Metal-organic frameworks-based moisture responsive essential oil hydrogel beads for fresh-cut pineapple preservation.

The preservation of fresh-cut fruits and vegetables has attracted attention to the shelf-life reduction caused by high humidity. Herein, alginate/copper ions cross-linking, in-situ growth and self-assembly techniques of metal-organic frameworks (MOFs) were utilized to prepare a moisture responsive hydrogel bead (HKUST-1@ALG). As the multistage porous structure formation, tea tree essential oil (TTO) load capacity in hydrogel bead (TTO-HKUST-1@ALG) was increased from 6.1% to 21.6%. TTO-HKUST-1@ALG had excellent moisture response performance, and the release rates of TTO increased from 33.89% to 70.98% with moisture increasing from 45% to 95%. Besides, TTO-HKUST-1@ALG exhibited excellent antimicrobial, antioxidant capacity, and biocompatibility. During storage, TTO-HKUST-1@ALG effectively improved the cell membrane integrity by maintaining the balance of reactive oxygen species metabolism. The degradation of cell wall structure and tissue softening were delayed by inhibiting the cell wall-degrading enzymes activity. Briefly, TTO-HKUST-1@ALG improved the storage quality and extended shelf-life of fresh-cut pineapple, which was a promising preservative.

The improvement of water barrier property in gelatin/carboxymethyl cellulose composite film by electrostatic interaction regulation and its application in strawberry preservation.

Gelatin (GL) and carboxymethyl cellulose (CMC) are common natural components for edible films, but their water barrier performance are finite as hydrophilic polymers. In this study, a GL/CMC water barrier film was prepared, characterized and applied. The microstructure results showed that complex coacervation at pH 2.0 and cross-linking effect of sodium benzoate resulted in strong interaction forces and dense structure of this film. Compared with pure GL or CMC film, this novel composite film decreased water vapor permeability by approximately 90%, and possessed applicable water solubility (51.5%) and stronger barrier to oxygen and UV light. Acidic environment and sodium benzoate endowed antibacterial activity. Furthermore, the water barrier coating film decreased water loss by 47.8% and improved overall quality of fresh strawberries stored at 25 °C for 6 d. Therefore, the novel water barrier film based on complex coacervation and cross-linking is promising to control the postharvest quality of perishable berries.

Inhibition of cinnamic acid and its derivatives on polyphenol oxidase: Effect of inhibitor carboxyl group and system pH.

Phenolic acids are promising inhibitors of polyphenol oxidase (PPO), but the effects of carboxyl group and pH on their inhibition effects are still unclear. In this study, methyl cinnamate, cinnamic acid and 4-carboxycinnamic acid were investigated by their inhibitory effects with pH varied from 6.8 to 5.0. Results showed that 4-carboxycinnamic acid had the strongest inhibitory effect on PPO, followed by cinnamic acid and methyl cinnamate. Acidic pH enhanced the inhibitory effects of cinnamic acid and its derivatives on PPO, and the enhancement degree, IC50 and Ki declining degree were followed as 4-carboxycinnamic acid > cinnamic acid > methyl cinnamate. Methyl cinnamate exhibited competitive inhibition on PPO, while cinnamic acid and 4-carboxycinnamic acid exhibited mixed-type inhibition. Inhibitors induced slight changes in the secondary and tertiary structures of PPO, which were enhanced by acidic pH. Molecular docking results showed that 4-carboxycinnamic acid exhibited the strongest binding ability, and the main interaction forces were around carboxyl groups, and acidic pH enhanced the binding effect through more interactions and lower binding energy. This study could provide new insights into industrial application of cinnamic acid and its derivatives for the control of enzymatic browning of fruits and vegetables.

Construction of curcumin-fortified juices using their self-derived extracellular vesicles as natural delivery systems: grape, tomato, and orange juices.

Different fruit and vegetable juices were first used to encapsulate curcumin to improve its solubility, stability, and bioaccessibility, which is expected to enable designing of polyphenol-enriched beverages and impact human health and well-being. Briefly, fruit and vegetable-derived extracellular vesicles usually serve as transport and communication tools between different cells, which means they also may be utilized as delivery carriers for other bioactive agents. Curcumin, as a model polyphenol with many physiological activities, typically has low water-solubility, stability, and bioaccessibility. Therefore, extracellular vesicles were applied to load curcumin to overcome these challenges and to facilitate its incorporation into fruit and vegetable juices. Three kinds of curcumin-loaded fruit and vegetable juices, including curcumin-loaded grape (Cur-G), tomato (Cur-T), and orange (Cur-O) juices, exhibited higher encapsulation efficiency (>80%) than others. The patterns of XRD and FTIR confirmed that curcumin moved into extracellular vesicles in the amorphous form and that the hydrogen bonding force was found between them. Three kinds of fruit and vegetable juices can significantly enhance the solubility, stability and bioavailability of curcumin, but the degrees of improvement are different. For instance, Cur-O exhibited the highest encapsulation efficiency, chemical stability, and effective bioaccessibility than Cur-G and Cur-T. In summary, this study shows that natural fruit and vegetable juices can effectively improve the solubility, stability and bioaccessibility of active polyphenols, which is expected to enable successful designing of nutrient-enriched beverages with a simple method according to various needs of people and be directly applied to food processing and home production.

Improving shikonin solubility and stability by encapsulation in natural surfactant-coated shikonin nanoparticles.

It is significant to develop a colloidal delivery system to improve the water solubility, stability, and bioavailability of shikonin, which is a hydrophobic plant polyphenol with a variety of physiological activities. In this study, three kinds of natural surfactants (saponin, sophorolipid, and rhamnolipid) were used to prepare shikonin nanoparticles by the pH-driven method. The physicochemical and structural properties of the shikonin nanoparticles were characterized, including particle size, zeta potential, and morphology. The encapsulation efficiencies of shikonin nanoparticles coated with saponin and sophorolipid were 97.6% and 97.3%, respectively, which were much higher than that of rhamnolipid-coated shikonin nanoparticles (19.0%). Shikonin nanoparticles coated with saponin and sophorolipid showed good resistance to heat and light and maintained long-term stability during storage. Moreover, shikonin nanoparticles coated with saponin and sophorolipid improved their in vitro-bioavailability. PRACTICAL APPLICATION: These article results are of great importance for improving the stability and bioavailability of shikonin in functional foods, dietary supplements, or pharmaceutical preparations. Moreover, this study provided theoretical and practical guides for further research of shikonin nanoparticles and may promote the development of natural colloidal delivery systems.

Hydrogels assembled from hybrid of whey protein amyloid fibrils and gliadin nanoparticles for curcumin loading: Microstructure, tunable viscoelasticity, and stability.

Food grade hydrogel has become an ideal delivery system for bioactive substances and attracted wide attention. Hybrids of whey protein isolate amyloid fibrils (WPF) and gliadin nanoparticles (GNP) were able to assemble into WPF-GNP hydrogel at a low protein concentration of 2 wt%, among which WPF and GNP were fabricated from the hydrolysis of whey protein isolate under 85°C water bath (pH 2.0) and antisolvent precipitation, respectively. Atomic force microscope (AFM) images indicated that the ordered nanofibrillar network of WPF was formed at pH 2.0 with a thickness of about 10 nm. Cryo-SEM suggested that WPF-GNP hydrogel could arrest GNP within the fibrous reticular structure of the partially deformed WPF, while the hybrids of native whey protein isolate (WPI) and GNP (WPI-GNP hybrids) only led to protein aggregates. WPF-GNP hydrogel formed at pH 4.0 (85°C, 3 h, WPF:GNP = 4:1) possessed the largest elastic modulus (G' = 419 Pa), which far exceeded the elastic modulus of the WPI-GNP hybrids (G' = 16.3 Pa). The presence of NaCl could enhance the strength of WPF-GNP hydrogel and the largest value was achieved at 100 mM NaCl (∼105 mPa) in the range of 0∼500 mM due to electrostatic screening. Moreover, WPF-GNP hydrogel showed a high encapsulation efficiency for curcumin, 89.76, 89.26, 89.02, 85.87, and 79.24% for pH 2.0, 3.0, 4.0, 5.0, and 6.0, respectively, which suggested that the formed hydrogel possess good potential as a delivery system. WPF-GNP hydrogel also exhibited a good protection effect on the photodegradation stability of the loaded curcumin with the retention of up to 75.18% after hydrogel was exposed to ultraviolet radiation for 7 days. These results suggested that the viscoelasticity of WPF-GNP hydrogel was tunable via pH-, ion-, or composition-adjustment and the hydrogel showed excellent protection on the thermal and photodegradation stability of curcumin.

Improving Anti-listeria Activity of Thymol Emulsions by Adding Lauric Acid.

In this study, a novel emulsion, thymol (Thy) and lauric acid (LA) emulsion (Thy/LA-Emulsion) was prepared by homogenizing eutectic solvent (Thy/LA mixture) and caseinate solution. The effects of different thymol and lauric acid mass ratio on the formation, stability, and antibacterial activity of emulsions were studied. Compared with thymol alone, adding lauric acid (25, 50, and 75%) could enhance the antibacterial efficacy of the emulsions. Among them, Thy/LA25%-Emulsion could be stored at room temperature for a month without the increase of particle size, indicating that the addition of LA had not impacted the stability of emulsions. Meanwhile, Thy/LA25%-Emulsion exhibited a greater inhibition zone (3.06 ± 0.12 cm) and required a lower concentration (0.125 mg/mL) to completely inhibit the growth of Listeria monocytogenes. Consequently, Thy/LA25%-Emulsion demonstrated the best antibacterial activity and physicochemical stability due to its long-term storage stability. Our results suggest that Thy/LA25%-Emulsion may become a more functional natural antibacterial agent with greater commercial potential owing to its cheaper raw materials, simpler production processes, and better antibacterial effect in the food industry.

Improving norbixin dispersibility and stability by liposomal encapsulation using the pH-driven method.

BACKGROUND: Norbixin, a carotenoid extracted from annatto seeds, is widely utilized as a natural pigment in foods, cosmetics and medicines. Its water solubility is relatively high under neutral or alkaline conditions but low under acidic conditions, which limits its application in some food products. RESULTS: This problem was overcome by utilizing liposomes to encapsulate the carotenoids so that they could be easily dispersed within acidic solutions. The norbixin was loaded into the liposomes using the pH-driven method. Liposomes were produced by passing aqueous phospholipid dispersions through a microfluidizer under high pressure. Norbixin was then added to the liposome dispersions at pH 7.0 and then driven into the hydrophobic domains of the phospholipid bilayers by acidifying the system. Measurements of the encapsulation efficiency showed that the norbixin was successfully loaded into the liposomes using the pH-driven method. X-ray diffraction analysis showed that the norbixin was in an amorphous state after incorporation into the liposomes. Encapsulation of norbixin within the liposomes was also shown to increase its water dispersibility and chemical stability under acidic pH conditions. CONCLUSION: The pH-driven method therefore provides a useful means of increasing the application of this bioactive carotenoid within functional foods and other products. © 2021 Society of Chemical Industry.

Fabrication of Caseinate Stabilized Thymol Nanosuspensions via the pH-Driven Method: Enhancement in Water Solubility of Thymol.

Thymol has been applied as a spice and antibacterial agent in commercial products. However, the utilization of thymol in the food and pharmaceutical field has recently been limited by its poor water solubility and stability. In this work, a caseinate-stabilized thymol nanosuspension was fabricated by pH-driven methods to overcome those limitations. Firstly, the chemical stability of thymol at different pH value conditions was investigated. The physiochemical properties of thymol nanosuspensions were then characterized, such as average particle size, zeta potential, encapsulation efficiency, and loading capacity. Meanwhile, the X-ray diffraction results showed that thymol was present as an amorphous state in the nanosuspensions. The thermal stability of thymol was slightly enhanced by encapsulation through this process, and the thymol nanosuspensions were stable during the long-term storage, and the average particle size of nanosuspensions showed that there was no aggregation of nanosuspensions during storage and high temperature. Finally, the antimicrobial activity of thymol nanosuspensions was evaluated by investigating the minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) against Salmomella enterca, Staphlococcus aureus, Escherichia coli, and Listeria monocytogenes. These results could provide useful information and implications for promoting the application of thymol in food, cosmetic, and pharmaceutical commercial products.

Enhancing the oxidative stability of algal oil emulsions by adding sweet orange oil: Effect of essential oil concentration.

The effects of sweet orange essential oil (SOEO) concentration (0-12.5% of oil phase) on the physical stability, oxidative stability, and interfacial composition of algal oil-in-water emulsions containing sodium caseinate-coated oil droplets was examined. SOEO addition had no influence on the microstructure and physical stability of the algal oil emulsions. The addition of SOEO enhanced the oxidation stability of algal oil emulsion. As an example, the values of algal oil emulsions with 0 and 10% SOEO were 198 and 100 mmol/kg algal oil after 16 days of accelerated oxidation, respectively. The absorbed protein level was higher in the algal oil emulsion containing 10% SOEO (70%) than in 0% SOEO (57%). This result suggested that the presence of SOEO enhanced the interfacial thickness, possibly by interacting with the casein molecules. A thicker protein layer may have helped to retard the oxidation of the omega-3 oils inside lipid droplets.

Gliadin Nanoparticles Pickering Emulgels for ß-Carotene Delivery: Effect of Particle Concentration on the Stability and Bioaccessibility.

ß-carotene is a promising natural active ingredient for optimum human health. However, the insolubility in water, low oral bioavailability, and instability in oxygen, heat, and light are key factors to limit its application as incorporation into functional foods. Therefore, gliadin nanoparticles (GNPs) Pickering emulgels were chosen as food-grade ß-carotene delivery systems. The objectives of the present study were to investigate the influence of GNPs concentration on the rheological properties, stability, and simulated gastrointestinal fate of ß-carotene of Pickering emulgels. The formulations of Pickering emulgels at low GNPs concentration had better fluidity, whereas at high GNPs concentration, they had stronger gel structures. Furthermore, the thermal stability of ß-carotene loaded in Pickering emulgels after two pasteurization treatments was significantly improved with the increase of GNPs concentration. The Pickering emulgels stabilized with higher GNPs concentration could improve the protection and bioaccessibility of ß-carotene after different storage conditions. This study demonstrated the tremendous potential of GNPs Pickering emulgels to carry ß-carotene.

Novel folated pluronic F127 modified liposomes for delivery of curcumin: preparation, release, and cytotoxicity.

Aim: A novel folated pluronic F127 (FA-F127) was synthesised, so as to modify liposomes with FA group on the surface, and evaluate the effects of FA-F127 modification on the properties of the modified liposomes.Methods: FA was linked to one end of pluronic F127, via the terminal OH group, to obtain FA-F127 and the structure was characterised. FA-F127 modified curcumin liposomes (cur-FA-F127-Lps) were prepared. The physicochemical characteristics of cur-FA-F127-Lps, including morphology and particle size, were studied. The in vitro cytotoxicity of cur-FA-F127-Lps against KB cancer cells was determined by MTT tests.Results: The effects of FA-F127 modification on the average particle size, PDI, curcumin encapsulation efficiency and microstructure were not significant. Compared with nonfolated F127 liposomes (cur-F127-Lps), cur-FA-F127-Lps exhibited significantly higher cytotoxicity towards KB cells.Conclusions: Folic acid modified liposomes provide a novel strategy to improve the chemotherapeutic efficacy of hydrophobic bioactive compounds.

Influence of ionic strength and thermal pretreatment on the freeze-thaw stability of Pickering emulsion gels.

Salt addition and thermal pretreatment were used to improve the freeze-thaw stability of Pickering emulsion gels (PEGs) stabilized by compound proteins. Thermal pretreatment with the presence of salt could promote the formation of gel-like structure and alter the interactions between the emulsion droplets of PEGs, sequentially increase the resistance of the PEGs to water separation, creaming, and oiling-off during freeze-thaw cycles (freeze at -20 °C for 22 h and thawing at 37 °C for 2 h), especially at higher salt levels (200 and 500 mM). Microstructures indicated that the presence of high salt concentration and heat pretreatment could help to maintain the gel-like structures of PEGs during freeze-thaw cycles. Overall, our results showed that novel viscoelastic food materials with good freeze-thaw stability can be produced by controlling the electrostatic interactions between the emulsion droplets and the gelation of emulsion gels. These materials may be useful for application in frozen food products.

Improvement on stability, loading capacity and sustained release of rhamnolipids modified curcumin liposomes.

A novel cholesterol-free curcumin delivery system was fabricated by rhamnolipids modified liposomes (RL-Lps). The incorporation of the rhamnolipids increased the sphericity, reduced the size, and decreased the polydispersity of the liposomes compared with pure liposomes (Lps). Analysis of the environmental stability of the RL-Lps showed they have good long-term stability over a wide range of pH (2-3 and 5-8), ionic strengths (0-200 mM), and accelerated centrifugal conditions. The curcumin-loaded rhamnolipids modified liposomes (Cur-RL-Lps) could be prepared with a relatively high loading efficiency (LE > 90%) and loading capacity (LC > 3.5%). The thermal and photochemical stability of the curcumin was improved after encapsulation in the Cur-RL-Lps. In vitro release studies indicated that the sustained release of the curcumin was prolonged when rhamnolipids were incorporated into the liposomes. This study shows that rhamnolipids have great potential for liposomal delivery system suitable for utilization in functional foods, dietary supplements, and pharmaceutical preparations.

Impact of curcumin delivery system format on bioaccessibility: nanocrystals, nanoemulsion droplets, and natural oil bodies.

Curcumin, a hydrophobic yellow-orange crystalline substance derived from plants, is claimed to exhibit a broad range of biological activities. Its application in functional foods and beverages is often limited by its low solubility in aqueous media, chemical instability, and low bioavailability. Previously, we have shown that curcumin can be successfully loaded into emulsions using the pH-shift method. In this study, we compared the efficacy of curcumin crystals dispersed in water (control) with three delivery systems produced using the pH-shift method: curcumin nanocrystals; curcumin-loaded nanoemulsions; and curcumin-loaded soy oil bodies. The nanoemulsions and oil bodies formed creamy yellow dispersions that were stable to creaming, whereas the nanocrystals formed a cloudy yellow-orange suspension that was prone to sedimentation. The gastrointestinal fate of the delivery systems was assessed using a static in vitro digestion model consisting of mouth, stomach, and small intestine phases. The nanoemulsions and oil bodies were rapidly and fully digested, while the nanocrystals were not. All three systems were relatively stable to chemical transformation in the in vitro digestion model. The nanocrystals gave a low bioaccessibility but the other two systems gave a high bioaccessibility, which was attributed to their ability to form mixed micelles to solubilize the curcumin. These results have important implications for the creation of more effective delivery systems for curcumin.

Formation and characterization of oil-in-water emulsions stabilized by polyphenol-polysaccharide complexes: Tannic acid and ß-glucan.

Oil-in-water emulsions were prepared that were stabilized by a polyphenol (tannic acid, TA) and/or a polysaccharide (ß-glucan, BG). The influence of TA concentration and solution pH on the physical stability and microstructure of the emulsions was investigated. Emulsions formed using only BG (1%) contained large droplets that were unstable to flocculation and coalescence. The stability of the emulsions (pH 5) could be enhanced by optimizing the ratio of TA-to-BG used to form them, i.e., TA/BG = 0.4 or 0.5. This effect was attributed to a combination of increased steric hindrance and reduced hydrogen bonding of TA to BG. Transmission electron microscopy (TEM) indicated that increasing the level of TA present increased the compactness and thickness of the TA-BG interfacial layers formed around the oil droplets. Furthermore, the stability of the emulsions to droplet flocculation and coalescence depended on the TA/BG ratio and solution pH. The impact of environmental conditions on emulsion stability was also investigated. Emulsions stabilized by TA-BG complexes (TA/BG = 0.5) remained stable from pH 5 to 9 at ambient temperature and at temperatures ≤60 °C at pH 5, but were highly unstable to salt addition at pH 5. Our results may increase the breadth of applications of ß-glucan as a functional ingredient in foods.

Encapsulation of Lipophilic Polyphenols into Nanoliposomes Using pH-Driven Method: Advantages and Disadvantages.

The poor water solubility and oral bioavailability of many lipophilic polyphenols can be improved through the use of colloidal delivery systems. In this study, a pH-driven method was used to encapsulate curcumin, quercetin, and resveratrol within nanoliposomes. This method is based on the decrease in water-solubility of certain polyphenols when they move from alkaline to acid conditions. However, the chemical stability of some polyphenols is relatively poor under alkaline conditions. For this reason, the impact of pH on the chemical degradation of the three polyphenols was studied. The polyphenols were then encapsulated within nanoliposomes using the pH-driven method and the encapsulation efficiency (EE) and chemical stability were determined. The EE of curcumin, quercetin, and resveratrol in the nanoliposomes was 100, 54, and 93%, respectively. Differences in the EE were mainly attributed to differences in their stability under alkaline conditions. Our results show that the application of this method to other lipophilic polyphenols depends on the impact of pH on their solubility and chemical stability, which needs to be established on a case-by-case basis.

Role of Mucin in Behavior of Food-Grade TiO2 Nanoparticles under Simulated Oral Conditions.

Fine titanium dioxide (TiO2) particles have been used as additives (E171) to modify the optical properties of foods and beverages for many years. Commercial TiO2 additives, however, often contain a significant fraction of nanoparticles (diameter <100 nm), which has led to some concern about their potentially adverse health effects. At present, relatively little is known about how the characteristics of TiO2 particles are altered as they travel through the human gastrointestinal tract. Alterations in their electrical characteristics, surface composition, or aggregation state would be expected to alter their gastrointestinal fate. The main focus of this study was, therefore, to characterize the behavior of TiO2 particles under simulated oral conditions. Changes in the aggregation state and electrical characteristics were monitored using particle size, ζ-potential, turbidity, and electron microscopy measurements, whereas information about mucin-particle interactions were obtained using isothermal titration calorimetry and surface-enhanced Raman spectroscopy. Our results indicate that there was a strong interaction between TiO2 and mucin: mucin absorbed to the surfaces of the TiO2 particles and reduced their tendency to aggregate. The information obtained in this study is useful for better understanding the gastrointestinal fate and potential toxicity of ingested inorganic particles.

Fabrication and Characterization of Curcumin-Loaded Liposomes Formed from Sunflower Lecithin: Impact of Composition and Environmental Stress.

There is significant interest in the formulation of liposome-based delivery systems using cheap plant-based commercial sources of lecithin. This study evaluated the impact of phospholipid type on the formation, stability, and curcumin-loading of sunflower liposomes. Four kinds of sunflower lecithin (Sunlipon 50, 65, 75, and 90) with different phosphatidylcholine (PC) levels were used to prepare the liposomes using microfluidization. The particle size, surface charge, microstructure, and stability of the liposomes were determined. All four kinds of lecithin were suitable for fabricating stable liposomes regardless of the PC content. Curcumin was loaded into the liposomes using a newly developed pH-driven method. The loading capacity and heat stability of curcumin increased as the PC content of the lecithin increased. These results showed that commercial plant-based lecithins may be suitable for overcoming some of the hurdles normally associated with using liposomes in the food industry, such as high cost and poor stability.

Impact of Delivery System Type on Curcumin Bioaccessibility: Comparison of Curcumin-Loaded Nanoemulsions with Commercial Curcumin Supplements.

In this study, nanoemulsion-based delivery systems fabricated using three different methods were compared with three commercially available curcumin supplements. Powdered curcumin was dispersed into the oil-in-water nanoemulsions using three methods: the conventional oil-loading method, the heat-driven method, and the pH-driven method. The conventional method involved dissolving powdered curcumin in the oil phase (60 °C, 2 h) and then forming a nanoemulsion. The heat-driven method involved forming a nanoemulsion and then adding powdered curcumin and incubating at an elevated temperature (100 °C, 15 min). The pH-driven method involved dissolving curcumin in an alkaline solution (pH 12.5) and then adding this solution to an acidified nanoemulsion (pH 6.0). The three commercial curcumin products were capsules or tablets purchased from an online supplier: Nature Made, Full Spectrum, and CurcuWin. Initially, the encapsulation efficiency of the curcumin in the three nanoemulsions was determined and decreased in the following order: pH-driven (93%) > heat-driven (76%) > conventional (56%) method. The different curcumin formulations were then subjected to a simulated gastrointestinal tract (GIT) model consisting of mouth, stomach, and small intestine phases. All three nanoemulsions had fairly similar curcumin bioaccessibility values (74-79%) but the absolute amount of curcumin in the mixed micelle phase was highest for the pH-driven method. A comparison of these nanoemulsions and commercial products indicated that the curcumin concentration in the mixed micelles decreased in the following order: CurcuWin ≈ pH-driven method > heat-driven method > conventional method ≫ Full spectrum > Nature Made. This study provides valuable information about the impact of the delivery system type on curcumin bioavailability. It suggests that encapsulating curcumin within small lipid particles may be advantageous for improving its absorption form the GIT.