The intelligent delivery systems for bioactive compounds in foods: Physicochemical and physiological conditions,absorption mechanisms,obstacles and responsive strategies

BackgroundBioactive natural compounds have received considerable attention due to their health benefits, including anti-oxidant, anti-cancer, anti-diabetes and cardiovascular disease-preventing functions. However, the stability of these sensitive compounds can be influenced by unfavourable environmental conditions during processing and storage. In addition, delivery of bioactive compounds via the oral route is restricted by various physiological barriers, including a harsh pH, gastrointestinal enzymes, the mucus layer, and the epithelium. Intelligent delivery systems are a promising method to protect bioactive molecules from degradation and improve their bioavailability.Scope and approachWe have demonstrated the physicochemical and physiological GI conditions. The structural composition of the epithelium and transport mechanisms of bioactives and nanoparticles across the intestinal epithelium were discussed. The effects of enhanced aqueous solubility, stability, bioaccessibility and bioavailability after encapsulation were illustrated. Furthermore, novel intelligent carriers that are responsive to the oral route, pH, enzymes and cell receptors were also discussed.Key findings and conclusionsThis comprehensive multidisciplinary review provides useful guidelines for the application of bioactive compounds in the food industry. Intelligent carrier systems are designed to improve the low solubility, poor stability and low permeability of the gastrointestinal tract, and they have the potential to improve oral bioavailability.     

槲皮素及其递送体系的研究进展

槲皮素是一种广泛存在于食品中的生物活性物质，具有抗氧化、抗炎症、抗肿瘤、预防心血管疾病等功效。为解决其水溶性差、稳定性低等问题，前人已围绕着槲皮素的递送体系展开了大量研究。为此，本文结合国内外研究进展，从槲皮素的理化特性、生物活性、稳定性、体内代谢及其递送体系的角度进行了综述。并在此基础上对槲皮素及其递送体系的安全性进行了介绍，旨在为拓展其在食品领域的应用提供相关理论依据。     

花色苷递送系统研究进展

花色苷作为植物中常见的功能色素物质,具有广泛的生理功能。然而,花色苷在加工和贮存过程中稳定性较差,容易发生降解。许多研究报道递送系统可应用于提高花色苷稳定性,进而提高其在体内的生物利用度。本文介绍了花色苷在人体内消化吸收的过程,并综述了目前用于提高花色苷肠道稳定性的几种递送系统,包括蛋白质递送系统、多糖递送系统、脂质体递送系统、复乳体系递送系统以及复合递送系统,以期为功能因子在食物中的进一步开发和利用提供理论依据。     

Encapsulation systems for lutein: A review

BackgroundThe increased demand by consumers for clean labels has encouraged industry to search for replacements of synthetic ingredients in food products, and in particular, colorants. Lutein, a xanthophyll found in marigolds and corn, can be used in food products as a natural colorant replacing yellow food dyes. Moreover, lutein is considered a nutraceutical due to its potentially beneficial health effects, such as prevention of macular degeneration, role in the development of the visual and nervous systems of fetuses, and its antioxidant properties. However, incorporation of lutein into foods is often limited because of its low-water solubility, chemical instability, and poor oral bioavailability. For this reason, colloidal encapsulation systems have been developed to facilitate the incorporation of lutein into aqueous food and beverage products.Scope and approachThis review focuses on exploring encapsulation options for lutein using various emulsion-based, nanoparticle- and microparticle-based and molecular inclusion encapsulation systems, as well as additives that can be used to increase its chemical stability in these systems. This review covers all aspects of lutein encapsulation, including both food-grade and pharmaceutical-grade encapsulation systems.Key findings and conclusionsThough lutein-loaded encapsulation systems are extensively explored in this review, emulsions are of the most interest in industry as they are cost efficient and can be designed to increase the stability of lutein by selecting the proper emulsifiers and emulsification techniques. Despite the extensive amount of research carried out on the encapsulation of hydrophobic bioactive molecules such as lutein, there are still opportunities to develop encapsulation systems that further protect these molecules during storage and also increase their bioavailability after ingestion.     

Advances in smart delivery of food bioactive compounds using stimuli-responsive carriers: Responsive mechanism,contemporary challenges,and prospects

Many important food bioactive compounds are plant secondary metabolites that have traditional applications for health promotion and disease prevention. However, the chemical instability and poor bioavailability of these compounds represent major challenges to researchers. In the last decade, therefore, major impetus has been given for the research and development of advanced carrier systems for the delivery of natural bioactive molecules. Among them, stimuli-responsive carriers hold great promise for simultaneously improving stability, bioavailability, and more importantly delivery and on-demand release of intact bioactive phytochemicals to target sites in response to certain stimuli or combination of them (e.g., pH, temperature, oxidant, enzyme, and irradiation) that would eventually enhance therapeutic outcomes and reduce side effects. Hybrid formulations (e.g., inorganic–organic complexes) and multi-stimuli-responsive formulations have demonstrated great potential for future studies. Therefore, this review systematically compiles and assesses the recent advances on the smart delivery of food bioactive compounds, particularly quercetin, curcumin, and resveratrol through stimuli-responsive carriers, and critically reviews their functionality, underlying triggered-release mechanism, and therapeutic potential. Finally, major limitations, contemporary challenges, and possible solutions/future research directions are highlighted. Much more research is needed to optimize the processing parameters of existing formulations and to develop novel ones for lead food bioactive compounds to facilitate their food and nutraceutical applications.     

界面工程设计调控油脂基乳液递送体系中脂溶性营养素生物利用率的研究进展

膳食补充已日渐成为维持人类身体健康的重要干预手段。随着高通量筛选技术的发展，越来越多的营养素被挖掘出来。但很多营养素为脂溶性营养素，其水溶性低、稳定性差、生物利用率低。为此，脂溶性营养素递送体系的设计与开发受到了广泛关注。其中乳液递送体系独具特色，且已被证实能有效改善营养素生物利用率。依据乳液中两相界面的特点，本文综述了油脂基乳液递送体系的界面工程（包括简单界面、复杂界面）对所含脂溶性营养素生物利用率的调控，为改善脂溶性营养素生物效价提供参考。     

Nano- and micro-particles for delivery of catechins: Physical and biological performance

Catechins, present in many fruits and vegetables, have many health benefits, but they are prone to degradation. Nano- and micro-particle systems have been used to stabilise catechins when exposed to adverse environments and to improve their bioavailability after ingestion. This review discusses the inherent properties of various catechins, the design of delivery formulations and the properties of catechin-loaded nano- and micro-particles. The protection afforded to catechins during exposure to harsh environmental conditions and gastrointestinal tract transit is reviewed. The bioavailability and efficacy of encapsulated catechins, as assessed by various in vitro and in vivo conditions, are discussed. Bioavailability based on uptake in the upper gut alone underestimates the bioavailability as polyphenols. The caveats with interpretation of bioavailability based on various tests are discussed, when taking into consideration the pathways of catechin metabolism including the role of the gut microflora. However, taken together, the weight of the evidence suggests that there are potentially improved health benefits with the use of appropriately designed nano- and micro-particles for delivery of catechins. Further systematic studies on the metabolism and physiological effects of encapsulated catechins in vivo and clinical trials are needed to validate the bioefficacy of the encapsulated catechins.     

Recent advances in emulsion-based delivery approaches for curcumin: From encapsulation to bioaccessibility

BackgroundCurcumin has been widely acknowledged for its health-promoting effects. However, its application is often limited by its poor water solubility and biochemical/structural degradation during physiological transit that restricts its bioavailability. Emulsion based approaches have attracted the most research attention to encapsulate curcumin and improve its stability, bioaccessibility and bioavailability.Scope and approachThis review summarizes the recent advances in application of different oil-in-water emulsion-based approaches, such as, conventional emulsions (surfactants-, protein- and protein-polysaccharide-stabilized emulsions), nanoemulsions, and Pickering emulsions that have been specifically used to deliver curcumin. Particular emphasis is given to factors affecting curcumin solubility, change in crystalline structure of curcumin upon dispersion and encapsulation efficiency. Changes in the droplet size and emulsion stability during in vitro oral-to-gastrointestinal digestion are discussed, with clear focus on the bioaccessibility of the encapsulated curcumin.Key findings and conclusionsKey factors that influence curcumin delivery include emulsion droplet size, oil composition, volume fraction, dispersion conditions of curcumin in the oil phase and the type of interfacial materials. Nanoemulsions have been the preferred choice for delivery of curcumin up to now. Although scarce in literature, emulsions stabilized by edible Pickering particles as shown by recent evidence are effective in protecting curcumin in an in vitro gastrointestinal setting due to their high coalescence stability. Further studies with emulsions stabilized by food-grade particles and accurate tracking of the physiological fate (in vitro to human trials) of different emulsion-based delivery vehicles are essential for rational designing of curcumin-rich functional foods with high bioaccessibility.     

Designing emulsion droplets of foods and beverages to enhance delivery of lipophilic bioactive components – a review of recent advances

Lipophilic bioactive compounds such as lipids, vitamins and phytochemicals serve important antioxidant, functional, nutritional and structural roles in the human body. Colloidal systems such as emulsions are particularly suitable matrices for the protection and delivery of these compounds. This article summarises the principal lipophilic bioactives important for human health and challenges associated with their delivery. It discusses the compositional and physical characteristics of emulsions in relation to bioactive delivery, and chemical stability aspects to consider when engineering efficient emulsion delivery systems. The literature shows that aspects such as oil type, droplet size, interfacial composition and solubilisation capacity impact bioactive availability and that their effects are bioactive specific. Therefore, emulsions must be tailored to the bioactives delivered. Much of the present knowledge is based on in vitro studies, and more data from animal and human models are required to better understand the relationship between emulsion characteristics and bioavailability of lipophilic bioactives.     

Biopolymer nanoparticles: a strategy to enhance stability,bioavailability, and biological effects of phenolic compounds as functional ingredients

Phenolic compounds are abundant in nature and have multiple beneficial effects on human health due to their antioxidant, anti-inflammatory, antithrombotic, antiallergenic, anticancer, and antiatherosclerotic properties. For this reason, phenolics are becoming relevant functional ingredients for several industries, mainly the food industry, derived from food consumer exigencies and regulations. However, the use of their beneficial properties still presents some limitations, such as chemical instability under environmental and processing conditions, which leads to structural changes and compromises their biological activities. They also present poor water solubility and sensitivity to pH changes, decreasing their bioavailability in the organism. The technologies for extraction and stabilization of these compounds have evolved rapidly in the development of different delivery systems to encapsulate sensitive active molecules. Biopolymeric nanoparticles are biodegradable polymer-based colloidal systems with sizes ranging from 1 to 1000 nm, and different techniques can be carried out to develop them. These systems have emerged as a green and effective alternative to improve stability, bioavailability, and biological effects of phenolic compounds. This comprehensive review aims to present an overview of recent advances in encapsulation processes of phenolic compounds within biopolymer nanoparticles as delivery systems and the impact on their physicochemical properties and biological effects after encapsulation. © 2021 Society of Chemical Industry.     

Quercetin in Food: Possible Mechanisms of Its Effect on Memory

Quercetin (3,3′,4′,5,7‐pentahydroxyflavone) is found in vegetables and fruits. It is one of the major flavonoids that is part of human diets. Quercetin has several pharmacological effects in the nervous system as a neuroprotective agent. In this review, we summarize the research on quercetin and its role in memory in both animals and humans. Articles were chosen from the Scopus, PubMed, and Web of Science databases. In this review, we describe and summarize the importance of quercetin's presence in the body, particularly in the brain; its kinetics, including its absorption, metabolism, distribution, and excretion; its behavioral effects; and some of the possible mechanisms of action of quercetin on memory in different animal models. Several important pathways that may be involved in the processes of learning and memory, long‐term potentiation, and cognition may be impaired during neurological diseases or other medical conditions. As dietary quercetin is important, provision of its best formulation for delivery to the brain as a nutraceutical and in clinical translational research for the prevention or treatment of Alzheimer's disease and other types of dementia is necessary.     

Bioavailability of the flavonol quercetin in cows after intraruminal application of quercetin aglycone and rutin

The bioavailability of quercetin has been intensively investigated in monogastric species, but knowledge about its bioavailability in ruminants does not exist. Thus, the aim of the present study was to determine the bioavailability of quercetin in nonlactating cows equipped with indwelling catheters placed in one jugular vein after intraruminal and additionally after i.v. application, respectively. Quercetin was administered intraruminally in equimolar amounts, either in the aglycone form or as its glucorhamnoside rutin, each at 2 dosages [10 and 50mg of quercetin/kg of body weight (BW)]. In a second trial, 0.8mg of quercetin aglycone/kg of BW was applied i.v. Blood samples were drawn 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, and 24h after intraruminal application and every 5min (first hour), every 10min(second hour), and at 3 and 6h after i.v. bolus application, respectively. Quercetin and quercetin metabolites with an intact flavonol structure (isorhamnetin, tamarixetin, and kaempferol) in plasma samples were analyzed by HPLC with fluorescence detection. After intraruminal application of quercetin and rutin, respectively, quercetin and its methylated (isorhamnetin, tamarixetin) and dehydroxylated (kaempferol) derivatives were present in plasma mainly as conjugated forms, whereas free quercetin and its derivatives were scarcely detected. For rutin, the relative bioavailability of total flavonols (sum of conjugated and nonconjugated quercetin and its conjugated and nonconjugated derivatives after intake of 50mg/kg of BW) was 767.3% compared with quercetin aglycone (100%). Absolute bioavailability of total flavonols was only 0.1 and 0.5% after quercetin aglycone and rutin applications, respectively. Our data demonstrate that bioavailability of quercetin from rutin is substantially higher compared with that from quercetin aglycone in cows after intraruminal (or oral) application, unlike in monogastric species.     

Beta-carotene: Digestion, Microencapsulation, and In Vitro Bioavailability

Beta-carotene is an important nutrient for human health, but its low absorption from natural sources has led to the development of microencapsulation methods to improve stability and bioavailability. To properly design a gastrointestinal delivery system for beta-carotene, the processes occurring during digestion from mastication to absorption must first be understood. This review provides an overview of beta-carotene digestion and microencapsulation methods, with an emphasis placed on spray-drying and gelation. Given the lack of a standardized in vitro model to study the bioavailability of beta-carotene, important parameters that have been shown to affect bioavailability of beta-carotene (i.e., pH, enzyme concentration, type of model) are discussed to ensure measurements are made using physiologically relevant conditions. Current quantitative methods to measure beta-carotene after digestion are evaluated to ensure accuracy and precision of measurements. This study contributes to the knowledge concerning beta-carotene digestion, release, and absorption and provides guidelines for developing microencapsulation methods and in vitro digestion protocols to accurately measure in vitro bioavailability.     

Effect of Processed Onions on the Plasma Concentration of Quercetin in Rats and Humans

Onion is a major dietary source of the bioactive flavonoid, quercetin. Quercetin aglycone (QA) is exclusively distributed in the onion peel, although quercetin‐4′‐β‐O‐glucoside (Q4′G) is present in both the peel and the bulb, and quercetin‐3,4′‐β‐O‐diglucoside (Q3,4′diG) is present only the bulb. The bioavailability of flavonoids from fruits and vegetables is frequently affected by the manufacturing process and related conditions. The present study aimed to estimate the effect of food processing on the bioavailability of onion QA and its glucosides, Q4′G and Q3,4′diG, provided through the consumption of onion products. Rats were fed onion peel and onion bulb products‐mixed meal or pure QA/Q4′G+Q3,4′diG‐mixed meal at 5 mg QA equivalent/kg body weight. A comparison of the blood plasma concentrations strongly suggested that quercetin glucosides (Q4′G and Q3,4′diG) are superior or at least equal to QA in their bioavailability, when each purified compound is mixed with the meal. The intake of a peel powder‐containing meal provided a significantly higher increase of plasma quercetin concentration than the peel extract, bulb powder, bulb extract, and bulb sauté containing meals at each period tested. A human ingestion study confirmed the superiority of onion peel powder to onion peel extract. The difference of log P for QA between peel powder and peel extract indicated that a food matrix improves the bioavailability of QA in onion peel products. These results demonstrated that the bioavailability of quercetin provided by not the onion bulb but the onion peel is significantly affected by food processing.     

Emulsion electrospinning: Fundamentals,food applications and prospects

BackgroundIn the past decades, many natural bioactive compounds with antioxidant, immunoregulatory, antimicrobial, and anticancer activities have been successfully identified in plant and animal materials. However, due to their poor solubility, unfavorable flavor, low bioavailability and instability during food processing and storage, the development of bioactive compounds used in the food industry presents many technological challenges.Scope and approachEmulsion electrospinning is a novel and simple technique to fabricate core-shell nanofibers, and either water-in-oil (W/O) or oil-in-water (O/W) emulsions can be electrospun to directly encapsulate hydrophilic or hydrophobic compounds into core-shell fibers, respectively. This review introduces fundamentals and advantages of emulsion electrospinning as well as its food applications. The effects of different types of emulsifiers on the formation of emulsion systems and emulsion-based electrospun fibers are highlighted. Further, the existing limitations and scope for future research are discussed.Key findings and conclusionsRecent studies have found that the emulsion-based electrospun nanofibers can enhance the encapsulation efficiency, stability, and bioavailability of bioactive compounds, as well as achieve targeted delivery and controlled release, thus providing new strategies to improve their barrier performance compared to conventional electrospinning and therefore facilitating the development of emulsion-based electrospun mats in the food industry.     

Quercetin content in some food and herbal samples

Quercetin is a typical flavonoid ubiquitously present in vegetables and fruits, and its antioxidant effect is implied to be helpful for human health. The efficiency of extraction process and acidic hydrolysis parameters for HPLC analysis of quercetin present in glycosides and aglycone forms was investigated. Hydrolysis for 5 min in the presence of 2.8 M HCl as well as for 10 min with 1.1 M HCl efficiently released quercetin from rutin. The method developed in this study was applied for quantitative determination of quercetin in some food (onion, apple) and herbal (Hypericum perforatum and Sambucus nigra) products.     

Improving the bioavailability of phenolic compounds by loading them within lipid-based nanocarriers

BackgroundPhenolic compounds¹ are one of the main interested nutraceuticals in the food and pharmaceutical industries. The application of phenolics is limited due to their low bioavailability, low solubility, low stability, and un-targeted release. These limitations could be overcome by novel ‘‘lipid-based nano-encapsulation technologies’’ capable of appropriated and targeted delivery functions into foods.Scope and approachIn this review, preparation, application, and characterization of lipid-based nanocarriers for phenolics have been considered and discussed including nano-emulsions, nano-scale phospholipids, and nanostructured lipid carriers. The bioavailability of nano-encapsulated phenolic products and capability of them to produce functional foods have been considered as well.Key findings and conclusionsIn the food and nutraceutical industries, the main aims of loading phenolics into nanocarriers are masking their undesirable flavor for oral administration, providing high stability and high absorption, and better release in gastrointestinal (GIT) conditions. Compared with micro-sized carriers, nanocapsules based on lipid formulations provide more surface area and have the potential to enhance solubility, improve bioavailability, and ameliorate controlled release of the nano-encapsulated phenolic compounds.     

Food content, processing, absorption and metabolism of onion flavonoids

The question as to how far the development of chronic diseases in humans depends on diet still remains open. Simultaneously, epidemiological studies suggest the consumption of a flavonoids rich diet might decrease the risk of degenerative changes and certain diseases. The intake of this group of compounds as to quality and quantity depends on dietary habits and a widespread presence of quercetin in the diet makes this compound one of the key factors. Onion, one of the richest and most common quercetin sources, was particularly often studied in different aspects. Quercetin is present in onion mainly as glycosides, of which the distribution within the onion bulb changes in onion processing, and biological activities attracted a lot of attention. Especially antioxidative activity demonstrated in vitro was initially associated with most of the beneficial effects of quercetin on the human body. However, after ingestion quercetin undergoes extensive metabolism and microbial action resulting in its altered or degraded structure; therefore, most of the effects shown in in vitro experiments with the pure compound cannot be directly extrapolated to in vivo systems. Yet, this does not mean that quercetin simultaneously loses its positive impact on consumer health. Even after being metabolized it may still affect the redox balance by inducing antioxidative and detoxifying enzymes or compounds which may be involved in sustaining homeostasis.     

Modifying wheat bran to improve its health benefits

Abstract

Consumption of wheat bran (WB) has been associated with improved gastrointestinal health and a reduced risk for colorectal cancer, cardiovascular diseases and metabolic disorders. These benefits are likely mediated by a combination of mechanisms, including colonic fermentation of the WB fiber, fecal bulking and the prevention of oxidative damage due to its antioxidant capacities. The relative importance of those mechanisms is not known and may differ for each health effect. WB has been modified by reducing particle size, heat treatment or modifying tissue composition to improve its technological properties and facilitate bread making processes. However, the impact of those modifications on human health has not been fully elucidated. Some modifications reinforce whereas others attenuate the health effects of coarse WB. This review summarizes available WB modifications, the mechanisms by which WB induces health benefits, the impact of WB modifications thereon and the available evidence for these effects from in vitro and in vivo studies.