Engineered nano scale formulation strategies to augment efficiency of nutraceuticals

https://doi.org/10.1016/j.jff.2019.103554Get rights and content

Highlights

  • Nutraceuticals provide essential components to the body and prevent disease.

  • Nutraceuticals have limited aqueous solubility and bioavailability.

  • Nanotechnology ensures better efficiency of nutraceuticals than the traditional products.

  • Encapsulation of bioactives prevent them from g.i.t degradation.

  • Release of nutraceuticals is enhanced when delivered in nano sized form.

Abstract

Nutraceuticals have been widely explored for promoting health outcomes and in management of various diseases. They are considered to be neutral and safe and are extensively used to promote overall health. They play a vital role in modifying and maintaining normal body physiological functions. However, the bioactives present in nutraceuticals are unable to achieve their potential outcomes due to limited aqueous solubility leading to poor bioavailability profile and interaction with gastro-intestinal fluids. Majority of conventional products in market are unable to show their therapeutic outcome. Nanotechnology has tremendous potential to revolutionize the nutraceutical market. Recent progress in field of nutraceutical delivery has incorporated nanotechnology to overcome the drawbacks accompanying nutraceuticals. This review focuses on issues associated with nutraceuticals and various nanoscale formulation approaches like liposomes, nanoemulsions, nanocrystals, lipid and polymeric nanoparticles to obtain an insight to recent developments in nutraceuticals segment.

Introduction

Nanotechnology is moving out of the dominion of science fiction into our buildings, drugs, clothing, cosmetics, and even jolting into our foods, beverages, and dietary supplements. According to National Nanotechnology Initiative (NNI), nanotechnology has been broadly defined as the science and technology involved in the design, synthesis, characterization, and application of materials and devices with at least one of the dimensions on the nanoscale (usually in the range of 1–100 nm) (NNI, 2005). Nanotechnology has vast applications in food industry. It deals with size range of 10-9 m and at this size particles exhibit unique properties which changes the pharmacokinetics of the molecules and its subsequent effects.

A nutrient is anything that nourishes and is essential for a living being. The word nutrient has historical background and is derived from Latin word ‘nutrire’ meaning ‘to feed’, although the word first started out in 1965 as an adjective meaning ‘providing nourishment’. The term nutraceuticals means, “a food that has the required nutrient along with therapeutic effect.” The term nutraceuticals was first introduced by the chairperson and founder of “Foundation for Innovation in Medicine” by Mr. Stephen DeFelice in 1989 (Brower, 1998, Maddi et al., 2007).

Nutraceuticals are products that provide essential components to the body and prevent disease. It is a requirement beyond the basic nutrition which we get from our daily meals. It may comprise of dietary supplements, products of plant origin, nutrients that are isolated from mixture, genetically engineered food and products which are processed like beverages, cereals and soups, etc. (Dureja, Kaushik, & Kumar, 2003). At present a lot of conventional nutraceutical products are available in the market ranging from simple low cost products for daily use to high cost combinations prescribed in ailments. Population is spending more money on buying healthy and organic food in order to avoid illness which in turn is boosting the overall nutraceuticals market worldwide (Nelson, 1999). The global market of nutraceuticals was at US$165.62 billion in 2014. From 2015 to 2021 it is growing at a CAGR (Compound Annual Growth Rate) of 7.3% and by the end of 2021 the market is expected to reach US$278.96 billion according to the report published by transparency market research in September 2015 ((Nutraceuticals Product Market, 2015). Compound annual growth rate (CAGR) is a business and investing specific term for the geometric progression ratio that provides a constant rate of return over the time period. CAGR is not an accounting term, but it is often used to describe some element of the business, for example revenue, units delivered, registered users, etc. It is particularly useful to compare growth rates from various data sets of common domain such as revenue growth of companies in the same industry or sector. However, the problem with vast majority of these existing nutraceuticals is the lack of efficay in-vivo. These lipophilic compounds have been limited in their application to food system due to their extremely poor aqueous solubility, low oral bioavailability, g.i.t degradation, easy to oxidize, and immiscible feature with other major hydrophilic compounds (Ezhilarasi, Karthik, Chhanwal, & Anandharamakrishnan, 2013). According to the Biopharmaceutics Classification System (BCS) most functional foods could be classified into four different systems depending on their solubility and permeability. Most lipophilic components belong to class II or class IV in which low solubility is the major problem (Velikov & Pelan, 2008). Low solubility and poor adsorption of bioactive compounds would be also closely related to the low oral bioavailability due to lower stability of compounds and poor hepatic first pass metabolism (Oehlke et al., 2014, Patel and Velikov, 2011, Velikov and Pelan, 2008). Lipid-based delivery systems have been used to increase the bioavailability of BCS Class II drugs because they are broken down into mixed micelles in the small intestine, which increases the solubility of the drug in the intestinal fluids (Williams et al., 2013).

Nanotechnology’s application in nutrition and food industry is to fabricate or formulate food ingredients with novelty which has marked enhancement in its solubility, stability towards heat and light, better oral bioavailability and much pronounced physiological performance. Nano-carrier systems utilizes cores that may be liquid (emulsions and microemulsions), solid (solid lipid nanoparticles-SLNs), or a mix of solid and liquid domains (nanostructured lipid carriers-NLCs). Particles for encapsulation of hydrophilic ones are composed of an aqueous core, delineated from the surrounding continuous phase by a shell. These include nanohydrogels, liposomes and colloidosomes. In both categories, the nanocarriers are stabilized by either emulsifying molecules (emulsions) or by colloidal particles (Pickering emulsions) (Dan, 2016). All these have been widely exploited for effective delivery of lipophilic agents. Due to their extremely small size, nanocarriers have shown many advantages such as improvement of the aqueous solubility, enhancement of residence time in gastrointestinal (GI) tract regions, better physicochemical stability in GI tract, increase the intestinal permeation, controlled release in GI tract, intracellular delivery, and transcellular delivery (Oehlke et al., 2014).

So it becomes essential to design maps for a better nutraceutical industry by merging it with nanotechnology. Role of nutraceuticals can be more glorified by using nanotechnology which will definitely ensure better results than the traditional products available in the market. Owing to these nanotech advantages, an attempt has been made through this extensive review work to gain an insight or status of how engineered nanoscale formulation strategies are enabling effective delivery of nutraceuticals by minimizing their above mentioned limitations and improving the overall efficiency in-vivo.

Nutraceuticals could be classified into many types, however broadly they are categozied on the basis of food valaibility, chemical nature and mechanism of action of active component. These broad categories are further classified into various sub classes and are presented in Fig. 1.

Traditional Nutraceuticals are those which are obtained directly from nature and are used as such without any change in their form. Different constituents are available and used for various health related benefits like omega-3 fatty acid present in cod liver oil, saponin in soy, lycopene in tomatoes and its product etc. Traditional nutraceuticals can be futher divided into: (i) Nutraceutical enzymes (ii) Probiotic microorganisms (iii) Chemical Constituents (iv) Phytochemicals (v) Nutrients and (vi) Herbal

  • (i)

    Nutraceutical enzymes: Enzymes are biocatalyst which are proteinous in nature, specific in action and are produced by cells of body. Enzymes increases the rate of metabolic activity occuring inside the cells. Various problems can be treated by enzyme supplements like constipation, diarrhoea, GERD (gastroesophageal reflux disease), ulcerative colitis. Rare diseases like Hunter syndrome, Gaucher disease, Pompe disease, and Fabry disease can be treated by enzyme therapy. Diabetic patient could be treated with enzymes. From economical point of view microbial sources of enzyme are much preferred over plant and animal sources as they are much cheaper (Chanda, Tiwari, Kumar, & Singh, 2019).

  • (ii)

    Probiotic microorganisms: The term “Probiotic” was coined by Metchnikoff. The probiotic microorganisms has a vital position in medical field when it comes to process such as metabolism and absorption as it makes the intestine more favourable to these processes. Probiotics act by eradicating toxic flora that houses inside the intestine. For example useful consumption of Bacillus bulgaricus (Holzapfel, Haberer, Geisen, Björkroth, & Schillinger, 2001). Ailments of the human body can be treated by different probiotics product present in the market which has sufficient nutrient to fight various pathogen that causes discomfort in human body. The probiotics act by making the epithelial cells of the intestine more grounded thereby aiding the probiotics products for better retention, which is the need of the body. Probiotics are also helpful in people suffering from lactose intolerance as they help the sufferer by production of related enzyme ß-galactosidase which hydrolyzes lactose into its sugar components (Pineiro & Stanton, 2007).

On the basis of Chemical Constituent:

  • (i)

    Phytochemicals: Classification of this class is done on the basis of phytochemical present.

    • Flavonoids are secondary metabolites, present in many plants and has been clinically proven for preventing diseases like heart problems, diabetes, kidney problems by its antioxidant potential (Ehrlich, 2009).

    • Legumes like chickpeas and soybeans contains noncarotenoids which prevent cholesterol and has the potential to kill carcinogenic cells. Likewise anticancer activity property is also possessed by carotenoids which are present in vegetables. They also increases the immune system potential of an individual (Chanda et al., 2019).

    • Free radicals are produced as a product of metabolism of carbohydrate, fat, protein. These free radicals detoriates the cell of human body. One of the class of metabolites are the phenolic acid found in citrus fruits and red wine which has the property to destroy free radicals. This class of phytochemicals also has antitumor and anticancer property also (Chanda et al., 2019).

    • Classical example is of tumeric (curcumin), used as phytochemical in many kitchen (Chanda et al., 2019) and has antiinflammatory, antioxidant, wound healing, anticancer and many more properties.

  • (ii)

    Nutrient: Metabolic reactions occuring inside the human body are very much influenced by primary metabolite such as vitamins, amino acids, fatty acids as they have well defined functions to play in these metabolic reactions. Diseases related to heart, lung, kidney and other organs can be cured with product which are of plant and animal origin along with vitamin and may have several health benefit on the body. Maintenance of rhythm of heart muscles, transmission through neurons, providing strenght to bones and muscles, treating low heamoglobin count and many more ailments could be treated by natual products of plant and animal origin. For example reduction in cholesterol level in arteries and better functioning of the brain are well contributed effects of fatty acid, omega-3 PUFAs which is found in salmon.

  • (iii)

    Herbal: Many chronic disorder can be treated by the combination of herbal products with nurtraceutical. Antiarthritic, analgesic, astringent, antipyretic, anti-inflammatory properties are possessed by salicin found in willow bark (Salix nigra). Antipyretic, carminative, diuretic effect is shown by psoralen found in parsley (Petroselinum crispum) which falls under the category of flavonoids. Cold and flu can easily be cured by various terpenoids especially menthol, a bioactive constituent present in Peppermint (Mentha piperita). Relaxing stress, lowering blood pressure and treating lung disorder such asthma are some of the medicinal effect of tannin contents of lavender (Lavandula angustifolia) (Ehrlich, 2008).

Nontraditional Nutraceuticals: These are biotechnologically designed crops or food that that have much higher amount of nutrient when compared to normal crops or food. They can be classified as:

  • (i)

    Recombinant Nutraceuticals: Biotechnology tools have been well applied through a fermentation process in various food materials such as cheese and bread to extract the enzyme useful for providing necessary nutrients at an optimum level.

  • (ii)

    Fortified Nutraceuticals: In this type of nutraceutical compatible nutrients are added to the main ingredients such as flour fortified with calcium, milk fortified with cholecalciferol inorder to treat deficiency of vitamin D, minerals added to cereals, etc. (Casey, Slawson, & Neal, 2010). Detailed classification of nutraceuticals is represented in Fig. 1.

Section snippets

Problems associated with nutraceuticals:

Everything we eat has an impact on our life. The constituents present in food have ability to alter biological processes only if they are able to reach the systemic circulation. Majority of the constituents used in nutraceuticals are derived from natural sources and the common problems associated with them is low aqueous solubility and bioavailability.

Nanotechnology based systems as a tool for delivery of nutraceuticals components

Absorption of nutraceuticals is hindered due to their limited aqueous solubility. Researchers are putting in their hard effort to fabricate dosage form of nutraceuticals that retains its identity of providing health benefits without compromising its intestinal absorption. Products which are based on nanotechnology can easily solve this purpose. Some of the methods which can be utilized in delivery of nutraceuticals is depicted in Fig. 2 with their size in nanometer.

A delivery-system acts as a

Conclusion and future prospects

Challenges in nutraceuticals involve their high dose levels, inadequate consistency and reproducibility, characterization and solubility problems, formulation challenges, stability issues at least over two years, and manufacturing issues on large scale for high-quality products. Further, much needs to be accomplished using nanonutraceuticals of biotechnologically-developed, genetically-modified, and tissue cultured products, and to find ways and manners to prove the efficiency of these products

Ethical statement

This is a review work and does not contain experiments on animals

Declaration of Competing Interest

All the authors declare no conflict of interest

Acknowledgements

The authors are thankful to Honourable Chancellor, Integral University, Lucknow for providing the necessary resources for successful completion of this work.

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