzini, E., Raguzzini, A., Holub, B.J., 1998. Supplementation with quercetin markedly increases plasma quercetin concentration without effect on selected risk factors for heart disease in healthy subjects. The Journal of Nutrition 128 (October 1997), 593e597. Das, J., Samadder, A., Mondal, J., Abraham, S.K., Khuda-Bukhsh, A.R., 2016. Nano-encapsulated chlorophyllin significantly delays progression of lung cancer both in in vitro and in vivo models through activation of mitochondrial signaling cascades and drug-DNA interaction. Environmental Toxicology and Pharmacology. Elsevier B.V. Dong, Z.J., Xia, S.Q., Hua, S., Hayat, K., Zhang, X.M., Xu, S.Y., 2008. Optimization of cross-linking parameters during production of transglutaminase-hardened spherical multinuclear microcapsules by complex coacervation. Colloids and Surfaces B: Biointerfaces 63 (1), 41e47. Dube, A., Nicolazzo, J.A., Larson, I., 2011. Chitosan nanoparticles enhance the plasma exposure of (-)-epigallocatechin gallate in mice through an enhancement in intestinal stability. European Journal of Pharmaceutical Sciences 44 (3), 422e426. Espitia, P.J.P., Du, W.X., de Jes us Avena-Bustillos, R., Soares, N.D.F.F., McHugh, T.H., 2014. Edible films from pectin: physical-mechanical and antimicrobial properties - a review. Food Hydrocolloids 35, 287e296. Falguera, V., Quintero, J.P., Jimenez, A., Mu~ noz, J.A., Ibarz, A., 2011. Edible films and coatings: structures, active functions and trends in their use. Trends in Food Science and Technology 22 (6), 292e303. Fathi, M., Mozafari, M.R., Mohebbi, M., 2012. Nanoencapsulation of food ingredients using lipid based delivery systems. Trends in Food Science and Technology 23 (1), 13e27. Feng, J., Wu, S., Wang, H., Liu, S., 2016. Improved bioavailability of curcumin in ovalbumin-dextran nanogels prepared by Maillard reaction. Journal of Functional Foods 27 (Suppl. C), 55e68. Fuci~ nos, C., Guerra, N.P., Teij on, J.M., Pastrana, L.M., R ua, M.L., Katime, I., 2012. Use of poly(N-isopropylacrylamide) nanohydrogels for the controlled release of pimaricin in active packaging. Journal of Food Science 77 (7), 21e28. Gao, Y., Li, Z., Sun, M., Li, H., Guo, C., Cui, J., et al., 2010. Preparation, characterization, pharmacokinetics, and tissue distribution of curcumin nanosuspension with TPGS as stabilizer. Drug Development and Industrial Pharmacy 36 (10), 1225e1234. Gasa-Falcon, A., Odriozola-Serrano, I., Oms-Oliu, G., Martín-Belloso, O., 2017. Influence of mandarin fiber addition on physico-chemical properties of nanoemulsions containing b-carotene under simulated gastrointestinal digestion conditions. LWT - Food Science and Technology 84, 331e337.

29

30

Nanomaterials for Food Applications

Gennadios, A., Hanna, M.A., Kurth, L.B., 1997. Application of edible coatings on meats, poultry and seafoods: a review. LWT - Food Science and Technology (Lebensmittel-Wissenschaft & Technologie) 30 (4), 337e350. Gibbs, B.F., Kermasha, S., Alli, I., Mulligan, C.N., 1999. Encapsulation in the food industry: a review. International Journal of Food Sciences and Nutrition 50 (3). Gobbi, M., Re, F., Canovi, M., Beeg, M., Gregori, M., Sesana, S., et al., 2010. Lipid-based nanoparticles with high binding affinity for amyloid-b1-42 peptide. Biomaterials 31 (25), 6519e6529. G omez-Mascaraque, L.G., Casagrande Sipoli, C., de La Torre, L.G., L opez-Rubio, A., 2017. Microencapsulation structures based on protein-coated liposomes obtained through electrospraying for the stabilization and improved bioaccessibility of curcumin. Food Chemistry 233 (Suppl. C), 343e350. Hessien, M., Singh, N., Kim, C., Prouzet, E., 2011. Stability and tunability of O/W nanoemulsions prepared by phase inversion composition. Langmuir: The ACS Journal of Surfaces and Colloids 27 (6), 2299e2307. Hu, B., Ting, Y., Yang, X., Tang, W., Zeng, X., Huang, Q., 2012. Nanochemoprevention by encapsulation of ()-epigallocatechin-3-gallate with bioactive peptides/chitosan nanoparticles for enhancement of its bioavailability. Chemical Communications 48 (18), 2421. Jones, O.G., McClements, D.J., 2011. Recent progress in biopolymer nanoparticle and microparticle formation by heat-treating electrostatic protein-polysaccharide complexes. Advances in Colloid and Interface Science 167 (1e2), 49e62. Jun-xia, X., Hai-yan, Y., Jian, Y., 2011. Microencapsulation of sweet orange oil by complex coacervation with soybean protein isolate/gum Arabic. Food Chemistry 125 (4), 1267e1272. Kakkar, V., Singh, S., Singla, D., Kaur, I.P., 2011. Exploring solid lipid nanoparticles to enhance the oral bioavailability of curcumin. Molecular Nutrition and Food Research 55 (3), 495e503. Kamil, A., Smith, D.E., Blumberg, J.B., Astete, C., Sabliov, C., Oliver Chen, C.Y., 2016. Bioavailability and biodistribution of nanodelivered lutein. Food Chemistry 192, 915e923. Khalil, N.M., do Nascimento, T.C.F., Casa, D.M., Dalmolin, L.F., de Mattos, A.C., Hoss, I., et al., 2013. Pharmacokinetics of curcumin-loaded PLGA and PLGA-PEG blend nanoparticles after oral administration in rats. Colloids and Surfaces B: Biointerfaces 101, 353e360. Koo, S.Y., Mok, I.-K., Pan, C.-H., Kim, S.M., 2016. Preparation of fucoxanthin-loaded nanoparticles composed of casein and chitosan with improved fucoxanthin bioavailability. Journal of Agricultural and Food Chemistry 64 (49), 9428e9435. https://doi.org/10.1021/acs.jafc.6b04376. Kwon, S.H., Kim, S.Y., Ha, K.W., Kang, M.J., Huh, J.S., Im, T.J., et al., 2007. Pharmaceutical evaluation of genistein-loaded pluronic micelles for oral delivery. Archives of Pharmacal Research 30 (9), 1138e1143. Lambert, J.D., Yang, C.S., 2003. Cancer chemopreventive activity and bioavailability of tea and tea polyphenols. Mutation Research - Fundamental and Molecular Mechanisms of Mutagenesis 523e524, 201e208. Lee, M.J., Maliakal, P., Chen, L., Meng, X., Bondoc, F.Y., Prabhu, S., et al., 2002. Pharmacokinetics of tea catechins after ingestion of green tea and (-)-epigallocatechin-3-gallate by humans: formation of different metabolites and individual variability. Cancer Epidemiology Biomarkers and Prevention 11 (10), 1025e1032. Li, W., Yi, S., Wang, Z., Chen, S., Xin, S., Xie, J., Zhao, C., 2011. Self-nanoemulsifying drug delivery system of persimmon leaf extract: optimization and bioavailability studies. International Journal of Pharmaceutics 420 (1), 161e171. Li, M., Cui, J., Ngadi, M.O., Ma, Y., 2015. Absorption mechanism of whey-protein-delivered curcumin using Caco-2 cell monolayers. Food Chemistry 180, 48e54. Li, J., Hwang, I.C., Chen, X., Park, H.J., 2016. Effects of chitosan coating on curcumin loaded nanoemulsion: study on stability and in vitro digestibility. Food Hydrocolloids 60, 138e147. Liu, L., Tang, Y., Gao, C., Li, Y., Chen, S., Xiong, T., et al., 2014. Characterization and biodistribution in vivo of quercetin-loaded cationic nanostructured lipid carriers. Colloids and Surfaces B: Biointerfaces 115, 125e131. Livney, Y.D., 2015. Nanostructured delivery systems in food: latest developments and potential future directions. Current Opinion in Food Science 3, 125e135. https://doi.org/10.1016/ j.cofs.2015.06.010.

Nanostructured Systems to Increase Bioavailability of Food Ingredients

Lopez-Rubio, A., Gavara, R., Lagaron, J.M., 2006. Bioactive packaging: turning foods into healthier foods through biomaterials. Trends in Food Science and Technology 17 (10), 567e575. L ucio, M., 2016. Novel resveratrol nanodelivery systems based on lipid nanoparticles to enhance its oral bioavailability. (January 2013), 177e187. Luo, Y.F., Chen, D.W., Ren, L.X., Zhao, X.L., Qin, J., 2006. Solid lipid nanoparticles for enhancing vinpocetine’s oral bioavailability. Journal of Controlled Release 114 (1), 53e59. Ma, Z.H., Yu, D.G., Branford-White, C.J., Nie, H.L., Fan, Z.X., Zhu, L.M., 2009. Microencapsulation of tamoxifen: application to cotton fabric. Colloids and Surfaces B: Biointerfaces 69 (1), 85e90. Martins, A.F., Bueno, P.V.A., Almeida, E.A.M.S., Rodrigues, F.H.A., Rubira, A.F., Muniz, E.C., 2013. Characterization of N-trimethyl chitosan/alginate complexes and curcumin release. International Journal of Biological Macromolecules 57, 174e184. McClements, D.J., 2011. Edible nanoemulsions: fabrication, properties, and functional performance. Soft Matter 7 (6), 2297e2316. McClements, D.J., 2012. Advances in fabrication of emulsions with enhanced functionality using structural design principles. Current Opinion in Colloid and Interface Science 17 (5), 235e245. McHugh, T.H., 2000. Protein-lipid interactions in edible films and coatings. Die Nahrung 44 (3), 148e151. Mozafari, M.R., 2010. Nanoliposomes: preparation and analysis. Methods in Molecular Biology (Clifton, N.J.) 605. Muller, R.H., Mader, K., Gohla, S., 2000. Solid lipid nanoparticles (SLN) for controlled drug delivery - a review of the state of the art. European Journal of Pharmaceutics and Biopharmaceutics 50 (1), 161e177. M€ uller, R.H., Petersen, R.D., Hommoss, A., Pardeike, J., 2007. Nanostructured lipid carriers (NLC) in cosmetic dermal products. Advanced Drug Delivery Reviews 59 (6), 522e530. Oh, J.K., Lee, D.I., Park, J.M., 2009. Biopolymer-based microgels/nanogels for drug delivery applications. Progress in Polymer Science (Oxford) 34 (12), 1261e1282. Ozturk, B., Argin, S., Ozilgen, M., McClements, D.J., 2015. Nanoemulsion delivery systems for oil-soluble vitamins: influence of carrier oil type on lipid digestion and vitamin D3 bioaccessibility. Food Chemistry 187, 499e506. Pandita, D., Kumar, S., Poonia, N., Lather, V., 2014. Solid lipid nanoparticles enhance oral bioavailability of resveratrol, a natural polyphenol. Food Research International 62, 1165e1174. Patel, D., Sawant, K.K., 2007. Oral bioavailability enhancement of acyclovir by self-microemulsifying drug delivery systems (SMEDDS). Drug Development and Industrial Pharmacy 33 (12), 1318e1326. Pathakoti, K., Manubolu, M., Hwang, H.M., 2017. Nanostructures: current uses and future applications in food science. Journal of Food and Drug Analysis 25 (2), 245e253. Piazzini, V., Monteforte, E., Luceri, C., Bigagli, E., Bilia, A.R., Bergonzi, M.C., 2017. Nanoemulsion for improving solubility and permeability of vitex agnus-castus extract: formulation and in vitro evaluation using PAMPA and Caco-2 approaches. Drug Delivery 24 (1), 380e390. Qiu, Y., Park, K., 2012. Environment-sensitive hydrogels for drug delivery. Advanced Drug Delivery Reviews 64 (Suppl.), 49e60. Ranganathan, A., Hindupur, R., Vallikannan, B., 2016. Biocompatible lutein-polymer-lipid nanocapsules: acute and subacute toxicity and bioavailability in mice. Materials Science and Engineering: C 69, 1318e1327. Rao, J., McClements, D.J., 2011. Food-grade microemulsions, nanoemulsions and emulsions: fabrication from sucrose monopalmitate & lemon oil. Food Hydrocolloids 25 (6), 1413e1423. Rasti, B., Erfanian, A., Selamat, J., 2017. Novel nanoliposomal encapsulated omega-3 fatty acids and their applications in food. Food Chemistry 230, 690e696. Rodríguez, J., Martín, M.J., Ruiz, M.A., Clares, B., 2016. Current encapsulation strategies for bioactive oils: from alimentary to pharmaceutical perspectives. Food Research International 83, 41e59. Rojas-Gra€ u, M.A., Soliva-Fortuny, R., Martín-Belloso, O., 2009. Edible coatings to incorporate active ingredients to fresh-cut fruits: a review. Trends in Food Science and Technology 20 (10), 438e447. Sagalowicz, L., Leser, M.E., 2010. Delivery systems for liquid food products. Current Opinion in Colloid and Interface Science 15 (1e2), 61e72.

31

32

Nanomaterials for Food Applications

Salminen, H., Weiss, J., 2014. Electrostatic adsorption and stability of whey protein-pectin complexes on emulsion interfaces. Food Hydrocolloids 35, 410e419. Salvia-Trujillo, L., Qian, C., Martín-Belloso, O., McClements, D.J., 2013a. Influence of particle size on lipid digestion and b-carotene bioaccessibility in emulsions and nanoemulsions. Food Chemistry 141 (2). Salvia-Trujillo, L., Rojas-Gra€ u, M.A., Soliva-Fortuny, R., Martín-Belloso, O., 2013b. Effect of processing parameters on physicochemical characteristics of microfluidized lemongrass essential oil-alginate nanoemulsions. Food Hydrocolloids 30 (1), 401e407. Salvia-Trujillo, L., Rojas-Gra€ u, M.A., Soliva-Fortuny, R., Martín-Belloso, O., 2015. Use of antimicrobial nanoemulsions as edible coatings: impact on safety and quality attributes of fresh-cut Fuji apples. Postharvest Biology and Technology 105, 8e16. Salvia-Trujillo, L., Soliva-Fortuny, R., Rojas-Gra€ u, M.A., McClements, D.J., Martín-Belloso, O., 2017. Edible nanoemulsions as carriers of active ingredients: a review. Annual Review of Food Science and Technology 8 (1), 439e466. Santiago, L.G., Castro, G.R., 2016. Novel technologies for the encapsulation of bioactive food compounds. Current Opinion in Food Science 7, 78e85. Schmitt, C., Turgeon, S.L., 2011. Protein/polysaccharide complexes and coacervates in food systems. Advances in Colloid and Interface Science 167 (1e2), 63e70. Sharma, A., Madhunapantula, S.V., Robertson, G.P., 2012. Toxicological considerations when creating nanoparticle based drugs and drug delivery systems? Expert Opinion on Drug Metabolism and Toxicology 8 (1), 47e69. Smith, A., Giunta, B., Bickford, P.C., Fountain, M., Tan, J., Shytle, R.D., 2010. Nanolipidic particles improve the bioavailability and a-secretase inducing ability of epigallocatechin-3-gallate (EGCG) for the treatment of Alzheimer’s disease. International Journal of Pharmaceutics 389 (1e2), 207e212. Somchue, W., Sermsri, W., Shiowatana, J., Siripinyanond, A., 2009. Encapsulation of a-tocopherol in protein-based delivery particles. Food Research International 42 (8), 909e914. Sun, M., Nie, S., Pan, X., Zhang, R., Fan, Z., Wang, S., 2014. Quercetin-nanostructured lipid carriers: characteristics and anti-breast cancer activities in vitro. Colloids and Surfaces B: Biointerfaces 113, 15e24. Sun, Y., Xia, Z., Zheng, J., Qiu, P., Zhang, L., McClements, D.J., Xiao, H., 2015. Nanoemulsion-based delivery systems for nutraceuticals: influence of carrier oil type on bioavailability of pterostilbene. Journal of Functional Foods 13, 61e70. Surassmo, S., Min, S., Bejrapha, P., Choi, M., 2010. Effects of surfactants on the physical properties of capsicum oleoresin-loaded nanocapsules formulated through the emulsion e diffusion method. Food Research International 43 (1), 8e17. Tsai, Y.M., Jan, W.C., Chien, C.F., Lee, W.C., Lin, L.C., Tsai, T.H., 2011. Optimised nano-formulation on the bioavailability of hydrophobic polyphenol, curcumin, in freely-moving rats. Food Chemistry 127 (3), 918e925. Turgeon, S.L., Beaulieu, M., Schmitt, C., Sanchez, C., 2003. Protein-polysaccharide interactions: phaseordering kinetics, thermodynamic and structural aspects. Current Opinion in Colloid and Interface Science 8 (4e5), 401e414. Wang, R., Tian, Z., Chen, L., 2011. Nano-encapsulations liberated from barley protein microparticles for oral delivery of bioactive compounds. International Journal of Pharmaceutics 406 (1e2), 153e162. Warden, B.A., Smith, L.S., Beecher, G.R., Balentine, D.A., Clevidence, B.A., 2001. Catechins are bioavailable in men and women drinking black tea throughout the day. Journal of Nutrition 131 (6), 1731e1737. Wei, Y., Guo, J., Zheng, X., Wu, J., Zhou, Y., Yu, Y., et al., 2014. Preparation, pharmacokinetics and biodistribution of baicalin-loaded liposomes. International Journal of Nanomedicine 3623e3630. Weiss, J., Takhistov, P., McClements, D.J., 2006. Functional materials in food nanotechnology. Journal of Food Science 71 (9), 107e116. Wen, M.M., El-Salamouni, N.S., El-Refaie, W.M., Hazzah, H.A., Ali, M.M., Tosi, G., et al., 2017. Nanotechnology-based drug delivery systems for Alzheimer’s disease management: technical, industrial, and clinical challenges. Journal of Controlled Release 245, 95e107. Werle, M., Takeuchi, H., Bernkop-Schn€ urch, A., 2009. Modified chitosans for oral drug delivery. International Journal of Drug Development and Research 3 (2), 26e33.

Nanostructured Systems to Increase Bioavailability of Food Ingredients

Xia, Z., McClements, D.J., Xiao, H., 2015. Influence of physical state of b-carotene (crystallized versus solubilized) on bioaccessibility. Journal of Agricultural and Food Chemistry 63 (3), 990e997. Xie, X., Tao, Q., Zou, Y., Zhang, F., Guo, M., Wang, Y., et al., 2011. PLGA nanoparticles improve the oral bioavailability of curcumin in rats: characterizations and mechanisms. Journal of Agricultural and Food Chemistry 59 (17), 9280e9289. Yallapu, M.M., Jaggi, M., Chauhan, S.C., 2011. Design and engineering of nanogels for cancer treatment. Drug Discovery Today 16 (9e10), 457e463. Yang, S.B., Liu, C.M., Liu, W., Yu, H., Zheng, H.J., Zhou, W., Hu, Y., 2013a. Preparation and characterization of nanoliposomes entrapping medium-chain fatty acids and vitamin C by lyophilization. International Journal of Molecular Sciences 14 (10), 19763e19773. Yang, Z.Z., Zhang, Y.Q., Wang, Z.Z., Wu, K., Lou, J.N., Qi, X.R., 2013b. Enhanced brain distribution and pharmacodynamics of rivastigmine by liposomes following intranasal administration. International Journal of Pharmaceutics 452 (1e2), 344e354. Yee, S., 1997. In vitro permeability across Caco-2 cells (colonic) can predict In Vivo (small intestinal) absorption in man -Fact or Myth. Pharmaceutical Research 14 (6), 763e766. Yen, F.L., Wu, T.H., Lin, L.T., Cham, T.M., Lin, C.C., 2009. Naringenin-loaded nanoparticles improve the physicochemical properties and the hepatoprotective effects of naringenin in orally-administered rats with CCl4-induced acute liver failure. Pharmaceutical Research 26 (4), 893e902. Yi, J., Lam, T.I., Yokoyama, W., Cheng, L.W., Zhong, F., 2014. Controlled release of b-carotene in b-lactoglobulin-dextran- conjugated nanoparticles’ in vitro digestion and transport with caco-2 monolayers. Journal of Agricultural and Food Chemistry 62 (35), 8900e8907. Yi, J., Zhong, F., Zhang, Y., Yokoyama, W., Zhao, L., 2015. Effects of lipids on in vitro release and cellular uptake of b-carotene in nanoemulsion-based delivery systems. Journal of Agricultural and Food Chemistry 63 (50), 10831e10837. Yu, H., Huang, Q., 2012. Improving the oral bioavailability of curcumin using novel organogel-based nanoemulsions. Journal of Agricultural and Food Chemistry 60 (21), 5373e5379. Zeeb, B., Mi-Yeon, L., Gibis, M., Weiss, J., 2018. Growth phenomena in biopolymer complexes composed of heated WPI and pectin. Food Hydrocolloids 74, 53e61. Zhang, J., Lv, H., Jiang, K., Gao, Y., 2011. Enhanced bioavailability after oral and pulmonary administration of baicalein nanocrystal. International Journal of Pharmaceutics 420 (1), 180e188. Zhang, H.Y., Arab Tehrany, E., Kahn, C.J.F., Ponçot, M., Linder, M., Cleymand, F., 2012. Effects of nanoliposomes based on soya, rapeseed and fish lecithins on chitosan thin films designed for tissue engineering. Carbohydrate Polymers 88 (2), 618e627. Zhang, Y., He, S., Li, Y., Tang, H., 2017. The physical stability and digestibility of b-carotene in oil-in-water sodium caseinate nanoemulsion. Journal of Food Measurement and Characterization 11 (2), 864e871. Zhao, L., Wei, Y., Huang, Y., He, B., Zhou, Y., Fu, J., 2013. Nanoemulsion improves the oral bioavailability of baicalin in rats: in vitro and in vivo evaluation. International Journal of Nanomedicine 8, 3769e3779. Zou, L., Zheng, B., Zhang, R., Zhang, Z., Liu, W., Liu, C., et al., 2016. Enhancing the bioaccessibility of hydrophobic bioactive agents using mixed colloidal dispersions: curcumin-loaded zein nanoparticles plus digestible lipid nanoparticles. Food Research International 81 (Suppl. C), 74e82.

FURTHER READING Sankar, P., Gopal Telang, A., Kalaivanan, R., Karunakaran, V., Manikam, K., Sarkar, S.N., 2009. Effects of nanoparticle-encapsulated curcumin on arsenic-induced liver toxicity in rats. Environmental Toxicology 24 (3), 296e303.

33

This page intentionally left blank

CHAPTER 3

Nanoencapsulation: Techniques and Developments for Food Applications Elham Assadpour1, Seid Mahdi Jafari2 1

Department of Food Science and Technology, Baharan Institute of Higher Education, Gorgan, Iran; 2Department of Food Materials and Process Design Engineering, Gorgan University of Agricultural Sciences and Natural Resources, Gorgan, Iran

Contents 3.1 Introduction 3.2 Nanoencapsulation Versus Microencapsulation 3.3 Classification of Nanoencapsulation Techniques 3.3.1 Lipid-Based Techniques for Nanoencapsulation of Food Ingredients 3.3.2 Nature Inspired Nanocarriers for Nanoencapsulation of Food Ingredients 3.3.3 Nanoencapsulation of Food Ingredients Through Specially Designed Equipment 3.3.4 Nanoencapsulation of Food Ingredients Through Biopolymer Nanoparticles 3.3.5 Miscellaneous Nanoencapsulation Techniques for Food Ingredients 3.4 Gastrointestinal Fate and Bioavailability of Nanoencapsulated Food Components 3.5 Conclusion and Final Remarks References

35 36 37 40 44 45 48 52 53 53 55

3.1 INTRODUCTION At present, with increasing awareness of consumers and their concerns about processed foods along with the rising number of complicated diseases such as various types of cancer, food bioactive compounds, nutraceuticals, and functional foods are attracting considerable attention (Augustin and Hemar, 2009; Jafari and McClements, 2017; Katouzian and Jafari, 2016). In fact, people are demanding food products with ingredients that can promote their health and protect their wellbeing besides just providing nutrients. In our modern lifestyle, it is not common to have access to many of these bioactive nutrients in a normal diet, so an alternative could be adding them to our daily food products. However, processing and environmental conditions such as high temperatures, light, oxygen, pH, presence of other ingredients within the matrix, etc., can have unfavorable effects on these valuable nutrients (Borel and Sabliov, 2014; Gharibzahedi and Jafari, 2017b). Another important issue is the bioavailability of nutraceuticals: the ratio of an ingested bioactive compound that is uptaken by our cells and can effectively provide health-promoting properties. Food bioactive ingredients and nutraceuticals should

Nanomaterials for Food Applications ISBN 978-0-12-814130-4, https://doi.org/10.1016/B978-0-12-814130-4.00003-8

© 2019 Elsevier Inc. All rights reserved.

35

36

Nanomaterials for Food Applications

generally resist passage through the initial stages of the gastrointestinal tract (GIT), particularly the stomach, and be ideally released within the intestine where, after crossing the epithelial wall, it may reach the blood stream and eventually the target organs within the body (Livney, 2015; Jafari et al., 2017b). In this context, nanoencapsulation has emerged as a possible strategy to protect food bioactive ingredients and to provide delivery systems for nutraceuticals (Assadpour et al., 2017). In this chapter, after a brief overview of the main differences between nanoencapsulation and microencapsulation, different nanoencapsulation technologies applicable to food ingredients will be presented on a systematic classification. Then, the recent studies and developments on nanoencapsulation of different food bioactive ingredients will be discussed, including phenolic compounds and antioxidants, essential fatty acids and fish oil, minerals, natural food colors, flavors, natural antimicrobial agents and essential oils, and bioactive peptides and enzymes.

3.2 NANOENCAPSULATION VERSUS MICROENCAPSULATION In general, micro-/nanoencapsulation processes consist of embedding bioactive ingredients within micro-/nanosized capsules to protect them against deteriorating environmental conditions such as high temperatures, oxygen, light, pH variations, undesired interactions with other compounds, etc. (Yada et al., 2014; Jafari, 2017a). Besides, micro-/nanoencapsulation may allow controlled or targeted delivery of the loaded bioactive components to the desired location and with an appropriate rate through engineered design of the capsules and correct selection of the wall materials. For these reasons, these processes have been extensively studied in different research areas including food, pharmaceutical and cosmetics, and recently in agrochemicals and fisheries, among others. It is generally accepted that nanoencapsulation should result in carriers with a size below 1 mm (1000 nm), although according to some specific legislations, particularly in the pharmaceutical and cosmetic areas, their size should be lower than 100 nm to be considered as nanocapsules (Shin et al., 2015; Jafari, 2017b). But, what are the advantages of nanoencapsulation over traditional microencapsulation for food ingredients? The reality is that when the size of particles is reduced to the nanoscale, there is a dramatic increase in the surface-to-volume ratio, which provides many attractive and unique properties to the nanoparticles. For instance, by producing nanoscale emulsions, liposomes, protein particles, etc., more available active sites are exposed on the surface of these delivery systems, which would be very beneficial for their absorption through the mucus-adhering mechanism within the digestive system of the body (McClements, 2015; Esfanjani and Jafari, 2016; Katouzian et al., 2017). On the other hand, penetration of nanocapsules into the cells and through the membranes would be much easier compared to microcapsules. Moreover, this higher surface-to-volume ratio enhances

Nanoencapsulation: Techniques and Developments for Food Applications

the interaction of nanocarriers with enzymes, microorganisms, and other target agents such as receptors in tissue cells, which again results in higher efficiency of nanocapsules (Faridi Esfanjani et al., 2018). Production of bioactive-loaded nanocarriers is more complex than generating microcapsules, and more advanced and sophisticated technologies are needed for the preparation of nanodelivery systems (Rafiee et al., 2018). Also, characterization and analysis of nanoencapsulated ingredients requires the use of specialized, modern instruments (Livney, 2015; Jafari and Esfanjani, 2017).

3.3 CLASSIFICATION OF NANOENCAPSULATION TECHNIQUES Nanoencapsulation is an emerging field of research that has been the focus of many recent studies. Fig. 3.1 shows the trends of publications in this field from 2007 to 2018. It is necessary to mention that statistics for 2018 is still in progress and certainly it will increase by the end of this year. This figure clearly shows that the number of publications in nanoencapsulation had a 500% growth in the last 10 years. According to Jafari (2017a,b), we can classify nanoencapsulation technologies into five groups based on the main mechanism/ingredient used to make nanocapsules for the food industry. They include lipid-based techniques, nature-inspired techniques, specializedequipment techniques, biopolymer-based techniques, and other miscellaneous techniques as shown in Fig. 3.2. There could be some overlaps in this classification; for example, some biopolymers are applied in specialized equipment techniques, but this classification is based on the main mechanism of nanocapsule formation. Selection of an appropriate technology for the production of food bioactive-loaded nanocarriers depends on many factors such as desired release profile and delivery purposes, physicochemical properties of the final product, economic considerations, available equipment, technical knowledge, etc (Assadpour 4000 3500

Publications

3000 2500 2000 1500 1000 500 0

Year

Figure 3.1 Trend of nanoencapsulation-related publications in Scopus (accessed on 16/04/2018). The keywords applied for search were “nano” and “encapsulation/capsule/carrier/delivery/release/entrapment/emulsion/liposome/nanoencapsulation”.

37

38

Nanomaterials for Food Applications

Food NanoencapsulaƟon Techniques

1. Lipid-based nanocarriers

2. Nature-inspired nanocarriers

3. Special equipment-based nanocarriers

4. Biopolymerbased nanocarriers

5. Miscellaneous nanocarriers

Nano-emulsions

Caseins

Electrospinning

Single biopolymer nanocarriers

Nanocrystals

Nano-structured phospholipid carriers

Cyclodextrins

Electrospraying

Complexd biopolymer nanocarriers

Nano-structured surfactants

Nano-lipid carriers

Amylose

Nano-spray dryer

Nano-gels

Inorganic nanocarriers

Micro/nanofluidics

Nanotubes

Chemical polymer nanoparƟcles

Figure 3.2 A systematic classification of different nanoencapsulation technologies applicable to food bioactive ingredients and nutraceuticals.

and Jafari, 2018). Detailed information about various nanocarriers applicable to food bioactive ingredients and nutraceuticals is provided in Table 3.1. It is worth mentioning that nanocapsules are not necessarily spherical nanoparticles; different morphologies and structures of final nanocarriers can be achieved based on the applied materials/technologies, which are briefly outlined below: • Spherical nanocarriers: They could be in the form of nanocapsule or nanosphere. Nanospheres can be defined as matrix systems utilized for the uniform dispersal of bioactive components, whereas nanocapsules are vesicular systems where bioactive compounds are encapsulated within a cavity consisting of an inner liquid core which in turn is surrounded by a polymeric membrane. Also, from a physical point of view, these nanocarriers can be “liquid” such as those prepared with nanoemulsions, nanoliposomes, biopolymer nanoparticles, solid lipid nanoparticles, and cyclodextrins (CDs), or “solid” such as nanoparticles made with nano spray dryer, electrospraying, and nanocrystals. • Tubular nanocarriers: They should have at least one dimension in the nanoscale (usually their cross section in nanosized) to be considered nanocarriers, although their length could be higher than 1000 nm. Within this group, we can include nanofibers (produced by electrospinning), nanotubes (from certain proteins such as a-lactalbumin), nanofibrils (for instance from b-lactoglobulin), and nanohelix structures (such as those from amylose). Bioactive components can be embedded within their hollow cavity.

Nanoencapsulation: Techniques and Developments for Food Applications

Table 3.1 An overview of different nanocarriers for the food industry No. Main groups Techniques/nanocarriers Different strategies

1

Lipid-based nanocarriers

Nanoemulsions

2 3

4

Nanostructured phospholipid carriers

5 6 7 8 9 10 11 12 13 14 15 16 17

Nanolipid carriers

Nature-inspired nanocarriers

Special equipmentbased nanocarriers

Biopolymer-based nanocarriers

Caseins Cyclodextrins Amylose Electrospinning Electrospraying Nano spray dryer Micro/nanofluidics Single biopolymer nanocarriers

18 19 20 21 22 23 24 25 26 27

Complexed biopolymer nanocarriers Nanogels

Nanotubes Miscellaneous nanocarriers

Nanocrystals

Single emulsions: Oil in Water (O/W); Water in Oil (W/O) Double emulsions: W/O/W; O/W/O Structural emulsions: Single interface layer; Double interface layer Liposomes: Monolayer; Multilayer Phytosomes: Monolayer; Multilayer Structural liposomes/phytosomes: With coatings Solid Lipid Nanoparticles (SLNs) Nanostructured Lipid Carriers (NLCs) Smart Lipid Carriers Alpha, Beta, Gamma-caseins Alpha, Beta, Gammacyclodextrins Single helix; Double helix Single injection nozzle; Double injection

Protein nanoparticles made by desolvation Polysaccharide nanoparticles made by precipitation Protein þ Protein Polysaccharide þ Polysaccharide Protein þ Polysaccharide Hydrogels Organogels/Oleogels Mixed gels Protein nanotubes made with a-lactalbumin Bioactives within crystals Bioactive crystals within other nanocarriers Continued

39

40

Nanomaterials for Food Applications

Table 3.1 An overview of different nanocarriers for the food industrydcont'd No. Main groups Techniques/nanocarriers Different strategies

28

Chemical polymer nanoparticles

29 30 31 32 33 34 35

Nanostructured surfactants Inorganic nanocarriers

Nanocarriers made with chemical polymers such as poly-D,L-lactide (PLA), Polyg-glutamic acid (PGA), and poly-capro-lactone acid (PCA) Dendrimers Niosomes Cubosomes and hexosomes Magnetic nanoparticles Silica nanoparticles Carbon nanotubes Quantum dots Gold nanoparticles

A schematic representation of nanocarrier morphologies has been depicted in Fig. 3.3.

3.3.1 Lipid-Based Techniques for Nanoencapsulation of Food Ingredients Different categories of lipid-based nanocarriers have been reported and reviewed in the last decade for food bioactive ingredients (Katouzian et al., 2017). The main types that have been studied and developed in recent years include nanoemulsions, nanoliposomes, nanostructured lipid carriers, and solid lipid nanoparticles (Akhavan et al., 2018). Concerning nanoemulsions, there have been plenty of research efforts on their formulation, characterization and application in the food, pharmaceutical, and cosmetic industries. These nanocarriers can be applied for nanoencapsulation of hydrophilic or hydrophobic bioactive components in the form of simple nanoemulsions, multiple nanoemulsions, pickering nanoemulsions, nanoemulsion-filled gels, and so on (Jafari et al., 2017c). In simple nanoemulsions, the bioactive ingredient is entrapped within the dispersed phase that is itself stabilized through surfactants/biopolymers in the continuous phase (Jafari et al., 2015). In multiple nanoemulsions, first an initial simple nanoemulsion is fabricated with the core material loaded within its internal phase and in the next step, it will be dispersed in a second continuous phase so that there is one internal phase, one middle phase, and one external phase (Assadpour et al., 2016a; Esfanjani et al., 2015). If the core material is a hydrophilic ingredient, then it is necessary to prepare waterin-oil nanoemulsions or water-in-oil-in-water double nanoemulsions. Although for hydrophobic ingredients such as fat-soluble vitamins and carotenoids, it is essential to formulate oil-in-water nanoemulsions or oil-in-water-in-oil double nanoemulsions.

Polymeric membrane

(A)

Bioactives

Polymeric matrix

Nano-capsule

Nano-sphere

Bioactives

(B)

α-lactalbumin

Enzyme or acid hydrolysis

Hydrolyzed molecules

Nanotubes

Ca+2

Figure 3.3 Schematic representation of different nanocarriers for food ingredients and nutraceuticals. (A) Spherical nanocarriers: nanosphere (from nanogels, biopolymer nanoparticles, casein micelles, etc.) versus nanocapsule (from nanoemulsions, nanoliposomes, SLNs, NLCs, cyclodextrins, etc.); (B) Tubular nanocarriers: nanofibers (from electrospinning), nanohelix (from amylose), nanotube (from a-lactalbumin).

42

Nanomaterials for Food Applications

In general, nanoemulsions can be produced by low energy methods (including phase transition approaches) and high-energy methods (such as high-pressure homogenization and ultrasonication). Also, there are some other mechanical techniques for production of nanoemulsions, which do not need energy as much as high-energy methods; some of the well-known techniques in this group are membrane emulsification and microfluidics (Esfanjani et al., 2017; Mehrnia et al., 2017). Regarding nanoliposomes, they are applicable for both hydrophilic and hydrophobic food ingredients (Demirci et al., 2017). Liposomes have been studied for a long time and their nanosized version, i.e., “nanoliposomes”, has been introduced in recent years with the main difference being their size. Nanoliposomes are produced from phospholipids (mainly lecithin) through various techniques; the two main methods include: (1) thin layer hydration technique, which needs some cholesterol and conversion of the phospholipid solution into a thin layer through vacuum evaporation of the solvent; (2) noncholesterol technique, which eliminates usage of cholesterol by replacing it with solvents such as glycerol and heating in a water bath. After formation of the liposome structure, its size will be reduced to the nanoscale by applying high-energy devices such as ultrasonication (Ghorbanzade et al., 2017). The phospholipid vesicular nanocapsule can be single layered (unilamellar) or multilayered (multilamellar). In these nanocarriers, hydrophilic ingredients are entrapped within the polar cavity in the central part, and hydrophobic components can be encapsulated within the nonpolar layer at the peripheral of the resultant capsules. In recent years, there have been some studies on the stability improvement of nanoliposomes through application of an extra biopolymer layer (such as chitosan) on the external surface of liposomes, resulting in changes in the zeta potential of the prepared nanocarriers due to the inherent surface charges of these biopolymers (Demirci et al., 2017). Also, “nanophytosomes” are a new class of nanoliposomes that have been customized for entrapment of bioactive phytochemicals, particularly phenolic compounds (Esfanjani and Jafari, 2016). Although both of them have a similar structure, there are two main differences: (1) in phytosomes, there is 1:1 or 1:2 (phospholipid:bioactive) stoichiometry ratio, whereas in nanoliposomes this is much higher; (2) in nanoliposomes, the bioactive is entrapped physically, but in nanophytosomes, the bioactive will be bound chemically to the structure of the carrier, for example through hydrogen bonds, which makes it more stable. Finally, within this group, there is a new generation of nanocarriers that are generally called nanostructured lipid carriers (NLCs) (Katouzian et al., 2017). To control the release of bioactive ingredients and to give a better protection of the core material and reduce its leakage, scientists have developed solid lipid nanoparticles (SLNs). In fact, SLNs are similar to nanoemulsions, but the oil component in their dispersed phase is solidified (Pyo et al., 2017). This strategy allows reducing the leakage of the entrapped bioactive ingredient, enhancing its protection. But because of crystallization

Nanoencapsulation: Techniques and Developments for Food Applications

consequences of the solid lipid, researchers have optimized this technology by replacing the solid phase with a mixture of solideliquid lipid, developing the so-called NLCs (Pyo et al., 2017). NLCs and SLNs are appropriate for hydrophobic ingredients including some vitamins and many drugs. Their preparation methods are similar to those employed for nanoemulsions, with some modifications. An important step is the melting of the solid lipid before addition of the core material, which then solidifies in the form of SLNs or NLCs when mixed with a liquid oil. In Table 3.2, some examples of different food bioactive ingredients loaded within lipid-based nanocarriers are presented. Table 3.2 Some examples of different food bioactive ingredients loaded within lipid-based nanocarriers Nanoencapsulation Bioactive food Examples of the system ingredients bioactive Reference

Nanoemulsions

Nanoliposomes

Nanostructured lipid carriers

Phenolic compounds Essential fatty acids Vitamins

Catechins Fish oil Folic acid (B9)

Antimicrobial agents/ essential oils Natural colorants Flavors Minerals

Thymol, eugenol Crocin D-limonene C4H2FeO4

Phenolic compounds Essential fatty acids

Curcumin Fish oil

Vitamins Antimicrobial agents/ essential oils Natural colorants Flavors Minerals Phenolic compounds Essential fatty acids Vitamins

Vitamin B12 Nisin Astaxanthin Allicin FeSO4 Resveratrol Krill oil Vitamin E

Antimicrobial agents/ essential oils Natural colorants Minerals

Clove extract (eugenol) Anthocyanin FeSO4

Bhushani et al. (2016) Dey et al. (2012) Assadpour et al. (2016a,b) Ma et al. (2016) Mehrnia et al. (2016) Jafari et al. (2007) Tang and Sivakumar (2013) Mourtas et al. (2014) Ghorbanzadeh et al. (2017) Bochicchiu et al. (2016) Colas et al. (2007) Yoo et al. (2010) Lu et al. (2014) Hermida et al. (2011) Jose et al. (2014) Zhu et al. (2015) Uraiwan and Satirapipathkul (2016) Cortes-Rojas et al. (2014) Ravanfar et al. (2016) Hosny et al. (2015)

43

44

Nanomaterials for Food Applications

3.3.2 Nature Inspired Nanocarriers for Nanoencapsulation of Food Ingredients The idea of bioactives encapsulation using natural nanocarriers results from taking into account the nature-made functionalities of these nanoparticles (Esfanjani and Jafari, 2016). As an example, casein micelles can naturally encapsulate and transport vital nutrients through milk; amylose chains can bind a variety of flavor compounds developed during bread making, which can be released during subsequent heating, and starch derivatives (nanogranules and CDs) can form inclusion complexes with many nutraceuticals. Nature-inspired nanocarriers have received great attention for the delivery of nutrients and drugs because of their safety and low cost. The functional properties of naturally occurring nanovehicles are characterized by their biological source, isolation methods, or physical and biochemical alterations. These tiny natural nanoparticles such as caseins, CDs, amylose nanostructures, and starch granules are employed in the nanoencapsulation of bioactive food ingredients and nutraceuticals. Caseins are the major proteins of cow’s milk, accounting for 80% of its total protein content; caseins are found naturally in the form of spherical micelles with nanoparticles typically between 50 and 200 nm (Haratifar and Guri, 2017). Caseins have physicale chemical properties similar to copolymers with well-balanced hydrophobic and hydrophilic regions and can self-assemble to form nanosized carriers, with excellent thermal stability, offering enormous potential to be used as a natural carrier for bioactive food ingredients of hydrophobic or sensitive properties. In addition, the recent understanding of its physicochemical properties of each protein fractionation in casein micelle and the use of novel technologies have opened up new application opportunities. The way how caseins self-assemble into micelles due to hydrophobic and electrostatic interactions renders them very suitable for incorporation of hydrophobic active molecules (Esfanjani and Jafari, 2017). These protein assemblies are perfectly designed to transport all the essential nutrients from the mother to the offspring in the most precise way. Regarding the economical, nutritional, and safety issues, caseins have been proven to be one of the most reliable nanovehicles. All three types of caseins (as1, as2, and b-casein) have the ability to bind calcium, and calcium phosphate in their structure due to the presence of phosphate residues. Knowing this, researchers have looked at the possibility of utilizing caseins as carriers of other metal ions such as iron (Feþ2) and magnesium (Mgþ2) (Gharibzahedi and Jafari, 2017a). It is believed that the core of casein micelles provides an environment where nonpolar compounds could be accommodated for a safe delivery. Because of the structural and physicochemical characteristics and their ability for hydrophobic interactions, caseinates and b-caseins have been used to encapsulate different hydrophobic bioactive molecules such as hydrophobic vitamins, curcumin, fatty acids, etc. Cyclodextrins are hollow molecular nanocarriers with certain sizes to encapsulate many different ingredients through the insertion of the appropriate ‘‘guest’’ structure

Nanoencapsulation: Techniques and Developments for Food Applications

into their cavity (Gharibzahedi and Jafari, 2017). This cavity is less polar than water. The internal diameter of the water-insoluble cavity with a certain depth (0.78 nm) depends on the number of glucose units in a-, b-, and g-CDs, which is 0.57, 0.78, and 0.95 nm, respectively. Generally, the inclusion is formed by complexing one CD molecule and one guest molecule in a stoichiometry ratio of 1:1. However, it is possible in the design of CD complexes to include more than one guest with low and/or high molecular weights into the cavity (Gharibzahedi and Jafari, 2017). Starch, a widely available carbohydrate polymer, is the raw material for the industrial-scale production of CDs. These natural structures are formed through the transformation of starch by certain bacteria such as Bacillus macerans and Bacillus circulans through the CD-glycosyltransferase (CGTase) enzyme, which partially hydrolyzes starch into a-(C36H60O30), b-(C42H70O35), and g-(C45H80O40)eCDs. Modification of CDs not only can provide their safety, but also can keep the formation ability of inclusion complexes with different guest molecules (Asghari Ghajari et al., 2017). The modification usually converts natural CDs into their amorphous derivatives. Two primary chemical parameters including nucleophilicity of eOH groups and the production potential of complexes between CDs and applied reagents should be considered for their modification process. There are different methods involved in the complex formation between guest molecules and CDs such as dry mixing (physical blending), milling/cogrinding, kneading, coprecipitation, and so on (Gharibzahedi and Jafari, 2017a). In terms of amylose nanocarriers, different bioactive ingredients as ligands can be nanoencapsulated within amylose nanostructures (Zabar et al., 2009). The presence of ligands induces a conformational change in amylose, namely the conversion of double helices into a unit strand (V-shaped amylose), which is dense and has a central hydrophobic cavity, capable of binding lipophilic molecules such as fatty acids via hydrophobic interactions (Cohen et al., 2008). Some examples of different food bioactive ingredients loaded within nature-inspired nanocarriers are presented in Table 3.3.

3.3.3 Nanoencapsulation of Food Ingredients Through Specially Designed Equipment Many of the techniques that have been applied for nanoencapsulation of food ingredients rely on formulation knowledge and some well-known equipment such as rotorestator mixers, high-pressure homogenizers, ultrasonication devices, etc. But in the last few years, researchers throughout the world have developed specially designed equipment including nano spray dryer, electrospinning/spraying, and micro/nanofluidics for the direct production of nanoparticles and nanocarriers without any formulation background. Basically, an electrospinning assembly consists of three main elements (Ghorani et al., 2017), which are (1) a supply of high voltage, (2) a spinneret (typically made by

45

46

Nanomaterials for Food Applications

Table 3.3 Some examples of different food bioactive ingredients loaded within nature-inspired nanocarriers Nanoencapsulation Bioactive food Examples of the system ingredients bioactive Reference

Caseins

Phenolic compounds

Catechin

Essential fatty acids

Omega-3 docosahexaenoic acid (DHA) Folic acid (B9) Rosemary Extract

Vitamins Antimicrobial agents/ essential oils Natural colorants

Cyclodextrins

Amylose nanohelices

b-carotene

Haratifar and Corredig (2014) Zimet et al. (2011)

Penalva et al. (2015) Arranz et al. (2015)

Flavors Minerals Phenolic compounds

Lemon oil Iron succinylate Quercetin

Essential fatty acids

Salmon oil

Vitamins

Vitamin D3

Antimicrobial agents/ essential oils Natural colorants

a-Bisabolol Lycopene

Flavors

Menthol

Minerals Phenolic compounds Essential fatty acids Vitamins

C4H2FeO4 Genistin Linoleic acid Vitamin D3

Antimicrobial agents/ essential oils Natural colorants Flavors Minerals

Linalool

Saiz-Abajo et al. (2013) Sabik et al. (2014) Min et al. (2016) Borghetti et al. (2009) Hadaruga et al. (2016) Liu and Zhang (2016) Oliveira et al. (2017) Nerome et al. (2013) Ciobanu et al. (2013) Kapor et al. (2012) Cohen et al. (2008) Zabar et al. (2009) Hasanvand et al. (2015) Zhou et al. (2016)

b-Carotene Menthol CuSO4

Kim et al. (2013) Ades et al. (2012) Bashir et al. (2015)

repurposing a blunt hypodermic syringe), and (3) a grounded collector. A high voltage direct current supply is used to induce a surplus electric charge in the liquid polymer (either a melt, or more commonly a solution or dispersion). A fiber strand is pulled out of the droplet that is accelerated toward the collector. The liquid polymer is either pumped from the spinneret at a constant volume flow using a syringe pump or more

Nanoencapsulation: Techniques and Developments for Food Applications

traditionally fed from a reservoir at constant head (Jafari, 2017a). The resulting electrospun nanofibers can be applied to deliver bioactive components along with the fiberforming polymer; these bioactives significantly influence the mechanical properties and functionality of the nanofibers. Electrospun nanofibers are monofilaments, and if the fiber is being solidified in flight, it results in a cross section of cylindrical shape. When applying electrospinning for preparation of nanofibers containing bioactive components, it is necessary to consider different parameters such as the polymer solution properties, process variables, and ambient conditions because they influence the nanofiber structure and bead formation (Ghorani et al., 2017). Electrospraying is fundamentally similar to electrospinning, as both techniques are based on the same physics governing the ejection of a continuous stream; however, if the degree of molecular cohesion is below a critical level, droplets are formed from the ejecta, instead of a continuous fiber (Tapia-Hernandez et al., 2017). The theory of electrospraying technique is based on the ability of an electric field to crush a droplet into nanosized particles depending on the control parameters. It has been shown that nanoparticles obtained from electrospraying can serve as nanocarriers of bioactive components. Therefore, the electrospraying technique is a feasible method for the entrapment of nutraceutical compounds and for nanoencapsulation purposes (Jafari, 2017a). To obtain desired nanoparticles, the parameters that influence the morphology of the particles during electrospraying should be carefully controlled. These parameters can be classified in three groups: equipment, solution, and environmental factors (Tapia-Hernandez et al., 2017). Nano spray dryers have been introduced in the last few years to extend spray drying to the submicron scale (Arpagaus et al., 2018). Laboratory spray dryers are based on a fundamentally new concept of spray drying technology, involving the fabrication of submicron particles from a solution, nanoemulsion, or nanosuspension. To produce nanoscale particles via spray drying technology, some modifications on the experimental setup of traditional spray dryers have been necessary. A major constraint is the limited efficiency of separation and collection of submicron particles by cyclone separators. Typical cyclones are unable to collect particles below 2 mm (Arpagaus et al., 2017). In other words, submicron-sized particles cannot be collected using traditional spray dryers. The only feasible option for collection of nanoparticles is to use electrostatic particle collectors. Another limitation is the turbulent gas flow in the drying chamber, which results in particle depositions on the chamber wall. Furthermore, traditional atomizers do not allow the fine droplets being generated to reach submicron particle sizes. With the recent advances in nano spray dryer technology, particles > 1, that is, for a large particle with a thin electric double layer, where a is the radius of the particle and k is the Debye parameter. When ka