Recent Advances in Encapsulation, Protection, and Oral Delivery of Bioactive Proteins and Peptides using Colloidal Systems

There are many areas in medicine and industry where it would be advantageous to orally deliver bioactive proteins and peptides (BPPs), including ACE inhibitors, antimicrobials, antioxidants, hormones, enzymes, and vaccines. A major challenge in this area is that many BPPs degrade during storage of the product or during passage through the human gut, thereby losing their activity. Moreover, many BPPs have undesirable taste profiles (such as bitterness or astringency), which makes them unpleasant to consume. These challenges can often be overcome by encapsulating them within colloidal particles that protect them from any adverse conditions in their environment, but then release them at the desired site-of-action, which may be inside the gut or body. This article begins with a discussion of BPP characteristics and the hurdles involved in their delivery. It then highlights the characteristics of colloidal particles that can be manipulated to create effective BPP-delivery systems, including particle composition, size, and interfacial properties. The factors impacting the functional performance of colloidal delivery systems are then highlighted, including their loading capacity, encapsulation efficiency, protective properties, retention/release properties, and stability. Different kinds of colloidal delivery systems suitable for encapsulation of BPPs are then reviewed, such as microemulsions, emulsions, solid lipid particles, liposomes, and microgels. Finally, some examples of the use of colloidal delivery systems for delivery of specific BPPs are given, including hormones, enzymes, vaccines, antimicrobials, and ACE inhibitors. An emphasis is on the development of food-grade colloidal delivery systems, which could be used in functional or medical food applications. The knowledge presented should facilitate the design of more effective vehicles for the oral delivery of bioactive proteins and peptides

Development of Next-Generation Nutritionally Fortified Plant-Based Milk Substitutes: Structural Design Principles

Consumers are increasingly interested in decreasing their dietary intake of animal-based food products, due to health, sustainability, and ethical concerns. For this reason, the food industry is creating new products from plant-based ingredients that simulate many of the physicochemical and sensory attributes associated with animal-derived foods, including milk, eggs, and meat. An understanding of how the ingredient type, amount, and organization influence the desirable physicochemical, sensory, and nutritional attributes of these plant-based foods is required to achieve this goal. A potential problem with plant-based diets is that they lack key micronutrients, such as vitamin B12, vitamin D, calcium, and ω-3 fatty acids. The aim of this review is to present the science behind the creation of next-generation nutritionally fortified plant-based milk substitutes. These milk-like products may be formed by mechanically breaking down certain plant materials (including nuts, seeds, and legumes) to produce a dispersion of oil bodies and other colloidal matter in water, or by forming oil-in-water emulsions by homogenizing plant-based oils and emulsifiers with water. A brief overview of the formulation and fabrication of plant-based milks is given. The relationship between the optical properties, rheology, and stability of plant-based milks and their composition and structure is then covered. Approaches to fortify these products with micronutrients that may be missing from a plant-based diet are also highlighted. In conclusion, this article highlights how the knowledge of structural design principles can be used to facilitate the creation of higher quality and more sustainable plant-based food products

Surface Modified Carvacrol-rich Satureja khuzestanica Essential Oil Nanoemulsion: A Novel Paclitaxel Formulation Induced Apoptosis on Paclitaxel-Resistant Breast Cancer Cells

Background: The ability of cancer cells to develop multidrug resistance (MDR) is a major challenge in modern chemotherapy. The current generation of commercially available paclitaxel formulations have not been designed to treat resistant tumours. In this study, a nanoemulsion-based delivery system was developed to enhance the efficacy of paclitaxel against resistant breast cancer cells. Methods: The nanoemulsion was formulated using carvacrol-rich Satureja khuzestanica essential oil. Modification of nanoemulsion was performed by incorporating tocopheryl polyethylene glycol 1000 succinate (TPGS) which could inhibit drug resistance in cancer cells. Fabrication of paclitaxel nanoemulsion was performed by high speed homogenization. The cytotoxicity of prepared formulation against resistant breast cancer cells was investigated by MTT assay. Flow cytometry technique was used for cell cycle arrest analysis and examination of the apoptosis induction ability of prepared nanoemulsion. Results: The nanoemulsion had a relatively small mean droplet diameter (93.6 ± 4.2 nm) and good long-term stability. The ability of paclitaxel to inhibit P-gp function in paclitaxel-resistant breast cancer cells (MCF-7/PTX) was synergistically enhanced by administering it within the nanoemulsion. The cytotoxicity of the prepared nanoemulsion on the HUVEC normal cells was much lower than that of MCF-7/PTX cells. Cell cycle analysis utilizing flow cytometry showed that the paclitaxel-loaded nanoemulsion promoted G2-M arrest. Flow cytometry also demonstrated that this nanoemulsion induced apoptosis in MCF-7/PTX cells. Interestingly, apoptosis increased from 20.0% for the free paclitaxel treated group to 85.2 % for the paclitaxel-loaded nanoemulsion treated group. Conclusion: This novel paclitaxel nanoemulsion efficiently suppressed the drug resistance of breast cancer cells and induced effective apoptosis in very low concentrations of paclitaxel

Formulation of More Efficacious Curcumin Delivery Systems Using Colloid Science: Enhanced Solubility, Stability, and Bioavailability

Curcumin is a bioactive constituent isolated from turmeric that has historically been used as a seasoning, pigment, and herbal medicine in food. Recently, it has become one of the most commonly studied nutraceuticals in the pharmaceutical, supplement, and food areas because of its myriad of potential health benefits. For instance, it is claimed to exhibit antioxidant, anti-inflammatory, antimicrobial, antiparasite, and anticancer activities when ingested as a drug, supplement, or food. Toxicity studies suggest that it is safe to consume, even at relatively high levels. Its broad-spectrum biological activities and low toxicity have meant that it has been widely explored as a nutraceutical ingredient for application in functional foods. However, there are several hurdles that formulators must overcome when incorporating curcumin into commercial products, such as its low water solubility (especially under acidic and neutral conditions), chemical instability (especially under neutral and alkaline conditions), rapid metabolism by enzymes in the human body, and limited bioavailability. As a result, only a small fraction of ingested curcumin is actually absorbed into the bloodstream. These hurdles can be at least partially overcome by using encapsulation technologies, which involve trapping the curcumin within small particles. Some of the most commonly used edible microparticles or nanoparticles utilized for this purpose are micelles, liposomes, emulsions, solid lipid particles, and biopolymer particles. Each of these encapsulation technologies has its own benefits and limitations for particular product applications and it is important to select the most appropriate one

Extending Emulsion Functionality: Post-Homogenization Modification of Droplet Properties

Homogenizers are commonly used to produce oil-in-water emulsions that consist of emulsifier-coated oil droplets suspended within an aqueous phase. The functional attributes of emulsions are usually controlled by selecting appropriate ingredients (e.g., surfactants, co-surfactants, oils, solvents, and co-solvents) and processing conditions (e.g., homogenizer type and operating conditions). However, the functional attributes of emulsions can also be tailored after homogenization by manipulating their composition, structure, or physical state. The interfacial properties of lipid droplets can be altered using competitive adsorption or coating methods (such as electrostatic deposition). The physical state of oil droplets can be altered by selecting an oil phase that crystallizes after the emulsion has been formed. The composition of the disperse phase can be altered by mixing different kinds of oil droplets together to induce inter-droplet exchange of oil molecules. The local environment of oil droplets can be altered by embedding them within hydrogel beads. The aggregation state of oil droplets can be controlled by promoting flocculation. These post-homogenization methods can be used to alter functional attributes such as physical stability, rheology, optical properties, chemical degradation, retention/release properties, and/or gastrointestinal fate.Homogenizers are commonly used to produce oil-in-water emulsions that consist of emulsifier-coated oil droplets suspended within an aqueous phase. The functional attributes of emulsions are usually controlled by selecting appropriate ingredients (e.g., surfactants, co-surfactants, oils, solvents, and co-solvents) and processing conditions (e.g., homogenizer type and operating conditions). However, the functional attributes of emulsions can also be tailored after homogenization by manipulating their composition, structure, or physical state. The interfacial properties of lipid droplets can be altered using competitive adsorption or coating methods (such as electrostatic deposition). The physical state of oil droplets can be altered by selecting an oil phase that crystallizes after the emulsion has been formed. The composition of the disperse phase can be altered by mixing different kinds of oil droplets together to induce inter-droplet exchange of oil molecules. The local environment of oil droplets can be altered by embedding them within hydrogel beads. The aggregation state of oil droplets can be controlled by promoting flocculation. These post-homogenization methods can be used to alter functional attributes such as physical stability, rheology, optical properties, chemical degradation, retention/release properties, and/or gastrointestinal fate

Utilization of Nanotechnology to Improve the Handling, Storage and Biocompatibility of Bioactive Lipids in Food Applications

Bioactive lipids, such as fat-soluble vitamins, omega-3 fatty acids, conjugated linoleic acids, carotenoids and phytosterols play an important role in boosting human health and wellbeing. These lipophilic substances cannot be synthesized within the human body, and so people must include them in their diet. There is increasing interest in incorporating these bioactive lipids into functional foods designed to produce certain health benefits, such as anti-inflammatory, antioxidant, anticancer and cholesterol-lowering properties. However, many of these lipids have poor compatibility with food matrices and low bioavailability because of their extremely low water solubility. Moreover, they may also chemically degrade during food storage or inside the human gut because they are exposed to certain stressors, such as high temperatures, oxygen, light, moisture, pH, and digestive/metabolic enzymes, which again reduces their bioavailability. Nanotechnology is a promising technology that can be used to overcome many of these limitations. The aim of this review is to highlight different kinds of nanoscale delivery systems that have been designed to encapsulate and protect bioactive lipids, thereby facilitating their handling, stability, food matrix compatibility, and bioavailability. These systems include nanoemulsions, solid lipid nanoparticles (SLNs), nanostructured lipid carriers (NLCs), nanoliposomes, nanogels, and nano-particle stabilized Pickering emulsions

Segregation Behavior of Polysaccharide-Polysaccharide Mixtures - A Feasability Study

The segregative phase separation behavior of biopolymer mixtures composed entirely of polysaccharides was investigated. First, the electrical, optical, and rheological properties of alginate, modified beet pectin, and unmodified beet pectin solutions were characterized to determine their electrical charge, molecular weight, solubility, and flow behavior. Second, suitable conditions for inducing phase segregation in biopolymer mixtures were established by measuring biopolymer concentrations and segregation times. Third, alginate–beet pectin mixtures were blended at pH 7 to promote segregation and the partitioning of the biopolymers between the upper and lower phases was determined using UV–visible spectrophotometry, colorimetry, and calcium sensitivity measurements. The results revealed that phase separation depended on the overall biopolymer concentration and the degree of biopolymer hydrophobicity. A two-phase system could be formed when modified beet pectins (DE 68%) were used but not when unmodified ones (DE 53%) were used. Our measurements demonstrated that the phase separated systems consisted of a pectin-rich lower phase and an alginate-rich upper phase. These results suggest that novel structures may be formed by utilization of polysaccharide–polysaccharide phase separation. By controlling the product formulation and processing conditions it may therefore be possible to fabricate biopolymer particles with specific dimensions, shapes, and internal structures

Influence of Protein Type on the Antimicrobial Activity of LAE Alone or in Combination with Methylparaben

The cationic surfactant Lauric arginate (LAE) has gained approval for utilization in meat products (limit: 200 mg/kg). However, as for other antimicrobials, its activity is reduced when applied to complex food matrices. The current study therefore aims to better understand protein-antimicrobial agent-interactions and their influence on the antimicrobial activity of (i) LAE and (ii) methylparaben against Listeria innocua and Pseudomonas fluorescens in defined model systems (pH 6). Antimicrobials were utilized alone or in combination with nutrient broth containing either no protein or 2% bovine serum albumin, whey protein isolate, or soy protein hydrolysate. LAE was found to form complexes with all proteins due to electrostatic attraction, determined using microelectrophoretic and turbidity measurements. Minimal lethal concentrations of LAE were remarkably increased (4–13 fold) in the presence of proteins, with globular proteins having the strongest impact. Combinations of LAE (0–200 µg/mL) with the less structure-sensitive component methylparaben (approved concentration 0.1%) remarkably decreased the concentrations of LAE needed to strongly inhibit or even kill both, L. innocua and P. fluorescens in the presence of proteins. The study highlights the importance of ingredient interactions impacting microbial activity that are often not taken into account when examining antimicrobial components having different structure sensitivitie