Accepted Manuscript

Nanoencapsulation: An efficient technology to boost the antimicrobial potential of

plant essential oils in food system

Bhanu Prakash, Anupam Kujur, Amrita Yadav, Akshay Kumar, Prem Pratap Singh,
N.K. Dubey

PII: S0956-7135(18)30024-0
DOI: 10.1016/j.foodcont.2018.01.018
Reference: JFCO 5949

To appear in: Food Control

Please cite this article as: Bhanu Prakash, Anupam Kujur, Amrita Yadav, Akshay Kumar, Prem Pratap Singh, N.K.
Dubey, Nanoencapsulation: An efficient technology to boost the antimicrobial potential of plant essential oils in food
system, Food Control (2018), doi: 10.1016/j.foodcont.2018.01.018

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1 Nanoencapsulation: An efficient technology to boost the antimicrobial potential of plant 2

essential oils in food system

3 Authors: Bhanu Prakash*, Anupam Kujur, Amrita Yadav, Akshay Kumar, Prem Pratap

4 Singh and N. K. Dubey

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5 Centre for Advanced Study in Botany, Institute of Science, Banaras Hindu University, 6 Varanasi,

221005, India.

7 ∗Correspondance Tel.: +9794113055; 9482016540 E-mail addresses: bprakash@bhu.ac.in; 8

bhanubhu08@gmail.com

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26 Contents

27 1. Introduction

28 2. Plant essential oils as food preservatives: current status, challenges, and significance

29 2.1 Plants-essential oils as food preservatives: An outlook of recent study

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30 2.2 Challenges contributing to decline the use of plant essential oil as food preservatives 31 2.3

Renewal of the interest in the use of essential oils based food preservatives

32 3. Nanoencapsulation approaches to boost the antimicrobial potential of plants essential 33 oils:

From in vitro to food system

34 3.1 Nanocarrier as a delivery agent for plant essential oils in food system 35 3.2 Techniques used for

the characterization of encapsulated materials 36 4. Mechanism of action of nanoencapsulated plant

essential oil against food borne

37 microbes

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38 5. Nanotechnology in food industries: Perspective and challenges 39 6.

Concluding remarks

40 Acknowledgement

41 References
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47 Abstract:

48 Plant essential oils (EOs) possesses remarkable antimicrobial efficacy and therefore have 49 great

potential as an alternative of health hazardous synthetic preservatives. In spite of 50 marvellous

efficacy, their application yet not widely used by the food industries due to some

51 of the major intrinsic obstacles viz., low water solubility, bioavailability, volatility and

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52 stability in the food system. The recent advancement in nanotechnology has potential to 53 address

these existing obstacles of EOs as preservatives in the food system. The applications 54 of

nanomaterials as a carrier agent of EOs recently gain momentum of interest by the food 55 industries to

improve their shelf-life and preservatives efficacy at low doses. Nanoemulsions, 56 microemulsions,

solid-lipid nanoparticles and liposomes are some of the currently used 57 encapsulation strategies to

encapsulate plant bioactive compounds. In this review, we 58 explored the potential application of

nanoencapsulated plant EOs as novel source of food 59 preservatives. In addition, the prospects,

existing limitations and future research direction for

60 their commercialization are also discussed.

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61 Keywords: Antimicrobials, Essential oils, Food preservatives; Mode of action, 62 Nanotechnology.

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71 1. Introduction

72 The growing interest of consumers towards the green consumerism has resulted in the 73 use of

plant-derived natural products as an eco-friendly food preservative. Since most of the 74 currently used

synthetic preservatives are restricted to their use or under evaluation in view of

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75 resistance and adverse impact on the health and environment (Prakash & Kiran, 2016). 76 Therefore,

the food industries are currently looking towards some novel and safer approaches 77 for food

preservation to address the challenges to the existing synthetic preservatives. In this 78 context,

traditionally used EOs and their bioactive compounds possess inherent antimicrobial 79 activity against

food-born pathogen could offer a novel source for food preservation. Hence, 80 in past few decades, the

EOs and their bioactive compounds have been extensively studied 81 for their antimicrobial efficacy

against food borne pathogen viz., bacteria, molds and their 82 associated toxins. Some of the EOs and

their bioactive compounds viz., M

83 Mentha piperita, Pimenta officinalis, Matricaria chamomilla, Cuminum cyminum,
 84 Coriandrum sativum, Ocimum basilicum, carvacrol, carvone, cinnamaldehyde, citral, p

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85 cymene, eugenol, limonene, menthol, linalool, vanillin, citral and thymol have already been 86 listed

in Generally Recognised As Safe (GRAS) by the U.S. Code of Federal Regulations 87 (U.S. Code of

Federal Regulations, 2016). In spite of tremendous in vitro antimicrobial 88 efficacy, most of the EOs

fail to exert their full preservative potential in food system due to 89 some of the major intrinsic

obstacle viz., low water solubility, bioavailability, volatility, and 90 stability (Kujur, Kiran, Dubey, &

Prakash, 2017). The recent advances in nanotechnology 91 could successfully address these challenges

with controlled release of EOs to deliver their 92 boost effect at the right time and the right place. In

addition, nanomaterials (size < 100 nm) 93 can be used as a carrier to mask the undesirable aroma effect

of EOs and optimised their 94 interaction with food components (Donsi, Annunziata, Sessa, & Ferrari,

2011). The use of 95 nanomaterials as the delivery agent of EOs represents a promising approach to

improve the

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96 quality, safety and functionality of food products. Hence, application of nanotechnology in 97 the

food industry is one of the fastest growing fields in the past few years.

98 The review summarised the up-to-date account on the potential of EOs as food 99 preservatives. In

addition, the prospective application of nanotechnology, critical challenges

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100 and future perspective for the development of EOs based preservative have been discussed. 101 2.

Essential oils as food preservatives: current status, challenges, and significance

102 2.1. Essential oils as food preservatives: An outlook of recent study 103 The historical records
revealed that the EOs play a remarkable role in traditional 104 medicine. However, their application as a

food additive is the recent growing interest in view 105 of their strong antimicrobial and antioxidant

properties (Calo, Crandall, Bryan, & Ricke, 106 2015). The first scientific records about antimicrobial

efficacy of cinnamon oil against spores

107 of Anthrax bacilli were reported in the 1880s (Tajkarimi, Ibrahim, & Cliver, 2010). In M
108 general, EOs are the complex mixture of varied secondary metabolites viz., terpenes,

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109 terpenoids, phenylpropenes, aldehydes, ketones, ethers, and phenolics often showed strong 110

antimicrobial and antioxidant activity. Since the EOs are the complex mixture of compounds 111 their

application can effectively manage food born pathogen viz., bacteria, molds, and 112 associated toxins

without promoting the acquisition of resistance (Kavanaugh & Ribbeck, 113 2012; Prakash et al., 2012;

2013; 2014). Further, most of the EOs have low mammalian 114 toxicity and ephemeral in nature which

make them relatively safe for the health and 115 environment (Calo et al., 2015; Prakash & Kiran, 2016).

Therefore, in the past few decades, 116 EOs obtained from traditionally used aromatic plant families viz.,

Lamiaceae, Rutaceae, 117 Myrtaceae, Zingiberaceae, and Asteraceae have been extensively explored for

their efficacy 118 against food borne pathogen. The literature review studies over the past five year

revealed 119 that EOs and their bioactive compound exhibited strong efficacy against food born bacteria

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120 (Kavanaugh &Ribbeck, 2012;), molds (Kiran, Kujur, & Prakash, 2016; Prakash et al., 2013; 121

2014; 2015) and oxidative deterioration (Prakash et al., 2013; 2014; 2015; Kiran et al., 122 2016). The

list of some traditionally used EOs kept in GRAS category, their bioactivity and 123 elucidated major

compounds are summarised in Table 1.

124 2.2. Challenges contributing to decline the use of plant essential oil as food preservatives

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125 Although, a huge number of EOs and their bioactive compounds have been approved 126 by the

regulatory agencies such as European Commission and United States Food and Drug 127 Administration
 for their intended use as the flavouring agent in the food products (Hyldgaard, 128 Mygind, & Meyer,

2012). EOs have various intrinsic and extrinsic critical challenges which 129 hindered their application

as food preservatives. The scarcity of raw materials, chemotypic 130 variation, inconsistent efficacy, lack

of molecular mechanism of action, adverse impact on 131 food matrix, low water solubility, high cost

and threat of biodiversity losses are some of the

132 major challenges to EOs based preservatives (Prakash & Kiran, 2016). In addition, collection M
133 and identification of plants and quality assessment of raw materials need specialists who

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134 become increasingly rare (Bucar, Wube, & Schmid, 2013). Furthermore, quantity of EOs 135

obtained from the raw materials often insufficient for their commercial application. The 136 lipophilic

and volatile components of EOs are susceptible to polymerization and oxidative 137 deterioration during

storage that may change the functional composition of active 138 constituents as well as antimicrobial

properties (Turek & Stintzing, 2013). The food matrix 139 (fat, protein, carbohydrates, water activity,

salt contents and pH) together with extrinsic 140 factors such as temperature, gaseous composition, and

types of microorganisms could reduce 141 the antimicrobial potency of EOs (Gutierrez, Barry-Ryan, &

Bourke, 2008; 142 Rattanachaikunsopon & Phumkhachorn, 2010; Calo et al., 2015). In food system EOs

may 143 bind to lipids, proteins and carbohydrates, thus require high doses to achieve the 144

antimicrobial effect that may change the sensory threshold levels (Weiss, Loeffler, &

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145 Terjung, 2015). The intense aroma of most of EOs even at low dose may negatively influence 146

the organoleptic properties (flavour, color, taste and texture) of applicable food items leads to 147

decrease in consumer acceptance (Noori, Zeynali, & Almasi, 2018). Due to the 148 aforementioned

challenges, the interest in EOs based preservatives has been gradually

149 declining in past decade.

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150 2.3. Renewal of the interest in the use of essential oils based food preservatives 151 In view of

the recent consumer awareness towards safe and healthy food items with 152 minimal synthetic food

preservatives the global demands of plant-based food preservatives 153 increasing day by day. Further,
the recent reports on the suspected negative impact of some 154 of the currently used food preservatives

compelled the industries to look their sustainable 155 alternatives in the near future. For instance, the

food preservatives viz., propyl gallate, 156 butylated hydroxyanisole, (BHA), butylated hydroxytoluene

(BHT), tert-butylhydroquinone,

157 (TBHQ), nitrates, and nitrites have been reported to have potential increased risk for cancer. M
158 International Agency for Research on Cancer (IARC) classified butylated hydroxyanisole,

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159 (BHA) as class 2B carcinogen based on the sufficient evidence for its carcinogenicity in 160

experimental animals (IARC,1987). In this context, EOs of aromatic plants possess strong 161

antimicrobial and antioxidant potential could be used as natural preservatives to realize the 162 consumer

demand for safe, healthy and nutritious food (Prakash & Kiran, 2016). The recent 163 advancement in

modern science and technology viz., combinatorial chemistry, metabolomics, 164 and nanotechnology

generate new solutions for raw materials production and expanded the 165 application domain of EOs

and other natural products in food industries. Furthermore, the 166 recent advancement in extraction

techniques such as supercritical fluid extraction, microwave 167 ultrasonic-assisted extraction,

microwave steam distillation and steam diffusion etc., 168 enhanced the extraction yield and quality of

EOs (Bucar et al., 2013). Eco-SMART is one of 169 the world’s leading EO-based industries, that has

developed several bioactive formulation

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170 based on EOs and their bioactive compounds viz., Eugenol-Tween® and Eugenol 171 ethoxylate,

ActiVin™, Pycnogenol® and Herbalox® (Prakash & Kiran, 2016). The global 172 demands of safe

products are increasing day by day, and it is expected that the EOs market 173 will reach USD 11.67

billion by 2022(Grand View Research, 2015). Therefore, industries are

174 looking again towards the EOs for the formulation of plant-based food preservatives to

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175 address the resistance, health and other environmental issues related to synthetic 176 preservatives.
177 3. Nanoencapsulation approaches to boost the preservative potential of plant essential 178 oils:

From in vitro to food system

179 The concept of nanotechnology had been introduced by Richard Feynman (1959); 180 later on in

1974 Nario Taniguchi coined the term nanotechnology and used it for the 181 manipulation of particles

size less than one micrometer. It deals with the art of science to M
182 reduce the material size ranging from 1 to 100 nm which could be used as coating

183 material/carrier agent for the plant-based bioactive compounds. The reduction in particle size

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184 increases the surface-to-volume ratio which enhances their reactivity and offers many 185 unique

and novel features. In general, there are two hypotheses for the formulation of the 186 nanostructure of

different materials i.e. Top down and Bottom up techniques. The Top down 187 technique deals with the

nano-size range compounds produced from the larger size materials, 188 while in the case of Bottom up

techniques nano-size range material could be formed by self

189 assembly of atom by atom, molecule by molecule or atoms and molecules depends upon their 190

natural properties (Quintanilla-Carvajal et al., 2010). In the past few decades, nanotechnology 191 has

become a major focus of research activity in the field of pharma industry; while in the 192 food sector

this concept is a recent growing interest by the Industries as a delivery agent of 193 plant-based

preservative and nutraceuticals. Nanoencapsulation of EOs offers numerous 194 advantages such as ease

of handling, stability, protection against oxidation, enhanced

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195 distribution, solubility, controlled release, with less or no adverse effect on organoleptic 196

properties of applicable food items with enhanced bioavailability. Hence, the use of 197 nanotechnology

to develop EOs based preservatives could enhance their effectiveness in the 198 food system.

199 Donsi et al. (2011)reported that the nanoencapsulated volatile compounds (terpenes
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200 and D-limonene) exhibited enhanced antibacterial activity against food born bacteria viz., 201

Lactobacillus delbrueckii and Escherichia coli with minimal alteration of the organoleptic 202 properties

of treated food items. Jamil et al. (2016) studied the antimicrobial efficacy of 203 cardamom oil

encapsulated in chitosan-based nano-particles and reported that encapsulated 204 oil exhibit excellent

antimicrobial potential against Escherichia coli and Staphylococcus 205 aureus. Zandi, Rezaei, &

Farahmandghavi (2013) synthesised and characterised the chitosan 206 based nanoparticles as a carrier

agent for the oregano EO and recommend its use as

207 encapsulating material for the EOs based antimicrobials. Beyki et al. (2014) prepared M
208 chitosan-cinnamic acid nanogel as a carrier agent for Mentha piperita oil and studied their

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209 antimicrobial activity under sealed and non-sealed condition. They reported that encapsulated 210 oil

successfully retained its antimicrobial potential in non sealed condition. Hence, chitosan 211 based nano-

encapsulation could be used to reduce the evaporation rate of EOs during their 212 application in open

environment. Wu, Luo, & Wang (2012) prepared the nanoformulations of 213 thymol and carvacrol

using zein nanoparticles and reported that the encapsulation allows 214 better dispersion in water with

enhances activity against food-born pathogen and free radical 215 deterioration. Table 2 represent the

efficacy of encapsulated EOs and their bioactive 216 compounds against food borne pathogen.

217 3.1. Nanocarrier as a delivery agent for plant essential oils in food system: current 218 status

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219 Nanotechnology has become an increasingly important technology for food sector 220 especially to

boost the preservative potential of EOs. Encapsulating materials viz., chitosan 221 cyclodextrin, albumin,

globulin, maltodextrin, and starch, etc., have been used in the different 222 delivery systems to protect

EOs from intrinsic and extrinsic factors such as pH, water

223 activity, enzymatic degradation, temperature, relative humidity, and storage environment. A
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224 wide range of strategies has been proposed for the nano-formulation viz., polymeric 225

nanoparticles; solid-lipid nanoparticles and nanostructured lipid carriers; Liquid crystalline 226 systems,

nano/microemulsions, and liposomes. However, these methods have their own 227 limitations viz.,

physical and chemical stability, capsule compatibility, high cost of 228 production and the lack of food-

grade coating materials. Therefore, before the formulation or 229 synthesis of encapsulating material the

factors viz., polarity of active compounds, solubility, 230 volatility, availability and food matrix

composition must be taken into consideration. In

231 general, the EOs are the complex volatile mixture of lipophilic compounds; therefore, lipid M
232 based systems viz., nano and microemulsions, solid-lipid nanoparticles, and liposomes have

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233 been extensively studied to explore their efficacy as encapsulating materials for EOs based 234 food

preservatives. A systematic view of the preparation of different nanoformulation and 235 their expected

significance in food system has been presented in Figure 1.

236 Liposomes based strategies

237 Liposomes are the self-assembled spherical colloidal structure made up of 238 phospholipid bilayers

which enclose either aqueous or lipid soluble material (Zeisig & 239 Cammerer, 2001). The basis of the

liposome formation is the hydrophilic-hydrophobic 240 interaction between phospholipids and water-

soluble materials. Due to amphipathic nature, 241 the phospholipids have the ability to form a

membranous structure on dispersion in aqueous 242 solutions, their polar heads interact with the aqueous

environment, and long apolar aliphatic 243 chains interact with one another (Bozzuto& Molinari, 2015).

Owing to these properties they

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244 can be used as carrier agents for both lipophilic and hydrophilic molecules . (Atrooz, 2011; 245

Benech, Kheadr, Laridi, Lacroix, & Fliss, 2002). Depends on the preparation techniques and 246 layer

formation several groups of the liposomal system have been proposed viz., small 247 unilamellar
vesicles, large unilamellar vesicles, and multilamellar vesicles (Bozzuto &

248 Molinari, 2015). Valencia‐Sullca,, Jimenez, Jimenez, Atares, Vargas, & Chiralt (2016)

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249 prepared the antimicrobial film of eugenol and cinnamon leaf EO using lecithin liposomes 250 and

reported that liposome-based encapsulation exhibit improved film extensibility with 251 increased water

vapour barrier capacity over the uncapsulated compounds. Van Vuuren, du 252 Toit, Parry, Pillay, &

Choonara (2010) stated that the diastearoyl phosphatidylcholine and 253 diastearoyl

phosphatidylethanolamine liposomes could be used as the delivery agent of 254 Artemisia afra,

Eucalyptus globules, and Melaleuca alternifolia EOs to extend their shelf 255 life as an antimicrobial

agent. Detoni et al. (2012) prepared the liposome (multi and

256 unilamellar vesicle) based carrier agent for the Zanthoxylum tinguassuiba EO and reported M
257 that the carrier agent successfully enhanced the thermal stability and bioactivity of EO.

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258 Nanoemulsions based strategies

259 Emulsions system is one of the most widely used traditional technique in food 260 industries to

change the texture, flavour, and appearance of foods products viz., milk, cream, 261 mayonnaise,

beverages, and sauces, etc. It consists liquid-liquid dispersions of two 262 completely/partially

immiscible compounds in which one being dispersed in the form of 263 droplets to another one. To

improve the stability of emulsion system different suitable 264 emulsifiers are generally added which

encircle the dispersed droplets to reduce interfacial 265 tension or increase droplet-droplet repulsion

(Solans, Izquierdo, Nolla, Azemar, & Garcia

266 Celma, 2005; Tadros, Izquierdo, Esquena, & Solans, 2004). Due to the advent of modern 267

technology such as spontaneous emulsification and ultra-high-pressure homogenizers the 268 droplet size

of emulsion (oil/water/emulsifier) could reduce in the micro or nano-size range

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269 (<100 nm). Nanoemulsions exhibited better efficacy in term of appearance, stability, texture, 270 and
activity compared to the microemulsion. Donsi, Annunziata, Vincensi, & Ferrari (2012) 271 prepared

nanoemulsion containing EOs based compounds viz., carvacrol, limonene, and 272 cinnamaldehyde

using different emulsifier agents viz., lecithin, pea proteins, sugar ester,

273 Tween 20 and glycerol monooleate and studied their antimicrobial efficacy against

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274 Escherichia coli, Lactobacillus delbrueckii and Saccharomyces cerevisiae. The results 275 revealed

that the antimicrobial efficacy of nanoemulsion is influenced by the emulsifier 276 agent; hence, before

its use as carrier agent there is strict need of rational design to obtain the 277 desirable antimicrobial

effect in the food system. Almadiy, Nenaah, Al Assiuty, Moussa, & 278 Mira (2016) reported that the

nanoemulsions of Achillea biebersteinii, Achillea 279 fragrantissima, Achillea santolina and Achillea

millefolium exhibited enhanced antimicrobial 280 activity over the free oils against food-borne bacteria

staphylococcus aureus, Listeria

281 monocytogenes, Escherichia coli, Pseudomonas aeruginosa and Salmonella M

282 enteritidis.Therefore, currently, nanoemulsion-based encapsulation system gain momentum

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283 of interest to the food industries as carrier agent for EOs based preservatives.

284
285 Solid-lipid nanoparticles based strategies

286 Solid lipid nanoparticles are the colloidal carriers used as an alternative system to the 287 existing

traditional carriers such as emulsions, liposomes, and polymeric micro and 288 nanoparticles. It consists

biocompatible and biodegradable lipids which are in solid form at 289 room temperature. This system

has been widely used as a carrier agent for chemically 290 unstable hydrophobic compounds. It forms a

lipophilic matrix by homogenizing the oil and 291 water phase together along with the hydrophilic

emulsifier (Muller, Mader, & Gohla, 292 2000). Solid-lipid nanoparticles could greatly improve the

physical and chemical stability and 293 bioavailability of hydrophobic antimicrobials such as EOs and

their bioactive compounds 294 compared to liquid droplets/or conventional emulsion system (Shidhaye,

Vaidya, Sutar,

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295 Patwardhan, & Kadam, 2008). Lai, Wissing, Müller, & Fadda (2006) prepared two 296 different

solid-lipid nanoparticles as delivery agent of Artemisia arborescens EO using 297 Compritol 888 ATO,

Poloxamer 188 and Miranol Ultra C32. The results revealed that the 298 solid-lipid nanoparticles

exhibited high physical stability with reduce rate evaporation of

299 EOs.. Al-haj et al. (2010) reported that solid lipid nanoparticle containing Nigell sativa EO

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300 exhibited high physical stability up to three months and recommend its application as 301 suitable

carrier agent for EOs. Although this system of encapsulation has strong potential as 302 the carrier for

antimicrobial; the low loading capacity, chances of the expulsion of the coated 303 material are some of

the technical disadvantageous with this system. Therefore, currently, the 304 liquid lipids or mixture of

different lipids are used to create a matrix system to generate the 305 nanostructure lipid carriers for

antimicrobial EOs.

306 3.2 Techniques used for the characterization of encapsulated materials M

307 The particle size and surface area of encapsulating materials plays an important role

308 in controlling the release rate of EOs through the capsule core. Therefore, irreversible

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309 aggregation and chemical instability of nanoformulation must be avoided. Hence, it is 310 necessary

to convert the nanosuspensions into the solid form (Nakagawa, Surassmo, Min, & 311 Choi, 2011).

Currently, freeze drying and spray drying methods are employed for the drying 312 of nanosuspensions

to control and sustain the release rate of bioactive volatile compounds in 313 solid form. Lyophilization

or freeze drying technique is widely used in food industries to 314 remove the water vapour from the

nanoparticles. This process may negatively alter the 315 chemical properties of the coating material;

hence, the suitable cryoprotectant (Glucose, 316 mannose, maltose and trehalose) must be added to

preserve the overall quality. Contrary to 317 freeze drying, the spray-drying technique is rapid, cost
 effective and straightforward process 318 which can produce bulk amount at the commercial level. In

addition, spray drying leads to 319 the formation of spherical shaped particles; thereby provide a wider

surface area to the

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320 encapsulated core material. Therefore, in past few decades, it is widely used in food 321 industries to

encapsulate various food additives viz., flavors, vitamins, minerals, colorants, 322 and oils to extend their

shelf-life stability with enhanced functionality. Further, the 323 characterization of stable dried nano-

formulation is needed to speculate the positive or

324 negative impact of nanomaterials on the food system, health, and environment (Royal Society

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325 2004). Therefore, characterization of nanoparticles (chemical nature, aggregation, dispersion, 326

sorption, size, structure, and shape) should be done before their recommendation as an 327 antimicrobial

in the food system. Transmission electron microscopy (TEM) and scanning 328 electron microscopy

(SEM) are two widely used techniques to investigate the internal and 329 surface structure profile of

micro-and nanostructures respectively. Furthermore, the 330 spectroscopic technique viz., static light

scattering, dynamic light-scattering (DLS), neutron 331 scattering, small-angle neutron scattering,

nuclear magnetic resonance, and X-ray diffraction

332 (XRD) are some of the widely used to characterize the nanoformulation. M
333 4. Mechanism of action of nanoencapsulated plant essential oils against food borne

334 microbes

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335 Nanoencapsulated EOs and their bioactive compounds exhibiting strong antimicrobial 336 activity

could be used as safer alternative of synthetic ones (Donsi et al., 2012). Since, EOs 337 are the volatile

cocktail of several bioactive compounds (terpenes, terpenoids, 338 phenylpropenes and phenolics) that

may target different site at a time and disturb the 339 homeostasis of microbes, therefore, chance of

resistance development is negligible (Prakash, 340 Kedia, Mishra, & Dubey, 2015). The mechanism of

action of EOs depends on their inherent 341 biochemical profile and their ratio in crude EOs and it has a
cascade of reactions. In general, 342 EOs negatively interact with biochemical and structural attribute of

microbes lead to 343 disturbance of functioning of cell membrane, cytoplasm content, enzymes and

proteins 344 associated with normal functioning of cell, thereby, disturbed the microbial metabolism and

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345 lead to cell death (Donsi et al., 2012; Calo et al., 2015; Kujur et al., 2017). The nanomaterials 346

(chitosan, dextran, cellulose, starch, alginate and cyclodextrin etc.) used as carrier agents also 347

exhibits antimicrobial properties by the disruption of membrane potential, reactive oxygen 348 species

generation and altering the metabolic process (Alvarez-Paino, Munoz-Bonilla, &

Fernandez-Garcia, 2017). The small size (nano-range 10 -9 349 m) of nanoencapsulated EOs

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350 increases the surface area per volume unit; hence, they interact more efficiently with cell 351

membrane causing cell death at optimal doses (Gupta, Eral, Hatton, & Doyle, 2016). The 352 delivery

system is capable to transport the EOs across the cell membrane and then release the 353 EOs that may

act on inner side of cytoplasmic membrane (Donsi et al., 2012). In addition, 354 encapsulating materials

make shield between the EOs and food matrix, and deliver them at 355 specific targeted sites (water-rich

phases where the microorganisms preferentially proliferate) 356 with enhanced stability and

dispersability. Furthermore, the EOs may act synergistically with

357 the carrier agent posses antimicrobial activity, thereby enhanced the antimicrobial activity of M
358 nanoencapsulated EOs. Schematic representation of speculated mode of action of

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359 nanoencapsulated EOs in food matrix and their various targeted site is exemplified in Figure 360 2.

361 5. Nanotechnology in food industries: Perspective and challenges

362 Nanotechnology is an emerging area of food science and technology that holds great promise 363 in

food industry. The nano-particle size with large surface area gives distinctive feature to the 364

nanomaterials and makes them more effective and suitable in the food system. 365 Nanoencapsulated

antimicrobial (phytochemicals, alkaloids, EOs etc.) and antioxidants could 366 reduce the microbial
 contamination in the food system with enhanced organoleptic properties 367 (flavour, color, taste and

texture). A range of product based on nanotechnology is already 368 being used in different food sectors

viz., food processing, quality control, nutritional 369 supplements, antimicrobial and smart packaging

system (Chellaram et al., 2014). In view of

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370 promising results and applications, the use of nanotechnology can play remarkable role in the 371

development of programmable food, a futuristic concept promising the consumers to have 372 their food

of desired color, flavor, and nutrition (Ravichandran, 2010). Hence, the nano 373 technology may provide

innovative and economical development routes for food safety in the

374 near future.

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375 In spite of tremendous opportunity and potential, the application of the nano-based 376 product in the

food system is not fully approved by the regulatory authorities. Lack of 377 knowledge about the

potential unforeseen risks, consumers safety and ethical issues are some 378 of the major obstacles of

nanomaterials. The potential toxicological effects of nanomaterials 379 on biological system including

human health have so far not well studied (Donofrio, 2006). 380 Some of the recent studies revealed that

nanomaterials might impose the toxicological effects 381 on biological systems (Zhang, Xu, Bertrand,

Pridgen, Swami, & Farokhzad, 2012). Further,

382 the existing laws, safety testing methods are inadequate to measure the potential risks posed M
383 by the use of food exposed to nano-based chemicals. Keeping these point in view, a number

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384 of initiative have been taken to address the negative impact of nanomaterials on the health 385 and

environmental by the regulatory authorities such as Environment Protection Agency 386 (EPA), Food

and Drug Administration (FDA), UK Department for Environment, Food and 387 Rural Affairs and

nuclear protection agency etc., Therefore, there is strict need of further 388 research on toxicological

impact of nanomaterials into organism system before their wide 389 application as delivery agents of the

plant based preservative in food system.

390 6. Concluding remarks

 391 The global demand for safe and healthy food with minimal synthetic preservatives is 392 increasing

day by day especially by the health and environmentally concern consumers. In 393 this context, EOs

and their bioactive compounds possess strong antimicrobial activity could 394 play a remarkable role as a

novel source of food preservative.The use of modern scientific

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395 approaches viz., combinatorial chemistry, metabolic engineering and newer extraction 396 methods

have generated the novel source of raw materials with high yield thus expanded the 397 application

domain of EOs as antimicrobial agents. Further, the recent advancement in 398 nanotechnology offers

great opportunity to develop novel carrier agents for the delivery and

399 control release of EOs based preservatives in food system with enhanced chemical, oxidative

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400 and thermal stability. Although, nanoencapsulation is one of the promising tools for effective 401

delivery of EOs into food, the toxicological aspects of most of the nanocarriers and their 402 molecular

target site are yet poorly explored. Hence, the physiochemical interactions of 403 nanoencapsulated EOs

with food system and their toxicological impacts need to be 404 investigated before their commercial

application. Therefore, future research must be directed 405 towards the synthesis of novel synergistic

formulation based on EOs and their 406 nanoencapsulation to reduce the adverse effects on organoleptic

properties with improve

407 antimicrobial potency in the food matrix. 408 409

Conflict of interest:

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M
410 The authors declare that they have no conflict of interest.

411 Acknowledgement:

412 The authors acknowledge the financial support from the Science and Engineering 413 Research

Board (SERB), New Delhi, India, under Early Carrier Research Awards (Project 414 ECR/2016/000299).

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Highlights:

• Essential oils as food preservatives: current status, challenges and significance •

Nanoencapsulation approaches to boost the preservative potential of essential oils

• Nanocarrier and techniques used for the characterization of encapsulated materials

ANUSCRIPT
• Mechanism of action of nanoencapsulated essential oil against food borne microbes •

Critical challenges and prospects for their applications in the food industry

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