Bioavailability of nanoparticles in nutrient and nutraceutical delivery

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Abstract

The field of nanoparticle delivery systems for nutrients and nutraceuticals with poor water solubility has been expanding, almost exponentially, over the last five years, and some of these technologies are now in the process of being incorporated in food products. The market projections for these technologies suggest a multifold increase in their commercial potential over the next five years. The interest in the pharmaceutical and food-related applications of these technologies has sparked tremendous developments in mechanical (top-down) and chemical (bottom-up) processes to obtain such nanoparticle systems. Mechanical approaches are capable of producing nanoparticles, typically in the 100–1000 nm range, whereas chemical methods tend to produce 10–100 nm particles. Despite these technological developments, there is a lack of information regarding the basis of design for such nanoparticle systems. Fundamental thermodynamic and mass transfer equations reveal that, in order to generate a broad spectrum delivery system, nanoparticles with 100 nm diameter (or less) should be produced. However, experimental data reveal that, in some cases, even nanoparticles in the 100–1000 nm range are capable of producing substantial improvement in the bioavailability of the active ingredients. In most cases, this improvement in bioavailability seems to be linked to the direct uptake of the nanoparticle. Furthermore, direct nanoparticle uptake is controlled by the size and surface chemistry of the nanoparticle system. The use of this direct nanoparticle uptake, in particular for soluble but poorly absorbed ingredients, is one of the areas that needs to be explored in the future, as well as the potential side effects of these nanoparticle carriers.

Introduction

The field of food nanotechnology has experienced significant growth over the last five years. Such growth has been fuelled by the potential of harnessing the large surface area to volume ratio of these materials to improve the bioavailability of active ingredients, introduce controlled/target release, improve sensory aspects, and others [1•], [2], [3•], [4•], [5]. The growth of the field is partially quantified in Fig. 1, where the cumulative number of articles and patents containing the keywords “food” and “nanoparticles” in their abstract or the claims (in the case of patents) is presented as a function of year of publication. As indicated by the trends in Fig. 1, most of the growth in the food nanotechnology field has taken place after the year 2000 as a result of numerous nanotechnology initiatives of the late nineties, and the development of food-grade additives suitable for nanoparticle production.

Currently, the market of nanotechnology products in the food industry approaches the US$ 1 billion (most of this on nanoparticle coatings for packaging technologies, health promoting products, and beverages) and has the potential to grow to more than US$20 billion in the next decade [1]. Recent reviews present an excellent summary of the research groups, private and government organizations that have been spearheading the field of food nanotechnology [1•], [4•]. Most of the work that these research groups have generated over the last five years on nanoparticle vehicles has concentrated on developing production methods inspired on pharmaceutical drug delivery systems [4••]. The challenge in developing such production methods has been to replace some of the polymers and surfactants used in the pharmaceutical industry with food-grade alternatives. Recent technological advances that make use of lipids, proteins and polysaccharides as additives are contributing to meet this challenge, and they have open the door to new functionalities and applications for nanoparticle delivery systems.

To design the next generation of nanoparticle vehicles it is necessary to reflect on the mechanisms of active ingredient uptake, and on how to modify or optimize the properties of these nanoparticles to maximize the bioavailability of different ingredients. The purpose of this review is to help fill, at least in part, that knowledge gap, and identify some of the elements that are still missing. Based on that information, new opportunities and challenges for nanoparticle vehicles will be discussed.

Section snippets

Nanoparticle vehicles in nutrient and nutraceutical delivery

There are two basic approaches to generate nanoparticle systems, one is the “top-down” approach, whereby small particles are produced through different size reduction (mechanical) processes, and the other approach is the “bottom-up” approach where the nanoparticle is produce by the self-assembly of smaller molecules such as lipids and proteins (chemical processes) [4•], [6], [7], [8], [9], [10], [11]. However, there is a growing trend to combine bottom-up and top-down approaches to produce

Bioavailability enhancement with nanoparticles

The term bioavailability refers to the fraction of a dose that is available at the site of action in the body. For most oral doses this definition is interpreted as the fraction of the dose that enters the bloodstream. Uptake (or intestinal absorption), on the other hand, refers to fraction of the dose that is absorbed through the intestinal walls. Although both definitions are related, the entire dose that is absorbed through the intestine (uptake) may not be bioavailable due to the various

Outlook

The field of food nanotechnology is experiencing significant growth due to the confluence of interests of industry, government and academia. In the area of nutrient and nutraceutical delivery there have been important advances made in nanoparticle formulations designed to improve the bioavailability of poorly water-soluble ingredients. However, very little has been done on the improvement of the uptake of hydrophilic compounds such as some soluble minerals (like calcium and iron) and soluble

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