Nutraceutical Concepts and Dextrin-Based Delivery Systems

Abstract

Nutraceuticals are bioactive or chemical compounds acclaimed for their valuable biological activities and health-promoting effects. The global community is faced with many health concerns such as cancers, cardiovascular and neurodegenerative diseases, diabetes, arthritis, osteoporosis, etc. The effect of nutraceuticals is similar to pharmaceuticals, even though the term nutraceutical has no regulatory definition. The usage of nutraceuticals, to prevent and treat the aforementioned diseases, is limited by several features such as poor water solubility, low bioavailability, low stability, low permeability, low efficacy, etc. These downsides can be overcome by the application of the field of nanotechnology manipulating the properties and structures of materials at the nanometer scale. In this review, the linear and cyclic dextrin, formed during the enzymatic degradation of starch, are highlighted as highly promising nanomaterials- based drug delivery systems. The modified cyclic dextrin, cyclodextrin (CD)-based nanosponges (NSs), are well-known delivery systems of several nutraceuticals such as quercetin, curcumin, resveratrol, thyme essential oil, melatonin, and appear as a more advanced drug delivery system than modified linear dextrin. CD-based NSs prolong and control the nutraceuticals release, and display higher biocompatibility, stability, and solubility of poorly water-soluble nutraceuticals than the CD-inclusion complexes, or uncomplexed nutraceuticals. In addition, the well-explored CD-based NSs pathways, as drug delivery systems, are described. Although important progress is made in drug delivery, all the findings will serve as a source for the use of CD-based nanosystems for nutraceutical delivery. To sum up, our review introduces the extensive literature about the nutraceutical concepts, synthesis, characterization, and applications of the CD-based nano delivery systems that will further contribute to the nutraceutical delivery with more potent nanosystems based on linear dextrins.

Keywords: cyclic dextrin; disease; drug delivery; linear dextrin; nano-carrier; nanosponges; nutraceutical delivery; nutraceuticals; starch.

Figure 1

Nutraceuticals.

Figure 2

Graph representing the number of research papers (found in PubMed) published on nutraceuticals per year.

Figure 3

Global Nutraceutical Market by Region (%) in 2015: U.S.A. (36%), Asia Pacific (30%), Europe (26%), and others include the rest of the world (8%) [83].

Figure 4

Classification of Nutraceuticals.

Figure 5

Formation of superoxide radical (•O₂−), hydrogen peroxide (H₂O₂), hydroxyl radical (•OH), and water by stepwise, univalent reductions of molecular oxygen.

Figure 6

The reaction of α-tocopherol during the autoxidation of unsaturated lipids. LOOH-lipid hydroperoxide; LO•-lipid-alkoxyl radical; L•carbon-centered lipid radical; LOO•-lipid-peroxyl radical; TO•-α tocopheroxyl radical; k-rate constant in M⁻¹ s⁻¹.

Figure 7

(a) The inhibition of the epithelial–mesenchymal transition (EMT) by phenolic compounds. The EMT is a critical part of cancer metastases and consists of the following key steps: Step 1 describes the subjecting of epithelial cancer cells to EMT which cells may then intravasate into the systemic circulation (Step 2). These EMT-induced cells must survive in the circulation (Step 3) before reaching the target. Then, the cells that reach Step 4 must extravasate into the tissue parenchyma upon reaching the target organ site and form micrometastases. At the end (Step 5), the mesenchymal–epithelial transition (MET) activation, another critical event for the metastasis of carcinomas, is required as a subsequent development into potentially life-threatening macrometastases [211,212]. (b) The prevention of free radical-induced damage to cellular DNA by carotenoids.

Figure 8

The essential requirements involved in biomaterial design for nutraceuticals delivery.

Figure 9

Chemical structure of starch with amylose, and amylopectin.

Figure 10

Methods of starch modification.

Figure 11

(a) Schematic representation of polymeric nanoparticles and (b) a model of the interaction between the aqueous phase containing a free hydrophilic drug or drug-loaded nanoparticle and the biological membrane model.

Figure 12

Schematic representation of the synthesis of cyclodextrin (CD)-based ester (PMDA), ether (EPI), carbonate (CDI), and urethane (TDI) nanosponges (NSs).

Figure 13

The cholesterol hydrogen succinate (CHS) grafting, in CD-based carbonate NSs (β-CD:DPC NSs), using coupling reaction.

Figure 14

Schematic representation of the synthesis of glutathione-responsive NSs, and molecularly imprinted CD-based carbonate NSs (L-DOPA used as a template).