Recent advances in the production and application of nano-enabled bioactive food ingredients

Journal Pre-proof Recent advances in the production and application of nano-enabled bioactive food ingredients David Julian McClements

PII:

S2214-7993(20)30015-1

DOI:

https://doi.org/10.1016/j.cofs.2020.02.004

Reference:

COFS 555

To appear in:

Current Opinion in Food Science

Please cite this article as: McClements DJ, Recent advances in the production and application of nano-enabled bioactive food ingredients, Current Opinion in Food Science (2020), doi: https://doi.org/10.1016/j.cofs.2020.02.004

This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. © 2019 Published by Elsevier.

Recent advances in the production and application of nanoenabled bioactive food ingredients David Julian McClements*1,2 Department of Food Science, University of Massachusetts, Amherst, MA 01003

2

Department of Food Science & Bioengineering, Zhejiang Gongshang University, 18 Xuezheng

of

1

Street, Hangzhou, Zhejiang 310018, China

ro

Journal: Current Opinion in Food Science

-p

Due: February, 2020 Submitted:

re

Contact Information: David Julian McClements, Department of Food Science, University

413 545 2275.

Jo

ur na

Graphical Abstract

lP

of Massachusetts Amherst, Amherst, MA 01003, USA. [email protected]; Tel:

1

of ro -p re lP

Highlights

There have been rapid advances in edible colloidal delivery systems (CDS) for bioactives



Bioactive-loaded CDS are being fabricated from natural plant-based ingredients



CDS containing multiple bioactives may be suitable for personalized nutrition

ur na



applications 

CDS are finding increasing utilization in commercial food and beverage products

Jo

Abstract

Nanotechnology has been employed for the creation of structured colloidal delivery systems

that enhance the performance of functional food ingredients, such as vitamins, minerals, nutraceuticals, antimicrobials, antioxidants, colors, and flavors. A successful colloidal delivery system must be specifically designed for the particular application, which depends on the nature of the functional ingredient and end product. Nanotechnology principles are being used to tailor the composition, size, shape, charge, and morphology of the colloidal particles utilized for this

2

purpose. This article provides an overview of some of the major developments in this area over the past few years. In particular, it focuses on recent advances in the design and fabrication of multiple-bioactive delivery systems, plant-based delivery systems, and delivery systems for specific food applications.

Keywords: nanoemulsions; bioactive agents; nanoparticles; structural design; nutraceuticals

of

Introduction

The past couple of decades has seen a surge in research activity in the development of edible

ro

colloidal delivery systems (CDS) to encapsulate macronutrients, micronutrients, nutraceuticals, and other functional ingredients [1]. As an example, a Web of Science (Clarivate Analytics)

-p

search in December 2019 using the keywords “food” and “delivery system” showed that there were only 44 publications and 378 citations in 2000, but 776 publications and 24,709 citations in

re

2018, with the publication and citation trajectory still rising rapidly. Researchers working in this area are trying to formulate CDS for a broad range of active substances, including bioactive

lP

lipids, minerals, vitamins, preservatives, colors, flavors, and nutraceuticals [1-5]. These delivery systems are being designed to overcome problems associated with incorporating these active substances into foods, or alternatively, to enhance their functional performance [5, 6]. For

ur na

instance, they are being designed to overcome low water-dispersibility, poor chemical stability, off-flavors, and limited bioavailability of active substances, or to create targeted, triggered, or controlled release profiles [7].

In this review article, I focus on a number of recent trends in the development and application of CDS that are pertinent to the food industry. First, there is an increasing trend

Jo

towards formulating delivery systems for specific food applications [8], so that successful commercial products can be developed. Second, there is a move towards constructing CDS entirely from plant-derived ingredients so that they can be utilized in plant-based foods and beverages [9]. Third, there has been interest in the creation of CDS that contain multiple bioactive substances, which may be useful for the development of personalized nutrition products tailored to the nutritional requirements of specific individuals [10]. The author

3

acknowledges that there are many other interesting developments in this rapidly evolving area, but it is not possible to cover them all within this short article.

Designing with a purpose Much of the early work on food-grade delivery systems focused on the fabrication and characterization of different kinds of colloidal particles, such as micelles, liposomes, droplets, nanoparticles, or microgels. The main aim of this work was to identify ingredients and fabrication methods that could be used to create colloidal particles, to characterize the properties

of

of the particles formed, and to establish the main factors impacting their properties. More

recently, there has been interest in designing CDS that can be used in commercial applications to

ro

address particular problems. For instance, the delivery by design (DbD) concept was recently introduced to rationalize the development of colloidal delivery systems for specific applications

-p

in the food industry [8]. The DbD approach outlines a series of steps that need to be considered when developing a CDS: specifying the properties of the bioactive to be encapsulated; specifying

re

the properties of the end product; defining the desired particle characteristics; specifying the production process and testing protocol; and, optimizing the system. Ideally, cost effective food

lP

ingredients and processing operations should be developed that allow large-scale commercial production of the delivery system. Moreover, the CDS should not adversely impact the desirable sensory or physical properties of the end product, and it should remain stable throughout the

ur na

shelf life of the product.

The rational design of CDS for specific applications was recently demonstrated by a group of researchers from the Massachusetts Institute of Technology [11]. This group aimed to address the issue of malnutrition in developing countries, which arises from a lack of adequate quantities of bioavailable vitamins and minerals in their diet. The MIT group developed a microparticle-

Jo

based delivery system from a food-grade synthetic polymer (BMC). This polymer was selected because it was stable to boiling for prolonged periods (thereby retaining and protecting the micronutrients during cooking) and because it dissolved under gastric conditions (thereby releasing the micronutrients within the stomach). The researchers showed that 11 kinds of micronutrients normally lacking in the diet of the target populations could be encapsulated within separate microparticles or up to 4 different micronutrients could be encapsulated within the same microparticle. Encapsulation of the micronutrients was found to enhance their stability

4

to heating, light, moisture, and oxidation, and led to a relatively high bioavailability. The only potential drawback with the MIT study was the use of a synthetic polymer (BMC) to create the microparticles. There is a growing trend towards the use of more natural polymers, such as proteins and polysaccharides, but these may not always be able to mimic the functionality of synthetic polymers. The DbD approach has also been used to identify curcumin-loaded colloidal delivery systems that are suitable for incorporation into plant-based nutritional beverages [12]. A review

of

of the advantages and disadvantages of the various CDS available, such as micelles, liposomes, nanoemulsions, emulsions, solid lipid nanoparticles, and biopolymer particles, suggested that protein or lipid nanoparticles were the best option for this application. Curcumin-loaded protein

ro

nanoparticles can be assembled from hydrophobic plant proteins, such as zein and gliadin, using relatively simple methods, such as antisolvent precipitation [13-15]. The stability of these

-p

nanoparticles to changes in environmental conditions, such as pH, ionic strength, or temperature, can be enhanced by coating them with plant-based surfactants [16, 17] or biopolymers [15, 17].

re

Alternatively, curcumin can be encapsulated within the lipid nanoparticles in nanoemulsions stabilized by plant-based phospholipids, proteins, or polysaccharides [18-21]. The stability of

lP

this kind of bioactive-loaded nanoemulsion to environmental stresses can be improved by coating them with a layer of biopolymers, such as polypeptides or polysaccharides [22]. In the future, it will be important to utilize the findings from academic research to develop commercial

ur na

products, which has a number of unique challenges. For instance, the ingredients and processing operations used to formulate the CDS should be commercially viable, and the CDS must be compatible with the end product [8].

Plant-based Colloidal Delivery Systems

Jo

As mentioned earlier, one of the major trends in the modern food industry is the development of plant-based functional foods and beverages [23-25]. This often requires the reformulation of existing products to remove synthetic or animal-based ingredients and replace them with plant-based alternatives [9]. Consequently, there is considerable interest in the development of CDS that are assembled entirely from plant-based ingredients, such as oils, gelling agents, wall materials, thickeners, emulsifiers, preservatives, and other stabilizers. Plantbased hybrid nanoparticles that may be suitable as delivery systems have been fabricated from

5

plant proteins (wheat proteins) and phospholipids (soybean lecithin) [26]. These nanoparticles had a hydrophobic protein core surrounded by concentric phospholipid bilayers, and they were shown to exhibit good stability to pH changes (3-8), salt addition (0 to 300 mM), and heating (boiling). Plant-based nanoemulsions and emulsions have been prepared using a variety of plantderived emulsifiers, including saponins [27-30], phospholipids [31, 32], proteins [33-36], and polysaccharides [31, 37, 38]. Solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs) have also been formulated using plant-based emulsifiers to coat the lipid nanoparticles,

of

such as plant-derived saponins [39], phospholipids [40], and proteins [41]. The stability and functional performance of colloidal particles prepared from plant-based ingredients is highly dependent on the molecular and physicochemical properties of these ingredients. For instance,

ro

plant-based nanoemulsions stabilized with proteins are highly sensitive to flocculation near their isoelectric point, at high salt levels, or when they are heated, whereas those stabilized by

-p

polysaccharides are much more stable to these environmental stresses [31, 38]. The main reason for this difference is that protein-coated droplets are primarily stabilized by electrostatic

re

repulsion, whereas polysaccharide-coated ones are mainly stabilized by steric repulsion [31].

lP

Encapsulation of Multiple Bioactives in Colloidal Delivery Systems Traditionally, most researchers focused on incorporating a single bioactive substance into a colloidal delivery system, such as a specific vitamin into a nanoemulsion [42]. More recently,

ur na

there has been an increasing focus on the incorporation of multiple bioactive substances within CDS. A number of approaches can be used to achieve this goal, depending on the characteristics of the different bioactives to be encapsulated (Figure 1): 

Single phase systems: If the bioactives have similar polarities, then they can be located within the same phase in a colloidal delivery system. For instance, multiple hydrophobic

Jo

bioactives, like curcumin and piperine, can be encapsulated inside lipid or protein nanoparticles [43, 44]. Typically, the two hydrophobic bioactives would be mixed with the dispersed phase prior to particle formation.



Multiple phase systems: If the bioactives have different polarities, then they can be located within different phases in a colloidal delivery system, such as the oil, water, or interfacial phases. For instance, a hydrophobic bioactive can be encapsulated inside the lipid droplets of a nanoemulsion, whereas a hydrophilic bioactive can be dissolved in the

6

surrounding water. This approach has been used to create oil-in-water nanoemulsions containing oil-soluble bioactives (vitamin A or E) in the oil phase and water-soluble ones (vitamin C) in the water phase [45, 46]. The hydrophobic bioactives are typically mixed with the oil phase prior to homogenization, whereas the hydrophilic bioactives can be mixed with the water phase either before or after homogenization. 

Multiple particle systems: In some cases, it may be advantageous to encapsulate different bioactives within different colloidal particles, e.g., if the bioactives: (i) chemically react

of

with each other; (ii) have different solubility characteristics; (iii) have different stability requirements: or (iv) have different release requirements. This could be achieved using the same kind of delivery system for both bioactives or by using different kinds of

ro

delivery system for each bioactive. In the first instance, one bioactive could be

encapsulated within a nanoemulsion and then the other bioactive could be encapsulated in

-p

another nanoemulsion. A multiple-bioactive delivery system could then be assembled by mixing the two nanoemulsions together. In the second instance, one bioactive could be

re

encapsulated in a nanoemulsion, while another is encapsulated in a biopolymer nanoparticle or liposome. In these cases, it is important to ensure that the different kinds

lP

of colloidal particles are compatible with each other, and to ensure that the different kinds of bioactive agents do not migrate between the different kinds of colloidal particles. 

Hybrid systems: It is possible to create CDS containing multiple bioactive substances by

ur na

combining the above approaches. For example, a delivery system may contain two different hydrophobic bioactives within the oil phase, as well as one or more hydrophilic bioactive dispersed in the water phase.

Some recent specific examples of the development of CDS containing multiple bioactives

Jo

are given here. Epigallocatechin gallate (EGCG) and curcumin, which are both hydrophobic nutraceuticals, have been co-encapsulated within protein nanoparticles comprised of a hydrophobic zein core and an amphiphilic casein shell [47]. The presence of both nutraceuticals increased the antioxidant activity of the protein nanoparticles. Curcumin and quercetagetin have been encapsulated within hyaluronic-coated zein nanoparticles, which improved their stability to light or heat exposure [48]. Curcumin and piperine have been co-encapsulated inside polysaccharide-coated zein nanoparticles [43, 44]. Again, encapsulation was shown to improve

7

the light- and heat-stability of the bioactive agents. EGCG and quercetin have been coencapsulated inside liposomes, which was shown to synergistically enhance the antioxidant activity of the nutraceuticals [49]. These studies have demonstrated the potential of developing CDS for multiple bioactive agents. In future, this kind of delivery system may be useful for the creation of functional foods and beverages containing a specific blend of bioactives designed to meet the personalized nutrition requirements of a particular individual.

Conclusions and Future Directions

of

Nanotechnology principles have been employed by food and nutrition scientists to create a range of colloidal delivery systems suitable for application in the food and supplement areas.

ro

Much of the early work in this area was quite academic, with the primary aim of identifying

fabrication methods and ingredient combinations that could be used to create colloidal particles

-p

with specific properties. More recently, there has been a focus on applying these delivery systems within the food industry to solve particular problems. For instance, food-grade

re

nanoemulsions have recently been employed to encapsulate and control the release of cannabinoids (such as THC and CBD) in commercial edible products. In addition, they have

lP

been used to encapsulate and enhance the bioavailability of nutraceuticals in commercial functional foods and supplements. For industrial applications, it is important to construct colloidal delivery systems from ingredients and processing operations that are food-grade,

ur na

economic viable, and scalable, which is often a considerable challenge. As highlighted in this article, two of the most important directions in the future will be to create colloidal delivery systems entirely from sustainable plant-based ingredients, as well as to develop systems that can contain multiple bioactive agents for functional foods applications. Other areas where research will be important in the future is to develop commercially viable colloidal delivery systems that

Jo

can release their payloads at specific locations within the human gastrointestinal tract, such as the mouth, stomach, small intestine, or colon. The majority of the research in this area has focused on food applications, but there are a number of agriculture applications that are also important, such as the development of nano-pesticides or nano-fertilizers that are more effective than traditional versions.

8

Conflict of Interest The author declares no conflict of interest

Acknowledgements This material was partly based upon work supported by the National Institute of Food and Agriculture, USDA, Massachusetts Agricultural Experiment Station (MAS00491) and USDA,

Jo

ur na

lP

re

-p

ro

of

AFRI Grants (2016-08782).

9

References

Jo

ur na

lP

re

-p

ro

of

[1] Nowak E, Livney YD, Niu Z, Singh H. Delivery of bioactives in food for optimal efficacy: What inspirations and insights can be gained from pharmaceutics? Trends in Food Science & Technology. 2019;91:557-73. [2] Ali A, Ahmad U, Akhtar J, Badruddeen, Khan MM. Engineered nano scale formulation strategies to augment efficiency of nutraceuticals. Journal of Functional Foods. 2019;62. [3] Fathi M, Vincekovic M, Juric S, Viskic M, Jambrak AR, Donsi F. Food-Grade Colloidal Systems for the Delivery of Essential Oils. Food Reviews International. 2019. [4] Rezaei A, Fathi M, Jafari SM. Nanoencapsulation of hydrophobic and low-soluble food bioactive compounds within different nanocarriers. Food Hydrocolloids. 2019;88:146-62. [5] Rao J, Chen B, McClements DJ. Improving the Efficacy of Essential Oils as Antimicrobials in Foods: Mechanisms of Action. In: Doyle MP, McClements DJ, editors. Annual Review of Food Science and Technology, Vol 102019. p. 365-87. [6] Bao C, Jiang P, Chai J, Jiang Y, Li D, Bao W, et al. The delivery of sensitive food bioactive ingredients: Absorption mechanisms, influencing factors, encapsulation techniques and evaluation models. Food Research International. 2019;120:130-40. [7] McClements DJ. Recent progress in hydrogel delivery systems for improving nutraceutical bioavailability. Food Hydrocolloids. 2017;68:238-45. [8] McClements DJ. Delivery by Design (DbD): A Standardized Approach to the Development of Efficacious Nanoparticle- and Microparticle-Based Delivery Systems. Comprehensive Reviews in Food Science and Food Safety. 2018;17:200-19. [9] McClements DJ, Newman E, McClements IF. Plant-based Milks: A Review of the Science Underpinning Their Design, Fabrication, and Performance. Comprehensive Reviews in Food Science and Food Safety. 2019;18:2047-67. [10] Di Folco U, Pollakova D, De Falco D, Nardone MR, Tubili F, Tubili C. Effects of a nutraceutical multicompound including bergamot (Citrus Bergamia Risso) juice on metabolic syndrome: A pilot study. Mediterranean Journal of Nutrition and Metabolism. 2018;11:119-26. [11] Anselmo AC, Xu X, Buerkli S, Zeng Y, Tang W, McHugh KJ, et al. A heat-stable microparticle platform for oral micronutrient delivery. Science Translational Medicine. 2019;11:eaaw3680. [12] Kharat M, McClements DJ. Recent advances in colloidal delivery systems for nutraceuticals: A case study - Delivery by Design of curcumin. Journal of Colloid and Interface Science. 2019;557:506-18. [13] Wang Y, Yan W, Li R, Jia X, Cheng Y. Impact of deamidation on gliadin-based nanoparticle formation and curcumin encapsulation. Journal of Food Engineering. 2019;260:309. [14] Chuacharoen T, Sabliov CM. Comparative effects of curcumin when delivered in a nanoemulsion or nanoparticle form for food applications: Study on stability and lipid oxidation inhibition. Lwt-Food Science and Technology. 2019;113. [15] Liu Q, Jing Y, Han C, Zhang H, Tian Y. Encapsulation of curcumin in zein/ caseinate/sodium alginate nanoparticles with improved physicochemical and controlled release properties. Food Hydrocolloids. 2019;93:432-42. [16] Dai L, Zhou HL, Wei Y, Gao YX, McClements DJ. Curcumin encapsulation in zeinrhamnolipid composite nanoparticles using a pH-driven method. Food Hydrocolloids. 2019;93:342-50.

10

Jo

ur na

lP

re

-p

ro

of

[17] Zhang YQ, Wang B, Wu Y, Gao BY, Yu LL. Fabrication and Characterization of Zein Composite Particles Coated by Caseinate-Pectin Electrostatic Complexes with Improved Structural Stability in Acidic Aqueous Environments. Molecules. 2019;24. [18] Paez-Hernandez G, Mondragon-Cortez P, Espinosa-Andrews H. Developing curcumin nanoemulsions by high-intensity methods: Impact of ultrasonication and microfluidization parameters. Lwt-Food Science and Technology. 2019;111:291-300. [19] Shen PY, Zhang RJ, McClements DJ, Park Y. Nanoemulsion-based delivery systems for testing nutraceutical efficacy using Caenorhabditis elegans: Demonstration of curcumin bioaccumulation and body-fat reduction. Food Research International. 2019;120:157-66. [20] Ma PH, Zeng QH, Tai KD, He XY, Yao YY, Hong XF, et al. Development of stable curcumin nanoemulsions: effects of emulsifier type and surfactant-to-oil ratios. Journal of Food Science and Technology-Mysore. 2018;55:3485-97. [21] Ma PH, Zeng QH, Tai KD, He XY, Yao YY, Hong XF, et al. Preparation of curcuminloaded emulsion using high pressure homogenization: Impact of oil phase and concentration on physicochemical stability. Lwt-Food Science and Technology. 2017;84:34-46. [22] Carpenter J, George S, Saharan VK. Curcumin Encapsulation in Multilayer Oil-in-Water Emulsion: Synthesis Using Ultrasonication and Studies on Stability and Antioxidant and Release Activities. Langmuir. 2019;35:10866-76. [23] McClements DJ, Bai L, Chung C. Recent Advances in the Utilization of Natural Emulsifiers to Form and Stabilize Emulsions. In: Doyle MP, Klaenhammer TR, editors. Annual Review of Food Science and Technology, Vol 82017. p. 205-36. [24] Kapinova A, Stefanicka P, Kubatka P, Zubor P, Uramova S, Kello M, et al. Are plant-based functional foods better choice against cancer than single phytochemicals? A critical review of current breast cancer research. Biomedicine & Pharmacotherapy. 2017;96:1465-77. [25] Ribas-Agusti A, Martin-Belloso O, Soliva-Fortuny R, Elez-Martinez P. Food processing strategies to enhance phenolic compounds bioaccessibility and bioavailability in plant-based foods. Critical Reviews in Food Science and Nutrition. 2018;58:2531-48. [26] Chen X, Chen Y, Zou LQ, Zhang XC, Dong YQ, Tang JZ, et al. Plant-Based Nanoparticles Prepared from Proteins and Phospholipids Consisting of a Core Multilayer-Shell Structure: Fabrication, Stability, and Foamability. Journal of Agricultural and Food Chemistry. 2019;67:6574-84. [27] Doost AS, Van Camp J, Dewettinck K, Van der Meeren P. Production of thymol nanoemulsions stabilized using Quillaja Saponin as a biosurfactant: Antioxidant activity enhancement. Food Chemistry. 2019;293:134-43. [28] Nejatian M, Abbasi S. Formation of concentrated triglyceride nanoemulsions and nanogels: natural emulsifiers and high power ultrasound. Rsc Advances. 2019;9:28330-44. [29] Riquelme N, Zuniga RN, Arancibia C. Physical stability of nanoemulsions with emulsifier mixtures: Replacement of tween 80 with quillaja saponin. Lwt-Food Science and Technology. 2019;111:760-6. [30] Zhu Z, Wen Y, Yi J, Cao Y, Liu F, McClements DJ. Comparison of natural and synthetic surfactants at forming and stabilizing nanoemulsions: Tea saponin, Quillaja saponin, and Tween 80. Journal of Colloid and Interface Science. 2019;536:80-7. [31] Bai L, Huan S, Gu J, McClements DJ. Fabrication of oil-in-water nanoemulsions by dualchannel microfluidization using natural emulsifiers: Saponins, phospholipids, proteins, and polysaccharides. Food Hydrocolloids. 2016;61:703-11.

11

Jo

ur na

lP

re

-p

ro

of

[32] Akbas E, Soyler UB, Oztop MH. Capsaicin emulsions: Formulation and characterization. Journal of Dispersion Science and Technology. 2017;38:1079-86. [33] Li Y, Wu CL, Liu J, Zhu Y, Zhang XY, Jiang LZ, et al. Soy Protein IsolatePhosphatidylcholine Nanoemulsions Prepared Using High-Pressure Homogenization. Nanomaterials. 2018;8. [34] Jarzebski M, Fathordoobady F, Guo Y, Xu M, Singh A, Kitts DD, et al. Pea Protein for Hempseed Oil Nanoemulsion Stabilization. Molecules (Basel, Switzerland). 2019;24. [35] Tabilo-Munizaga G, Villalobos-Carvajal R, Herrera-Lavados C, Moreno-Osorio L, JarpaParra M, Perez-Won M. Physicochemical properties of high-pressure treated lentil protein-based nanoemulsions. Lwt-Food Science and Technology. 2019;101:590-8. [36] Li Y, Jin H, Sun X, Sun J, Liu C, Liu C, et al. Physicochemical Properties and Storage Stability of Food Protein-Stabilized Nanoemulsions. Nanomaterials. 2019;9. [37] Wu WY, Li L, Hong ZH, Xie XN. Comparison of emulsifying characteristics of different macromolecule emulsifiers and their effects on the physical properties of lycopene nanoemulsions. Journal of Dispersion Science and Technology. [38] Lv SS, Zhang YH, Tan HY, Zhang RJ, McClements DJ. Vitamin E Encapsulation within Oil-in-Water Emulsions: Impact of Emulsifier Type on Physicochemical Stability and Bioaccessibility. Journal of Agricultural and Food Chemistry. 2019;67:1521-9. [39] Kharat M, McClements DJ. Fabrication and characterization of nanostructured lipid carriers (NLC) using a plant-based emulsifier: Quillaja saponin. Food research international (Ottawa, Ont). 2019;126:108601-. [40] Trucillo P, Campardelli R. Production of solid lipid nanoparticles with a supercritical fluid assisted process. Journal of Supercritical Fluids. 2019;143:16-23. [41] Molina CV, Lima JG, Moraes ICF, Pinho SC. Physicochemical characterization and sensory evaluation of yogurts incorporated with beta-carotene-loaded solid lipid microparticles stabilized with hydrolyzed soy protein isolate. Food Science and Biotechnology. 2019;28:59-66. [42] Schoener AL, Zhang R, Lv S, Weiss J, McClements DJ. Fabrication of plant-based vitamin D-3-fortified nanoemulsions: influence of carrier oil type on vitamin bioaccessibility. Food & Function. 2019;10:1826-35. [43] Chen S, Li Q, McClements DJ, Han Y, Dai L, Mao L, et al. Co-delivery of curcumin and piperine in zein-carrageenan core-shell nanoparticles: Formation, structure, stability and in vitro gastrointestinal digestion. Food Hydrocolloids. 2020;99. [44] Chen S, McClements DJ, Jian L, Han Y, Dai L, Mao L, et al. Core-Shell Biopolymer Nanoparticles for Co-Delivery of Curcumin and Piperine: Sequential Electrostatic Deposition of Hyaluronic Acid and Chitosan Shells on the Zein Core. Acs Applied Materials & Interfaces. 2019;11:38103-15. [45] Hwang JY, Ha HK, Lee MR, Kim JW, Kim HJ, Lee WJ. Physicochemical Property and Oxidative Stability of Whey Protein Concentrate Multiple Nanoemulsion Containing Fish Oil. Journal of Food Science. 2017;82:437-44. [46] Kim TI, Kim TG, Lim DH, Kim SB, Park SM, Hur TY, et al. Preparation of Nanoemulsions of Vitamin A and C by Microfluidization: Efficacy on the Expression Pattern of Milk-Specific Proteins in MAC-T Cells. Molecules. 2019;24. [47] Yan X, Zhang X, McClements DJ, Zou L, Liu X, Liu F. Co-encapsulation of Epigallocatechin Gallate (EGCG) and Curcumin by Two Proteins-Based Nanoparticles: Role of EGCG. Journal of Agricultural and Food Chemistry. 2019;67:13228-36.

12

[48] Chen S, Han Y, Huang J, Dai L, Du J, McClements DJ, et al. Fabrication and Characterization of Layer-by-Layer Composite Nanoparticles Based on Zein and Hyaluronic Acid for Codelivery of Curcumin and Quercetagetin. Acs Applied Materials & Interfaces. 2019;11:16922-33. [49] Chen W, Zou M, Ma X, Lv R, Ding T, Liu D. Co-Encapsulation of EGCG and Quercetin in Liposomes for Optimum Antioxidant Activity. Journal of Food Science. 2019;84:111-20. Please note: The comments below will be moved into the final version at the end of review

of

** Nowak E, Livney YD 2019 – Highlights how knowledge developed in the pharmaceutical industry can be translated to the food industry to design more effective colloidal delivery

ro

systems.

* Chuacharoen and Sabliov 2019. – This recent article compares the effectiveness of

-p

nanoemulsions and protein nanoparticles at stabilizing curcumin from different environmental

re

stresses.

* Ma, Zeng, Tai et al 2018 – This article compares the efficacy of both synthetic (Tween 80) and

lP

natural (phospholipids, whey protein, and gum arabic) emulsifiers on the formation and stability of curcumin-loaded nanoemulsions. Although the synthetic surfactant performed the best,

examined.

ur na

nanoemulsions could also be made from the natural emulsifiers. The impact of oil type was also

** McClements 2018 – This article introduces the concept of delivery by design (DbD), which aims to make the creation of colloidal delivery systems for specific food applications more

Jo

commercially relevant.

* Li, Jin, Sun 2019 – This article compares the ability of a number of different plant-based proteins at forming nanoemulsions by sonication, including peanut, rice, and soybean proteins. It showed that stable nanoemulsions containing relatively small droplets (< 300 nm) could be produced from these proteins.

13

** Bai, Huan, Gu, … (2016). Comprehensive study of the impact of different natural emulsifiers on the formation and stability of food-grade nanoemulsions. Highlights the advantages and

Jo

ur na

lP

re

-p

ro

of

disadvantages of different plant-based emulsifiers for the formulation of nanoemulsions.

14

of ro -p re

Jo

ur na

delivery systems

lP

Figure 1. Examples of different approaches for creating multiple-bioactive loaded colloidal

15