Encapsulation,protection, and release of hydrophilic active components: Potential and limitations of colloidal delivery systems

There have been major advances in the development of edible colloidal delivery systems for hydrophobic bioactives in recent years. However, there are still many challenges associated with the development of effective delivery systems for hydrophilic bioactives. This review highlights the major challenges associated with developing colloidal delivery systems for hydrophilic bioactive components that can be utilized in foods, pharmaceuticals, and other products intended for oral ingestion. Special emphasis is given to the fundamental physicochemical phenomena associated with encapsulation, stabilization, and release of these bioactive components, such as solubility, partitioning, barriers, and mass transport processes. Delivery systems suitable for encapsulating hydrophilic bioactive components are then reviewed, including liposomes, multiple emulsions, solid fat particles, multiple emulsions, biopolymer particles, cubosomes, and biologically-derived systems. The advantages and limitations of each of these delivery systems are highlighted. This information should facilitate the rational selection of the most appropriate colloidal delivery systems for particular applications in the food and other industries.     

Structured emulsion-based delivery systems: Controlling the digestion and release of lipophilic food components

There is a need for edible delivery systems to encapsulate, protect and release bioactive and functional lipophilic constituents within the food and pharmaceutical industries. These delivery systems could be used for a number of purposes: controlling lipid bioavailability; targeting the delivery of bioactive components within the gastrointestinal tract; and designing food matrices that delay lipid digestion and induce satiety. Emulsion technology is particularly suited for the design and fabrication of delivery systems for lipids. In this article we provide an overview of a number of emulsion-based technologies that can be used as edible delivery systems by the food and other industries, including conventional emulsions, nanoemulsions, multilayer emulsions, solid lipid particles, and filled hydrogel particles. Each of these delivery systems can be produced from food-grade (GRAS) ingredients (e.g., lipids, proteins, polysaccharides, surfactants, and minerals) using relatively simple processing operations (e.g., mixing, homogenizing, and thermal processing). The structure, preparation, and utilization of each type of delivery system for controlling lipid digestion are discussed. This knowledge can be used to select the most appropriate emulsion-based delivery system for specific applications, such as encapsulation, controlled digestion, and targeted release.     

Recent Advances and Applications of Plant-Based Bioactive Saponins in Colloidal Multiphase Food Systems

The naturally occurring saponins exhibit remarkable interfacial activity and also possess many biological activities linking to human health benefits, which make them particularly attractive as bifunctional building blocks for formulation of colloidal multiphase food systems. This review focuses on two commonly used food-grade saponins, Quillaja saponins (QS) and glycyrrhizic acid (GA), with the aim of clarifying the relationship between the structural features of saponin molecules and their subsequent self-assembly and interfacial properties. The recent applications of these two saponins in various colloidal multiphase systems, including liquid emulsions, gel emulsions, aqueous foams and complex emulsion foams, are then discussed. A particular emphasis is on the unique use of GA and GA nanofibrils as sole stabilizers for fabricating various multiphase food systems with many advanced qualities including simplicity, ultrastability, stimulability, structural viscoelasticity and processability. These natural saponin and saponin-based colloids are expected to be used as sustainable, plant-based ingredients for designing future foods, cosmetics and pharmaceuticals.     

Zein as a source of functional colloidal nano- and microstructures

The application of colloidal particles from natural materials for purposes ranging from the delivery of bioactives to interfacial stabilisation and bulk structuring have recently gained a lot of interest for applications in the field of fast moving consumer goods, nutraceuticals, agricultural formulations and medicine. Zein-a proline rich water insoluble protein obtained from natural and sustainable source has been recently researched to generate colloidal structures that can find a wide range of applications. In this paper, we review the recent progress in the preparation of colloidal structures and their further application as functional materials in the field of delivery of functional ingredients and structuring of bulk phases and interfaces.     

Interaction between components of plant-based biopolymer systems

Proteins and polysaccharides are key elements in formulated foods, cosmetics, and pharmaceuticals. Their interaction behavior mainly determines the organoleptic, optical, textural, and rheological properties of foods. Traditionally, animal-based biopolymers have been widely used because of their excellent techno-functionality; however, plant-based alternatives gained enormous interest among scientists and manufacturers because of sustainable, religious, ethical, and nutritional reasons. The directed complexation of mixed biopolymers entirely originated from plants might be used to stabilize food colloids, modulate interfacial and bulk properties, control the release of bioactives, and mask bitter components. As such, this review highlights the general separation mechanism of mixed biopolymers systems entirely composed of plant-based biopolymers to be used as functional food ingredients. Particularly, ‘traditional’ and ‘novel’ proteins and polysaccharides obtained from different plant sources (e.g. soy, wheat, pea, potato, apple, citrus) are introduced to be assembled to modulate interfacial and bulk properties of food colloids.     

Sustainable Valorization of Tomato By-Products to Obtain Bioactive Compounds: Their Potential in Inflammation and Cancer Management

Tomato producing and processing industries present undoubted potential for industrial discarded products valorization whether due to the overproduction of fresh tomatoes or to the loss during processing. Although tomato by-products are not yet considered a raw material, several studies have suggested innovative and profitable applications. It is often referred to as “tomato pomace” and is quite rich in a variety of bioactive compounds. Lycopene, vitamin C, β-carotene, phenolic compounds, and tocopherol are some of the bioactives herein discussed. Tomato by-products are also rich in minerals. Many of these compounds are powerful antioxidants with anti-inflammatory properties besides modulating the immune system. Several researchers have focused on the possible application of natural ingredients, especially those extracted from foods, and their physiological and pharmacological effects. Herein, the effects of processing and further applications of the bioactive compounds present in tomato by-products were carefully reviewed, especially regarding the anti-inflammatory and anti-cancer effects. The aim of this review was thus to highlight the existing opportunities to create profitable and innovative applications for tomato by-products in health context.     

Polymeric Multilayer Capsules in Drug Delivery

Recent advances in medicine and biotechnology have prompted the need to develop nanoengineered delivery systems that can encapsulate a wide variety of novel therapeutics such as proteins, chemotherapeutics, and nucleic acids. Moreover, these delivery systems should be “intelligent”, such that they can deliver their payload at a well‐defined time, place, or after a specific stimulus. Polymeric multilayer capsules, made by layer‐by‐layer (LbL) coating of a sacrificial template followed by dissolution of the template, allow the design of microcapsules in aqueous conditions by using simple building blocks and assembly procedures, and provide a previously unmet control over the functionality of the microcapsules. Polymeric multilayer capsules have recently received increased interest from the life science community, and many interesting systems have appeared in the literature with biodegradable components and biospecific functionalities. In this Review we give an overview of the recent breakthroughs in their application for drug delivery.     

Delivery systems for liquid food products

One of the present challenges of the food industry is to deliver nutrition and health benefits to the consumer while keeping, or improving the taste and aroma impact. Adding active ingredients to liquid food products for fortification is in most cases not possible or not sufficient to achieve the desired goal, due to the fact that many interesting micronutrients are only hardly soluble in aqueous systems and show (i) a limited stability against chemical or physical degradation, (ii) an incompatibility between the active ingredient and the food matrix, or (iii) reveal an uncontrolled release or bioavailability. Therefore, encapsulation systems, also denoted as ‘delivery systems’, are typically used to solve these formulation problems. The task to find the appropriate delivery system is especially challenging for the food industry compared to other fields such as pharmacy, medical products or cosmetics, since only a limited amount of ingredients can be used as encapsulation and stabilization material. In the present review we will discuss the delivery systems available for (semi)-liquid foods and comment on existing advantages and limitations. The remaining technical challenges to solve in the future concern mainly the facts that (i) most of the available delivery systems for aqueous products do not yet allow to significantly stabilize degradation sensitive ‘encapsulated’ active ingredients against e.g. oxidation, (ii) the ‘encapsulation’ (solubilization) capacity of some delivery systems is still quite poor and (iii) off-taste generation is possible above certain concentrations of added delivery systems.     

Plant-Based Gums and Mucilages Applications in Pharmacology and Nanomedicine: A Review

Gums are carbohydrate biomolecules that have the potential to bind water and form gels. Gums are regularly linked with proteins and minerals in their construction. Gums have several forms, such as mucilage gums, seed gums, exudate gums, etc. Plant gums are one of the most important gums because of their bioavailability. Plant-derived gums have been used by humans since ancient times for numerous applications. The main features that make them appropriate for use in different applications are high stabilization, viscosity, adhesive property, emulsification action, and surface-active activity. In many pharmaceutical formulations, plant-based gums and mucilages are the key ingredients due to their bioavailability, widespread accessibility, non-toxicity, and reasonable prices. These compete with many polymeric materials for use as different pharmaceuticals in today’s time and have created a significant achievement from being an excipient to innovative drug carriers. In particular, scientists and pharmacy industries around the world have been drawn to uncover the secret potential of plant-based gums and mucilages through a deeper understanding of their physicochemical characteristics and the development of safety profile information. This innovative unique class of drug products, useful in advanced drug delivery applications, gene therapy, and biosynthesis, has been developed by modification of plant-based gums and mucilages. In this review, both fundamental and novel medicinal aspects of plant-based gums and mucilages, along with their capacity for pharmacology and nanomedicine, were demonstrated.     

Plant Protein-Based Delivery Systems: An Emerging Approach for Increasing the Efficacy of Lipophilic Bioactive Compounds

The development of plant protein-based delivery systems to protect and control lipophilic bioactive compound delivery (such as vitamins, polyphenols, carotenoids, polyunsaturated fatty acids) has increased interest in food, nutraceutical, and pharmaceutical fields. The quite significant ascension of plant proteins from legumes, oil/edible seeds, nuts, tuber, and cereals is motivated by their eco-friendly, sustainable, and healthy profile compared with other sources. However, many challenges need to be overcome before their widespread use as raw material for carriers. Thus, modification approaches have been used to improve their techno-functionality and address their limitations, aiming to produce a new generation of plant-based carriers (hydrogels, emulsions, self-assembled structures, films). This paper addresses the advantages and challenges of using plant proteins and the effects of modification methods on their nutritional quality, bioactivity, and techno-functionalities. Furthermore, we review the recent progress in designing plant protein-based delivery systems, their main applications as carriers for lipophilic bioactive compounds, and the contribution of protein-bioactive compound interactions to the dynamics and structure of delivery systems. Expressive advances have been made in the plant protein area; however, new extraction/purification technologies and protein sources need to be found Their functional properties must also be deeply studied for the rational development of effective delivery platforms.     

Current knowledge on the interfacial behaviour limits our understanding of plant protein functionality in emulsions

For different reasons, there is an increasing interest in plant-based foods as well as vegetarian and vegan dairy and meat alternatives. Frequently, those foods represent dispersed systems and more specifically food emulsions with proteins as emulsifying food ingredients. Owing to a very heterogeneous composition of plant proteins and a wide range of structural varieties in the proteins, it is worth discussing if our current understanding of interfacial and emulsifying properties of proteins is sufficient to meet the challenges associated with the utilisation of plant proteins for the stabilisation of food emulsions. To this purpose, we review the current understanding of the interfacial behaviour of proteins, summarise analytical techniques for their characterisation and critically discuss the available literature on oilseed and legume proteins to identify future research needs and opportunities for customised emulsion design.     

Self-emulsification in chemical and pharmaceutical technologies

The interest in the low energy self-emulsification techniques has exploded in the recent years, driven by three main trends: by the transition to “greener” technologies in both its aspects—less energy consumption and replacement of the petrochemicals by natural ingredients; by the costly and maintenance demanding equipment for nanoemulsification; and by the quest for efficient and robust self-emulsifying formulations for oral drug delivery. Here, we first present a brief overview of the main known low-energy methods for nanoemulsion formation, focusing on their mechanistic understanding and discussing some recent advances in their development and applications. Next, we review three conceptually new approaches for self-emulsification in chemical technologies, discovered in the last several years. The colloidal features and the specific requirements of the self-emulsifying drug-delivery systems (SEDDS) are also discussed briefly. Finally, we summarize the current trends and the main challenges in this vivid research area.     

Amphiphilic micro- and nanogels: Combining properties from internal hydrogel networks,solid particles,and micellar aggregates

Polymeric micro- and nanogels are defined by their water-swollen hydrophilic networks that can often impart outstanding biocompatibility and high-colloidal stability. Unfortunately, this highly hydrophilic nature limits their potential in areas where hydrophobic or amphiphilic interactions are required, for example, the delivery of hydrophobic cargoes or tailored interactions with amphipathic (bio-)surfaces. To overcome this limitation, amphiphilic micro−/nanogels are emerging as new colloidal materials that combine properties from hydrogel networks with hydrophobic segments, known from solid hydrophobic polymer particles or micellar cores. The ability to accurately adjust the balance of hydrophobic and hydrophilic components in such amphiphilic colloidal systems enables new tailored properties. This opens up new applications ranging from the controlled and sustained delivery of hydrophobic drugs, over carriers for catalytic moieties, to their assembly at hydrophilic/hydrophobic interfaces, for example, as advanced stabilizers in Pickering emulsions. While promising, the synthetic realization of such amphiphilic materials remains challenging since hydrophobic and hydrophilic moieties need to be combined in a single colloidal system. As a result, adjusting the micro−/nanogel amphiphilicity often changes the colloidal features too. To overcome these limitations, various strategies have been reported. The aim of this review is to give a brief overview of important synthetic tools, considering both advantages and disadvantages, thus critically evaluating their potential in different research fields.     

Understanding the interfacial properties of nanostructured liquid crystalline materials for surface-specific delivery applications

Nonlamellar liquid crystalline dispersions such as cubosomes and hexosomes have great potential as novel surface-targeted active delivery systems. In this study, the influence of internal nanostructure, chemical composition, and the presence of Pluronic F127 as a stabilizer, on the surface and interfacial properties of different liquid crystalline particles and surfaces, was investigated. The interfacial properties of the bulk liquid crystalline systems with coexisting excess water were dependent on the internal liquid crystalline nanostructure. In particular, the surfaces of the inverse cubic systems were more hydrophilic than that of the inverse hexagonal phase. The interaction between F127 and the bulk liquid crystalline systems depended on the internal liquid crystalline structure and chemical composition. For example, F127 adsorbed to the surface of the bulk phytantriol cubic phase, while for monoolein cubic phase, F127 was integrated into the liquid crystalline structure. Last, the interfacial adsorption behavior of the dispersed liquid crystalline particles also depended on both the internal nanostructure and the chemical composition, despite the dispersions all being stabilized using F127. The findings highlight the need to understand the specific surface characteristics and the nature of the interaction with colloidal stabilizer for understanding and optimizing the behavior of nonlamellar liquid crystalline systems in surface delivery applications.     

Protein–polysaccharide associative interactions in the design of tailor-made colloidal particles

This article reviews some recent advances in the use of diverse protein–polysaccharide associative interactions in the design of colloidal particles having potential to be used for both fortification of food colloids with health-promoting bioactive compounds with better control of their physical stability and breakdown within the gastrointestinal tract. Protein–polysaccharide associative interactions are discussed in the following aspects: (i) the formation of micro- and nanoparticles for the delivery of health promoting ingredients (nutraceuticals); (ii) the controlled gastrointestinal fate of colloidal particles; (iii) the formation of biopolymer-based particles as fat replacers; and (iv) the behavior of colloidal particles as stabilizers of emulsions and foams. The first aspect concerns soluble protein–polysaccharide complex particles (electrostatic nanocomplexes, complex coacervates, covalent conjugates), mixed hydrogel particles, and nanoemulsion-based delivery systems.     

Tailoring nanocarriers for intracellular protein delivery

Proteins play a crucial role in life, taking part in all vital processes in the body. In the past decade, there was increasing interest in delivering active forms of proteins to specific cells and organs. Intracellular protein delivery holds enormous promise for biological and medical applications, including cancer therapy, vaccination, regenerative medicine, treatment for loss-of-function genetic diseases and imaging. This tutorial review surveys recent developments in intracellular protein delivery using various nanocarriers. Methods such as lipid-mediated colloidal systems, polymeric nanocarriers, inorganic systems and protein-mediated carriers are reviewed. Advantages and limitations of current strategies, as well as future opportunities and challenges are also discussed.     

Nanodiamonds: A Cutting-Edge Approach to Enhancing Biomedical Therapies and Diagnostics in Biosensing

Nanodiamonds (NDs) have garnered attention in the field of nanomedicine due to their unique properties. This review offers a comprehensive overview of NDs synthesis methods, properties, and their uses in biomedical applications. Various synthesis techniques, such as detonation, high-pressure, high-temperature, and chemical vapor deposition, offer distinct advantages in tailoring NDs′ size, shape, and surface properties. Surface modification methods further enhance NDs′ biocompatibility and enable the attachment of bioactive molecules, expanding their applicability in biological systems. NDs serve as promising nanocarriers for drug delivery, showcasing biocompatibility and the ability to encapsulate therapeutic agents for targeted delivery. Additionally, NDs demonstrate potential in cancer treatment through hyperthermic therapy and vaccine enhancement for improved immune responses. Functionalization of NDs facilitates their utilization in biosensors for sensitive biomolecule detection, aiding in precise diagnostics and rapid detection of infectious diseases. This review underscores the multifaceted role of NDs in advancing biomedical applications. By synthesizing NDs through various methods and modifying their surfaces, researchers can tailor their properties for specific biomedical needs. The ability of NDs to serve as efficient drug delivery vehicles holds promise for targeted therapy, while their applications in hyperthermic therapy and vaccine enhancement offer innovative approaches to cancer treatment and immunization. Furthermore, the integration of NDs into biosensors enhances diagnostic capabilities, enabling rapid and sensitive detection of biomolecules and infectious diseases. Overall, the diverse functionalities of NDs underscore their potential as valuable tools in nanomedicine, paving the way for advancements in healthcare and biotechnology.     

A Review of Potential Use of Amazonian Oils in the Synthesis of Organogels for Cosmetic Application

New strategies for the delivery of bioactives in the deeper layers of the skin have been studied in recent years, using mainly natural ingredients. Among the strategies are organogels as a promising tool to load bioactives with different physicochemical characteristics, using vegetable oils. Studies have shown satisfactory skin permeation, good physicochemical stability mainly due to its three-dimensional structure, and controlled release using vegetable oils and low-molecular-weight organogelators. Within the universe of natural ingredients, vegetable oils, especially those from the Amazon, have a series of benefits and characteristics that make them unique compared to conventional oils. Several studies have shown that the use of Amazonian oils brings a series of benefits to the skin, among which are an emollient, moisturizing, and nourishing effect. This work shows a compilation of the main Amazonian oils and their nutraceutical and physicochemical characteristics together with the minority polar components, related to health benefits, and their possible effects on the synthesis of organogels for cosmetic purposes.     

Hybrid niosome complexation in the presence of oppositely charged polyions

We have investigated the formation of complexes between negatively charged niosomal vesicles (hybrid niosomes), built up by dicethylphosphate [DCP], Tween 20 and Cholesterol, and three linear differently charged cationic polyions, such as alpha-polylysine, epsilon-polylysine, and polyethylvinylpyridinium bromide [PEVP], with two different substitution degrees. Our aim is to investigate the interaction mechanism between anionic-nonionic vesicles (hybrid niosomes) and linear polycations, characterizing the resulting aggregates in view of possible applications of these composite colloidal particles as vectors for multidrug delivery. In order to explore the aggregation behavior of the complexes and to gain information on the stability of the single niosomal vesicles within the aggregates, we employed dynamic light scattering (DLS), laser Doppler electrophoretic measurements, and fluorescence measurement techniques. The overall phenomenology is well described in terms of the re-entrant condensation and charge inversion behavior, observed in different colloidal systems. The aggregate size and overall charge depend on the charge ratio between vesicles and polyions, and the aggregates reach their maximum size at the point of charge inversion (re-entrant condensation). While the overall phenomenology is similar for all three polycations investigated, the stability and the integrity of the hybrid niosomal vesicles forming the aggregates strongly depend on the chemical structure of the polycations. The role of the polycations in the aggregation process is discussed by identifying specific interactions with the niosomal membrane, pointing out their importance for possible applications as drug delivery vectors.     

Protein nanocage-stabilized Pickering emulsions

The utilization of surface-active engineered protein nanocages as stabilizers for emulsions provides avenues for the design of new tailor-made functional materials in various fields including food, pharmaceutical, and biotechnology. They can be used to codeliver bioactive molecules of different polarities in a tailored manner to the body, act as a platform for screening cells or enzymes, or function as targeted drug delivery systems. Knowledge on the mechanisms that underlie the protein nanocage-driven stabilization of emulsions and their colloidal structure can have direct implications for the rational design of the new advanced functional colloids.This contribution summarizes the recent progress in protein nanocage-stabilized emulsions. It discusses the advances in the precision bioengineering of protein nanocages for emulsion design, highlights challenges in the characterization of structure and dynamics in these materials, and demonstrates selected applications in the field of functional food materials.