Emulsion Technology in Nuclear Medicine: Targeted Radionuclide Therapies, Radiosensitizers, and Imaging Agents.

Radiopharmaceuticals serve as a major part of nuclear medicine contributing to both diagnosis and treatment of several diseases, especially cancers. Currently, most radiopharmaceuticals are based on small molecules with targeting ability. However, some concerns over their stability or non-specific interactions leading to off-target localization are among the major challenges that need to be overcome. Emulsion technology has great potential for the fabrication of carrier systems for radiopharmaceuticals. It can be used to create particles with different compositions, structures, sizes, and surface characteristics from a wide range of generally recognized as safe (GRAS) materials, which allows their functionality to be tuned for specific applications. In particular, it is possible to carry out surface modifications to introduce targeting and stealth properties, as well as to control the particle dimensions to manipulate diffusion and penetration properties. Moreover, emulsion preparation methods are usually simple, economic, robust, and scalable, which makes them suitable for medical applications. In this review, we highlight the potential of emulsion technology in nuclear medicine for developing targeted radionuclide therapies, for use as radiosensitizers, and for application in radiotracer delivery in gamma imaging techniques.

Advanced dendritic glucan-derived biomaterials: From molecular structure to versatile applications.

There is considerable interest in the development of advanced biomaterials with improved or novel functionality for diversified applications. Dendritic glucans, such as phytoglycogen and glycogen, are abundant biomaterials with highly branched three-dimensional globular architectures, which endow them with unique structural and functional attributes, including small size, large specific surface area, high water solubility, low viscosity, high water retention, and the availability of numerous modifiable surface groups. Dendritic glucans can be synthesized by in vivo biocatalysis reactions using glucosyl-1-phosphate as a substrate, which can be obtained from plant, animal, or microbial sources. They can also be synthesized by in vitro methods using sucrose or starch as a substrate, which may be more suitable for large-scale industrial production. The large numbers of hydroxyl groups on the surfaces of dendritic glucan provide a platform for diverse derivatizations, including nonreducing end, hydroxyl functionalization, molecular degradation, and conjugation modifications. Due to their unique physicochemical and functional attributes, dendritic glucans have been widely applied in the food, pharmaceutical, biomedical, cosmetic, and chemical industries. For instance, they have been used as delivery systems, adsorbents, tissue engineering scaffolds, biosensors, and bioelectronic components. This article reviews progress in the design, synthesis, and application of dendritic glucans over the past several decades.

Melatonin-based therapeutics for atherosclerotic lesions and beyond: Focusing on macrophage mitophagy.

Atherosclerosis refers to a unique form of chronic proinflammatory anomaly of the vasculature, presented as rupture-prone or occlusive lesions in arteries. In advanced stages, atherosclerosis leads to the onset and development of multiple cardiovascular diseases with lethal consequences. Inflammatory cytokines in atherosclerotic lesions contribute to the exacerbation of atherosclerosis. Pharmacotherapies targeting dyslipidemia, hypercholesterolemia, and neutralizing inflammatory cytokines (TNF-α, IL-1ß, IL-6, IL-17, and IL-12/23) have displayed proven promises although contradictory results. Moreover, adjuvants such as melatonin, a pluripotent agent with proven anti-inflammatory, anti-oxidative and neuroprotective properties, also display potentials in alleviating cytokine secretion in macrophages through mitophagy activation. Here, we share our perspectives on this concept and present melatonin-based therapeutics as a means to modulate mitophagy in macrophages and, thereby, ameliorate atherosclerosis.

Impact of encapsulating a probiotic (Pediococcus pentosaceus Li05) within gastro-responsive microgels on Clostridium difficile infections.

Antibiotic treatment is often followed by Clostridium difficile infection (CDI), which causes severe diarrhea and other health issues. Oral administration of Pediococcus pentosaceus Li05 (Li05) has been shown to have great potential in preventing CDI. However, the viability of Li05 is greatly reduced during storage and passage through the gastrointestinal (GI) tract, which limits its biological activity. In this study, a gastro-responsive microgel was designed to encapsulate and protect Li05 to enhance its efficacy against CDI. The viability of Li05 encapsulated within the microgels was significantly enhanced during long-term storage and after exposure to simulated GI fluids. Moreover, this gastro-responsive microgel led to greater sustained release of the probiotic. In a mouse CDI model, we found that encapsulated Li05 was better at inhibiting C. difficile infection than nonencapsulated Li05, as demonstrated through analysis of the probiotic survival rate, spleen weight, colonic histology, and inflammatory cytokine levels. Moreover, the gut microbial diversity was enriched by treatment with encapsulated Li05. These results suggest that encapsulating Li05 within biopolymer microgels may enhance its ability to prevent and treat CDI using functional foods, supplements, or pharmaceuticals.

Development of food-grade Pickering oil-in-water emulsions: Tailoring functionality using mixtures of cellulose nanocrystals and lauric arginate.

In this study, we investigated the tailoring of food emulsions using interactions between rice bran cellulose nanocrystals (CNCs) and lauric arginate (LAE), which is food-grade cationic surfactant. Complexes of anionic CNCs and cationic LAE (CNCs/LAE) were formed through electrostatic attraction which were characterized using isothermal titration calorimetry (ITC), turbidity, and zeta-potential measurements. The saturation complexes could be formed at ratios of 1:2 (w/w) CNCs-to-LAE. Furthermore, the physical and oxidative stability of oil-in-water emulsions containing lipid droplets coated by CNCs/LAE complexes was determined. Electrostatic complexes formed from 0.02% CNCs and 0.1% LAE produced stable Pickering emulsions that were resistant to droplet coalescence. It was also exhibited that 0.02% CNCs and 0.1% LAE complexes stabilized-emulsions was able to extend the lag phase to 20 days for lipid hydroperoxide and to 14 days for hexanal production. This study shows that food-grade Pickering emulsions with good stability can be produced by CNCs with LAE complexes.

Impact of ripening inhibitors on molecular transport of antimicrobial components from essential oil nanoemulsions.

The objective of this study was to provide insights into the mechanisms involved in the mass transport of antimicrobial compounds from essential oil nanoemulsions to bacterial cell membranes. Origanum oil-in-water nanoemulsions were produced using spontaneous emulsification by titrating a mixture of essential oil, ripening inhibitor, and surfactant (Tween 80) into 5 mM sodium citrate buffer (pH 3.5). Stable nanoemulsions containing relatively small droplets (d < 60 nm) were produced using this low-energy method. The nature of the ripening inhibitor used in the oil phase of the nanoemulsions affected the antimicrobial activity of the nanoemulsions: corn (LCT) > medium-chain triglycerides (MCT). Differences in antimicrobial activity were attributed to the differences in the rate of transfer of hydrophobic antimicrobial constituents from the nanoemulsion to the MCT emulsion, which was used to mimic the hydrophobic region of the bacterial cell membranes. Each antimicrobial nanoemulsion was separated from the MCT emulsion by a dialysis tubing. Dialysis tubing with two different pore sizes was used, one excluding nanoemulsion droplet and micelle delivery, allowing the delivery of antimicrobial compounds only through the aqueous phase and the other by both the aqueous phase and micelles. For origanum oil nanoemulsions, the delivery of all antimicrobial agents occurred more efficiently when micelles were present.

Influence of oat components on lipid digestion using an in vitro model: Impact of viscosity and depletion flocculation mechanism.

Depletion flocculation is a well-known instability mechanism that can occur in oil-in-water emulsions when the concentration of non-adsorbed polysaccharide exceeds a certain level. This critical flocculation concentration depends on the molecular characteristics of the polysaccharide molecules, such as their molecular weight and hydrodynamic radius. In this study, a range of analytical methods (dynamic shear rheology, optical microscopy, and static light-scattering) were used to investigate the interaction between lipid droplets and polysaccharides (guar gum and ß-glucans) of varying weight-average molecular weight and hydrodynamic radius, and concentration. The aim of this work was to see if the health benefits of soluble fibers like ß-glucans could be explained by their influence on the structure and digestibility of lipid emulsions. The apparent viscosity of the emulsions increased with increasing polysaccharide concentration, molecular weight, and hydrodynamic radius. Droplet flocculation was observed in the emulsions only at certain polysaccharide concentrations, which was attributed to a depletion effect. In addition, the water-soluble components in oat flakes, flour, and bran were extracted using aqueous solutions, to examine their impact on emulsion stability and properties. Then, the rate and extent of lipolysis of a sunflower oil-in-water emulsion in the presence of these oat extracts were monitored using the pH-stat method. However, the inhibition of lipolysis was not linearly related to the viscosity of the oat solutions. The water-soluble extracts of ß-glucan collected from oat flakes had a significant inhibitory effect on lipolysis. The results of this study increase our understanding of the possible mechanisms influencing the impact of oat constituents on lipid digestion. This work also highlights the importance of considering the molecular properties of polysaccharides, and not just their impact on solution viscosity.

The Efficacy of Nanoemulsion-Based Delivery to Improve Vitamin D Absorption: Comparison of In Vitro and In Vivo Studies.

SCOPE: Vitamin D (VD) is a fat-soluble vitamin that has a wide range of skeletal and non-skeletal functions. Although it can be synthesized through sun exposure and obtained from fortified foods, VD inadequacy is epidemic worldwide. Therefore innovative strategies are necessary for improving VD status. The present study examined VD absorption via nanoscale delivery systems. METHODS AND RESULTS: We examine the physical characteristics and in vitro bioaccessibility of cholecalciferol (VD3 ) in nanoemulsion using a simulated gastrointestinal tract system. To evaluate the in vivo bioavailability, we orally administer three groups of mice with VD3 nanoemulsion, VD3 coarse emulsion, or vehicle nanoemulsion without VD3 , and the serum 25(OH)D3 is measured using radioactive immunoassay. The nanoemulsion-based delivery system increases the in vitro bioaccessibility by 3.94-folds (p < 0.05), as indicated by the concentration of vitamin D3 in micelles. Our animal study shows that, when compared to the vehicle group, the coarse emulsion numerically increases the serum 25(OH)D3 by 36%, whereas the nanoemulsion statistically significantly increases the serum 25(OH)D3 by 73% (p < 0.01). CONCLUSION: Our findings indicate that a nanoemulsion-based delivery system is a promising approach to improve VD bioavailability, and further studies are warranted to determine its efficacy in humans.

Effect of ripening inhibitor type on formation, stability, and antimicrobial activity of thyme oil nanoemulsion.

The objective of this research was to study the impact of ripening inhibitor level and type on the formation, stability, and activity of antimicrobial thyme oil nanoemulsions formed by spontaneous emulsification. Oil-in-water antimicrobial nanoemulsions (10 wt%) were formed by titrating a mixture of essential oil, ripening inhibitor, and surfactant (Tween 80) into 5 mM sodium citrate buffer (pH 3.5). Stable nanoemulsions containing small droplets (d < 70 nm) were formed. The antimicrobial activity of the nanoemulsions decreased with increasing ripening inhibitor concentration which was attributed to a reduction in the amount of hydrophobic antimicrobial constituents transferred to the separated hydrophobic domain, mimicking bacterial cell membranes, by using dialysis and chromatography. The antimicrobial activity of the nanoemulsions also depended on the nature of the ripening inhibitor used: palm ≈ corn > canola > coconut which also depended on their ability to transfer hydrophobic antimicrobial constituents to the separated hydrophobic domain.

Correction: Microencapsulation of probiotics in hydrogel particles: enhancing Lactococcus lactis subsp. cremoris LM0230 viability using calcium alginate beads.

Correction for 'Microencapsulation of probiotics in hydrogel particles: enhancing Lactococcus lactis subsp. cremoris LM0230 viability using calcium alginate beads' by Timothy W. Yeung et al., Food Funct., 2016, 7, 1797-1804.

Microencapsulation in Alginate and Chitosan Microgels to Enhance Viability of Bifidobacterium longum for Oral Delivery.

Probiotic microorganisms are incorporated into a wide variety of foods, supplements, and pharmaceuticals to promote human health and wellness. However, maintaining bacterial cell viability during storage and gastrointestinal transit remains a challenge. Encapsulation of bifidobacteria within food-grade hydrogel particles potentially mitigates their sensitivity to environmental stresses. In this study, Bifidobacterium longum subspecies and strains were encapsulated in core-shell microgels consisting of an alginate core and a microgel shell. Encapsulated obligate anaerobes Bifidobacterium longum subsp. infantis and Bifidobacterium longum subsp. longum exhibited differences in viability in a strain-dependent manner, without a discernable relationship to subspecies lineage. This includes viability under aerobic storage conditions and modeled gastrointestinal tract conditions. Coating alginate microgels with chitosan did not improve viability compared to cells encapsulated in alginate microgels alone, suggesting that modifying the surface charge alone does not enhance delivery. Thus hydrogel beads have great potential for improving the stability and efficacy of bifidobacterial probiotics in various nutritional interventions.

Microencapsulation of probiotics in hydrogel particles: enhancing Lactococcus lactis subsp. cremoris LM0230 viability using calcium alginate beads.

Probiotics are beneficial microbes often added to food products to enhance the health and wellness of consumers. A major limitation to producing efficacious functional foods containing probiotic cells is their tendency to lose viability during storage and gastrointestinal transit. In this study, the impact of encapsulating probiotics within food-grade hydrogel particles to mitigate sensitivity to environmental stresses was examined. Confocal fluorescence microscopy confirmed that Lactococcus lactis were trapped within calcium alginate beads formed by dripping a probiotic-alginate mixture into a calcium solution. Encapsulation improved the viability of the probiotics during aerobic storage: after seven days, less than a two-log reduction was observed in encapsulated cells stored at room temperature, demonstrating that a high concentration of cells survived relative to non-encapsulated bacteria. These hydrogel beads may have applications for improving the stability and efficacy of probiotics in functional foods.

Formation, antioxidant property and oxidative stability of cold pressed rice bran oil emulsion.

Cold pressed rice bran oil (CPRBO) is used in foods, cosmetics, and pharmaceuticals due to its desirable health and functional attributes. The purpose of this work was to study the formation, antioxidant property and oxidative stability of oil-in-water emulsion of CPRBO. The influence of oil (10-40 % CPRBO) and surfactant (1-5 % glyceryl monostearate (GMS)) concentration on the properties of emulsions were studied. The lightness (L*) and yellowness (b*) of CPRBO emulsions decreased as GMS concentration increased, which was attributed to a decrease in droplet size after homogenization. The CPRBO emulsion was stable during storage at room temperature for 30 days. Increasing the oil concentration in the CPRBO emulsions increased their antioxidant activity, which can be attributed to the corresponding increase in phytochemical content. However, GMS concentration had little impact on the antioxidant activity of CPRBO emulsions. The storage of CPRBO emulsion at room temperature showed that lipid oxidation markers gradually increased after 30 days of storage, which was correlated to a decrease in gamma oryzanol content and antioxidant activity. These results have important implications for the utilization of rice bran oil (RBO) as a function ingredient in food, cosmetic, and pharmaceutical products.

Fluorescence quenching study of resveratrol binding to zein and gliadin: Towards a more rational approach to resveratrol encapsulation using water-insoluble proteins.

Several health benefits have been ascribed to consumption of resveratrol, a polyphenol that can be extracted from grape skins. However, its use as a nutraceutical ingredient is compromised by its low water solubility, chemical stability, and bioavailability. Encapsulation of resveratrol in protein nanoparticles can be used to overcome these issues. Fluorescence quenching experiments were used to study the interaction of resveratrol with gliadin and zein. Resveratrol interacted with both proteins, but the binding constant was higher for zein than for gliadin at 35 °C. Furthermore, binding between resveratrol and gliadin increased at higher temperatures, which was not observed for zein. Analysis of the thermodynamic parameters suggested that resveratrol-gliadin binding mainly occurs through hydrophobic interactions while the binding with zein is predominantly mediated through hydrogen bonds. These results help rationalise ingredient selection and production of protein nanoparticles and microparticles for encapsulation, protection and release of resveratrol and potentially other bioactive compounds.

Reduced-fat foods: the complex science of developing diet-based strategies for tackling overweight and obesity.

Fat plays multiple roles in determining the desirable physicochemical properties, sensory attributes, nutritional profile, and biologic response of food products. Overconsumption of fats is linked to chronic diseases, such as obesity, coronary heart disease, diabetes, and cancer. There is therefore a need to develop reduced-fat products with physicochemical properties and sensory profiles that match those of their full-fat counterparts. In addition, foods may be redesigned to increase the feelings of satiety and satiation, and thereby reduce overall food intake. The successful design of these types of functional foods requires a good understanding of the numerous roles that fat plays in determining food attributes and the development of effective strategies to replace these attributes. This article provides an overview of the current understanding of the influence of fat on the physicochemical and physiologic attributes of emulsion-based food products and highlights approaches to create high-quality foods with reduced-fat contents.

Emulsifying and emulsion-stabilizing properties of gluten hydrolysates.

Gluten is produced as a coproduct of the wheat starch isolation process. In this study, gluten was hydrolyzed to degrees of hydrolysis (DH) of 3-6-10 and 1-2-3 with alcalase and trypsin, respectively. These peptidases have a clearly distinct substrate specificity. Corn oil-in-water emulsions (10 wt % oil) were prepared by high-pressure homogenization at pH 7.5. Gluten peptides with DH 3 proved to be the most effective in producing peptides displaying emulsifying properties. Higher levels of alcalase hydrolysates (2.0 wt %) than of trypsin hydrolysates (1.0 wt %) were required to produce stable emulsions with small droplet sizes, which is attributed to differences in the nature of the peptides formed. The emulsions had small mean droplet diameters (d32 < 1000 nm). Emulsions produced with trypsin hydrolysates (stable after 9 days at 55 °C) displayed better thermal stability compared to those produced with alcalase hydrolysates (destabilized after 2 days at 37 °C). The hydrolysate-containing emulsions, however, were quickly destabilized by salt addition (≤100 mM NaCl) and when the pH approached the isoelectric point of the coated droplets (pH ~5.5). Microscopic analysis revealed the formation of air-in-oil-in-water emulsions at lower hydrolysate concentrations, whereas at higher concentrations (≥3.0 wt %) extensive flocculation occurred. Both phenomena contributed to creaming of the emulsions. These results may be useful for the utilization of gluten hydrolysates in food and beverage products.

Interaction of a food-grade cationic surfactant (lauric arginate) with food-grade biopolymers (pectin, carrageenan, xanthan, alginate, dextran, and chitosan).

Lauric arginate (LAE) is a food-grade cationic surfactant that is a highly potent antimicrobial active against a wide range of food pathogens and spoilage organisms. In compositionally complex environments, the antimicrobial activity of cationic LAE is likely to be impacted by its interactions with other charged components. The purpose of this study was to characterize the interactions between cationic LAE and various food grade biopolymers with different charge characteristics: anionic (pectin, alginate, carrageenan, xanthan), neutral (dextran), and cationic (chitosan). Isothermal titration calorimetry (ITC) and turbidity measurements were used to characterize surfactant-biopolymer interactions and the solubility of any aggregates formed. ITC and turbidity measurements suggested that no complex formation occurred between the cationic LAE and the cationic or neutral biopolymers, although the critical micelle concentration (cmc) of the surfactant was changed because of excluded volume effects. On the other hand, ITC measurements indicated a strong binding interaction between cationic LAE and anionic biopolymers. The amount of surfactant bound and the solubility of the aggregates formed depended strongly on biopolymer type. The results of this study have important implications for the application of LAE in compositionally complex systems.

Stabilization of model beverage cloud emulsions using protein-polysaccharide electrostatic complexes formed at the oil-water interface.

The potential of utilizing interfacial complexes, formed through the electrostatic interactions of proteins and polysaccharides at oil-water interfaces, to stabilize model beverage cloud emulsions has been examined. These interfacial complexes were formed by mixing charged polysaccharides with oil-in-water emulsions containing oppositely charged protein-coated oil droplets. Model beverage emulsions were prepared that consisted of 0.1 wt % corn oil droplets coated by beta-lactoglobulin (beta-Lg), beta-Lg/alginate, beta-Lg/iota-carrageenan, or beta-Lg/gum arabic interfacial layers (pH 3 or 4). Stable emulsions were formed when the polysaccharide concentration was sufficient to saturate the protein-coated droplets. The emulsions were subjected to variations in pH (from 3 to 7), ionic strength (from 0 to 250 mM NaCl), and thermal processing (from 30 or 90 degrees C), and the influence on their stability was determined. The emulsions containing alginate and carrageenan had the best stability to ionic strength and thermal processing. This study shows that the controlled formation of protein-polysaccharide complexes at droplet surfaces may be used to produce stable beverage emulsions, which may have important implications for industrial applications.

Influence of pH and ionic strength on formation and stability of emulsions containing oil droplets coated by beta-lactoglobulin-alginate interfaces.

Emulsions of 0.1 wt % corn oil-in-water containing oil droplets coated by beta-lactoglobulin (0.009 wt % beta-Lg, 5 mM phosphate buffer, pH 7.0) were prepared in the absence and presence of sodium alginate (0 or 0.004 wt %). The pH (3-7) and ionic strength (0-250 mM NaCl) of these emulsions were adjusted, and the particle charge, particle size, and creaming stability were measured. Alginate adsorbed to the beta-Lg-coated droplets from pH 3 to 6, which was attributed to electrostatic attraction between the anionic polymer and cationic patches on the droplet surfaces. Droplets coated by beta-Lg-alginate had better stability to flocculation than those coated by beta-Lg alone, especially around the isoelectric point of the adsorbed proteins and at low ionic strengths (< 100 mM NaCl). At pH 5, alginate molecules desorbed from the droplet surfaces at high salt concentrations due to weakening of the electrostatic attraction.

Two-dimensional rotating-frame Overhauser spectroscopy (ROESY) and (13)C NMR study of the interactions between maltodextrin and an anionic surfactant.

Rotational frame nuclear Overhauser effect spectroscopy (ROESY) and (13)C NMR measurements were carried out to study the molecular interaction between maltodextrin, a digestive byproduct of starch, and an anionic surfactant. Significant differences in chemical shifts were observed when sodium dodecyl sulfate (SDS) was introduced into the maltodextrin (DE 10) solutions. (13)C NMR measurement indicated that there were downfield shifts and broadening of peaks, especially in the region of 75-81 and 100-103 ppm, which were assigned to carbons 1 and 4 of the d-glucopyranose residues of maltodextrin, respectively. ROESY spectra indicated cross-peaks between the SDS and maltodextrin protons. These peaks can arise only in the case of the designated SDS protons and maltodextrin protons being less than 0.5 nm apart for a substantial period of time. The most intense cross-peaks are those between the central CH(2) protons of SDS near 1.2 ppm and the maltodextrin protons ranging from 3.5 to 3.9 ppm. The SDS-H3 CH(2) protons were resolved from the bulk of the SDS protons, with peaks and shoulders at 1.25 ppm, which indicated an especially strong interaction of the SDS hydrophobic tail with MD6 and some less intense interactions with MD2, 4, and 5.