Nutraceutically-enhanced oral delivery of vitamin D3 via Bio-SNEDDS: Demonstrating in vivo superiority over pediatric formulations.

BACKGROUND: Vitamin D3 (VD3) deficiency among children in Saudi Arabia remains a pressing concern due to its poor bioavailability and the limitations of current pediatric formulations. To address this challenge, we developed a groundbreaking pediatric self-nanoemulsifying drug delivery system (Bio-SNEDDS) for VD3, fortified with black seed oil and moringa seed oil for dual therapeutic benefits. Through meticulous formulation optimization using ternary phase diagrams and comprehensive testing, our Bio-SNEDDS demonstrated exceptional performance. METHODS: Bio-SNEDDS were manufactured by incorporating Black seed oil and moringa seed oil as bioactive nutraceutical excipients along with various cosurfactant and surfactants. Bio-SNEDDS were systematically optimized through ternary phase diagrams, visual tests, droplet size analysis, drug solubilization studies, dispersion assessments, and pharmacokinetic testing in rats compared to Vi-De 3®. RESULTS: Pseudoternary phase diagrams identified oil blends producing large nanoemulsion regions optimal for SNEDDS formation. The optimized F1 Bio-SNEDDS showed a mean droplet diameter of 33.7 nm, solubilized 154.46 mg/g VD3 with no metabolite formation, and maintained >88% VD3 in solution during 24 h dispersion testing. Notably, in vivo pharmacokinetic evaluation at a high VD3 dose demonstrated an approximately two-fold greater relative bioavailability over Vi-De 3®, validating the superb oral delivery performance of Bio-SNEDDS even under challenging high-dose conditions. CONCLUSIONS: The Bio-SNEDDS provides an effective VD3 delivery strategy with established in vivo superiority over marketed products, along with offering additional health benefits from the natural oils.

Novel Carbon Dots Derived from Moutan Cortex Significantly Improve the Solubility and Bioavailability of Mangiferin.

Background: Mangiferin (MA), a bioactive C-glucosyl xanthone with a wide range of interesting therapeutic properties, has recently attracted considerable attention. However, its application in biomedicine is limited by poor solubility and bioavailability. Carbon dots (CDs), novel nanomaterials, have immense promise as carriers for improving the biopharmaceutical properties of active components because of their outstanding characteristics. Methods: In this study, a novel water-soluble carbon dot (MC-CDs) was prepared for the first time from an aqueous extract of Moutan Cortex Carbonisata, and characterized by various spectroscopies, zeta potential and high-resolution transmission electron microscopy (HRTEM). The toxicity effect was investigated using the CCK-8 assay in vitro. In addition, the potential of MC-CDs as carriers for improving the pharmacokinetic parameters was evaluated in vivo. Results: The results indicated that MC-CDs with a uniform spherical particle size of 1-5 nm were successfully prepared, which significantly increased the solubility of MA in water. The MC-CDs exhibited low toxicity in HT-22 cells. Most importantly, the MC-CDs effectively affected the pharmacokinetic parameters of MA in normal rats. UPLC-MS analysis indicated that the area under the maximum blood concentration of MA from mangiferin-MC-CDs (MA-MC-CDs) was 1.6-fold higher than that from the MA suspension liquid (MA control) after oral administration at a dose of 20 mg/kg. Conclusion: Moutan Cortex-derived novel CDs exhibited superior performance in improving the solubility and bioavailability of MA. This study not only opens new possibilities for the future clinical application of MA but also provides evidence for the development of green biological carbon dots as a drug delivery system to improve the biopharmaceutical properties of insoluble drugs.

Natural Amino Acid-Bearing Carbamate Prodrugs of Daidzein Increase Water Solubility and Improve Phase II Metabolic Stability for Enhanced Oral Bioavailability.

Daidzein (DAN) is an isoflavone, and it is often found in its natural form in soybean and food supplements. DAN has poor bioavailability owing to its extremely low water solubility and first-pass metabolism. Herein, we hypothesized that a bioactivatable natural amino acid-bearing carbamate prodrug strategy could increase the water solubility and metabolic stability of DAN. To test our hypothesis, nine amino acid prodrugs of DAN were designed and synthesized. Compared with DAN, the optimal prodrug (daidzein-4'-O-CO-N-isoleucine, D-4'-I) demonstrated enhanced water solubility and improved phase II metabolic stability and activation to DAN in plasma. In addition, unlike the passive transport of DAN, D-4'-I maintained high permeability via organic anion-transporting polypeptide 2B1 (OATP2B1)-mediated transport. Importantly, D-4'-I increased the oral bioavailability by 15.5-fold, reduced the gender difference, and extended the linear absorption capacity in the pharmacokinetics of DAN in rats. Furthermore, D-4'-I exhibited dose-dependent protection against liver injury. Thus, the natural amino acid-bearing carbamate prodrug strategy shows potential in increasing water solubility and improving phase II metabolic stability to enhance the oral bioavailability of DAN.

The bioaccessibility and tolerability of marine-derived sources of magnesium and calcium.

It is generally accepted that mineral deficiencies, including magnesium and calcium, are widespread globally. Dietary supplementation may be an effective approach to combat such deficiencies. However, challenges associated with limited mineral solubility in the digestive system can impede effective dissolution and hinder absorption, leading to deficiency, and undesirable gastrointestinal disturbances including diarrhoea. Seawater is considered to be a rich source of bioactive magnesium, calcium, and 72 other trace minerals. In this study, we examine two different marine-derived multimineral products as potential dietary supplements. Aquamin-Mg, sourced from seawater is rich in magnesium (12%), and Aquamin F, a seaweed-derived multimineral is rich in calcium (32%). Both products also contain a diverse array of over 72 minerals, characteristic of their oceanic origin. Our study comprises two experiments. The first experiment evaluates and compares the solubility of Aquamin-Mg, commercially available magnesium bisglycinate, and Pure Magnesium Bisglycinate (PrizMAG) during in vitro digestion using the INFOGEST method. Results demonstrate that Aquamin-Mg exhibits superior solubility than the other magnesium sources during the gastric and intestinal phases, particularly when administered alongside food materials. The second experiment is a randomized, double-blind, placebo-controlled study in a small cohort of healthy older aged adults to assess the tolerability of a combined Aquamin-Mg/Aquamin-F supplement over a 12-week period. The findings indicate that this combination supplement is well-tolerated, with no significant adverse events reported, emphasizing its potential as a means of addressing mineral deficiencies.

Development of a self-microemulsifying drug delivery system to deliver delamanid via a pressurized metered dose inhaler for treatment of multi-drug resistant pulmonary tuberculosis.

Tuberculosis (TB) is a serious health issue that contributes to millions of deaths throughout the world and increases the threat of serious pulmonary infections in patients with respiratory illness. Delamanid is a novel drug approved in 2014 to deal with multi-drug resistant TB (MDR-TB). Despite its high efficiency in TB treatment, delamanid poses delivery challenges due to poor water solubility leading to inadequate absorption upon oral administration. This study involves the development of novel formulation-based pressurized metered dose inhalers (pMDIs) containing self-microemulsifying mixtures of delamanid for efficient delivery to the lungs. To identify the appropriate self-microemulsifying formulations, ternary diagrams were plotted using different combinations of surfactant to co-surfactant ratios (1:1, 2:1, and 3:1). The combinations used Cremophor RH40, Poly Ethylene Glycol 400 (PEG 400), and peppermint oil, and those that showed the maximum microemulsion region and rapid and stable emulsification were selected for further characterization. The diluted self-microemulsifying mixtures underwent evaluation of dose uniformity, droplet size, zeta potential, and transmission electron microscopy. The selected formulations exhibited uniform delivery of the dose throughout the canister life, along with droplet sizes and zeta potentials that ranged from 24.74 to 88.99 nm and - 19.27 to - 10.00 mV, respectively. The aerosol performance of each self-microemulsifying drug delivery system (SMEDDS)-pMDI was assessed using the Next Generation Impactor, which indicated their capability to deliver the drug to the deeper areas of the lungs. In vitro cytotoxicity testing on A549 and NCI-H358 cells revealed no significant signs of toxicity up to a concentration of 1.56 µg/mL. The antimycobacterial activity of the formulations was evaluated against Mycobacterium bovis using flow cytometry analysis, which showed complete inhibition by day 5 with a minimum bactericidal concentration of 0.313 µg/mL. Moreover, the cellular uptake studies showed efficient delivery of the formulations inside macrophage cells, which indicated the potential for intracellular antimycobacterial activity. These findings demonstrated the potential of the Delamanid-SMEDDS-pMDI for efficient pulmonary delivery of delamanid to improve its effectiveness in the treatment of multi-drug resistant pulmonary TB.

Sustained release of Zn from zinc sulfide nanoparticles (ZnS NPs) amplified the bioaccessibility of Zn in soil: Adsorption dynamics and dissolution kinetics.

Controlled-release micronutrient supplementation to provide better bioavailable zinc (Zn) under alkaline soil conditions is a concept of commercial pertinence for sustainable agriculture. High pH stable nano-scaled ZnS is the material under study in the present investigation where the adsorption dynamics and dissolution kinetics of sono-chemically synthesized zinc sulfide nanoparticles (ZnS NPs) were evaluated in comparison to ZnSO4 in Lufa 2.2 soil for supplementation of Zn. The mechanism of adsorption of ZnS NPs and ZnSO4 onto Lufa 2.2 soil was well explained by fitting into the Freundlich adsorption model and pseudo-second order equation. ZnS NPs reflected the stronger ability to get adsorbed on the Lufa 2.2 soil as compared to metal ions, due to higher surface reactivity of NPs and higher Kf value (0.557) than ZnSO4 (0.463). Time relevant enhancement in extractability of Zn from ZnS NPs amended soil and diminution in extractability of Zn from ZnSO4 spiked soil was observed in bioavailability studies. The increased labile pool of Zn from ZnS NPs amended soil over time was due to their slow dissolution in soil and could be adjusted to consider as "sustained released ZnS NPs". Dissolution of ZnS nanoparticles (NPs) in Lufa 2.2 soil adhered to the first-order extraction model, exhibiting extended half-lives of 27.72 days (low dose) and 28.87 days (high dose). This supported prolonged stability, increased reactivity, and reduced ecological risk compared to conventional Zn salt fertilizers, promoting enhanced crop productivity.

Methods for testing short- and long-term phosphorus fertilizing efficiency of products with varying solubility.

Phosphorus (P) recovery from nutrient-rich side streams (NRSS) and derived products is crucial to ensure sustainable food production in the future and to enhance the circular economy, but the agronomic efficiency of these products needs to be validated to reach these targets. In this study, we used a Hedley fractionation scheme and the diffusive gradient in thin film (DGT) method to determine P availability in 83 NRSS and derived products originating from Finland, Sweden, and Germany. Furthermore, two independent short- and long-term growth experiments with barley (Hordeum vulgare L.) and ryegrass (Lolium perenne L.), respectively, were conducted to evaluate P availability in 15 selected NRSS. In addition to the DGT soil test, different fertilizer extractants, 2 % formic acid (FA), 2 % citric acid, and neutral ammonium citrate, were tested for predicting P availability in growth experiments. Livestock manures and slurries were found to contain a notable portion of labile P and were comparable to superphosphate (SP). Despite the low shares of labile P in struvite (7.2 %) and AshDec® (1.3 %), they exhibited P availability comparable to SP fertilizer, as indicated by DGT (99 % and 238 % of SP equivalence, respectively). This suggests that factors other than solubility influenced P availability in these side streams. The DGT method as a promising soil test predicted both short- and long-term P availability better than the selected conventional chemical extraction methods did. The 2 % FA extract exhibited the poorest performance, overestimating P availability in some nutrient sources while underestimating others in long-term. These findings enhance our understanding of P availability in potential raw materials for fertilizers, facilitating more effective P management strategies in the circular economy.

The effect of naringenin-phospholipid complex on thermal oxidative stability of soybean oil under heating condition.

Naringenin (NGE), a typical flavanone abundant in citrus fruits, exhibits remarkable antioxidant activities. However, its low solubility in oil restricts its widespread use in inhibiting lipid oxidation. In this study, we present a novel and effective approach to address this limitation by developing a naringenin-phospholipid complex (NGE-PC COM). Comprehensive analytical techniques including Fourier transform infrared (FTIR), differential scanning calorimetry (DSC), and X-ray diffraction (XRD) were employed to confirm the formation of the NGE-PC COM and elucidate the interaction mechanism between NGE and phospholipids molecules. Notably, the oil-solubility of NGE was significantly enhanced by approximately 2700-fold when formulated as a phospholipid complex in soybean oil. The improved oil-solubility of NGE-PC COM enabled effective inhibition of oil thermal oxidation under high temperature conditions. Generally, this investigation proposed a novel and promising strategy for employing flavanones with strong antioxidant activities to enhance the thermal oxidative stability of edible oil during heating processes.

Green Tea Catechins Decrease Solubility of Raloxifene In Vitro and Its Systemic Exposure in Mice.

PURPOSE: Green tea is a widely consumed beverage. A recent clinical study reported green tea decreased systemic exposure of raloxifene and its glucuronide metabolites by 34-43%. However, the underlying mechanism(s) remains unknown. This study investigated a change in raloxifene's solubility as the responsible mechanism. METHODS: The effects of green tea extract, (-)-epigallocatechin gallate (EGCG), and (-)-epigallocatechin (EGC) on raloxifene's solubility were assessed in fasted state simulated intestinal fluids (FaSSIF) and fed state simulated intestinal fluids (FeSSIF). EGCG and EGC represent green tea's main bioactive constituents, flavan-3-gallate and flavan-3-ol catechins respectively, and the tested concentrations (mM) match the µg/mg of each compound in the extract. Our mouse study (n = 5/time point) evaluated the effect of green tea extract and EGCG on the systemic exposure of raloxifene. RESULTS: EGCG (1 mM) and EGC (1.27 mM) decreased raloxifene's solubility in FaSSIF by 78% and 13%, respectively. Micelle size in FaSSIF increased with increasing EGCG concentrations (> 1000% at 1 mM), whereas EGC (1.27 mM) did not change micelle size. We observed 3.4-fold higher raloxifene solubility in FeSSIF compared to FaSSIF, and neither green tea extract nor EGCG significantly affected raloxifene solubility or micelle size in FeSSIF. The mice study showed that green tea extract significantly decreased raloxifene Cmax by 44%, whereas EGCG had no effect. Green tea extract and EGCG did not affect the AUC0-24 h of raloxifene or the metabolite-to-parent AUC ratio. CONCLUSIONS: This study demonstrated flavan-3-gallate catechins may decrease solubility of poorly water-soluble drugs such as raloxifene, particularly in the fasted state.

Effect of high moisture extrusion on the structure and physicochemical properties of Tartary buckwheat protein and its in vitro digestion.

Tartary buckwheat is rich in nutrients and its protein supports numerous biological functions. However, the digestibility of Tartary buckwheat protein (TBP) poses a significant limitation owing to its inherent structure. This study aimed to assess the impact of high moisture extrusion (HME, 60 % moisture content) on the structural and physicochemical attributes, as well as the in vitro digestibility of TBP. Our results indicated that TBP exhibited unfolded and amorphous microstructures after HME. The protein molecular weight of TBP decreased after HME, and a greater degradation was observed at 70 °C than 100 °C. In particular, HME at 70 °C caused an almost complete disappearance of bands near 35 kDa compared with HME at 100 °C. In addition, compared with native TBP (NTBP, 44.53 µmol/g protein), TBP subjected to HME at 70 °C showed a lower disulfide bond (SS) content (42.67 µmol/g protein), whereas TBP subjected to HME at 100 °C demonstrated a higher SS content (45.70 µmol/g protein). These changes endowed TBP with good solubility (from 55.96 % to 83.31 % at pH 7), foaming ability (20.00 %-28.57 %), and surface hydrophobicity (8.34-23.07). Furthermore, the emulsifying activity (EA) and in vitro digestibility are closely related to SS content. Notably, extruded TBP (ETBP) obtained at 70 °C exhibited higher EA and digestibility than NTBP, whereas ETBP obtained at 100 °C showed the opposite trend. Consequently, HME (especially at 70 °C) demonstrated significant potential as a processing technique for improving the functional and digestive properties of TBP.

Formulation and optimization of a single-layer coat for targeting budesonide pellets to the descending Colon.

The current budesonide formulations are inadequate for addressing left-sided colitis, and patients might hesitate to use an enema for a prolonged time. This study focuses on developing a single-layer coating for budesonide pellets targeting the descending colon. Pellets containing budesonide (1.5%w/w), PVP K30 (5%w/w), lactose monohydrate (25%w/w) and Avicel pH 102 (68.5%w/w) were prepared using extrusion spheronization technique. Coating formulations were designed using response surface methodology with pH and time-dependent Eudragits. Dissolution tests were conducted at different pH levels (1.2, 6.5, 6.8, and 7.2). Optimal coating formulation, considering coating level and the Eudragit (S + L) ratio to the total coating weight, was determined. Budesonide pellets were coated with the optimized composition and subjected to continuous dissolution testing simulating the gastrointestinal tract. The coating, with 48% S, 12% L, and 40% RS at a 10% coating level, demonstrated superior budesonide delivery to the descending colon. Coated pellets had a spherical shape with a uniform 30 µm thickness coating, exhibiting pH and time-dependent release. Notably, zero-order release kinetics was observed for the last 9 h in colonic conditions. The study suggests that an optimized single-layer coating, incorporating pH and time-dependent polymers, holds promise for consistently delivering budesonide to the descending colon.

Water solubility differentiates the impact of tea polyphenols and rutin on the postprandial glycemic response to cooked maize starch.

Postprandial hyperglycemia is an independent risk factor for cardiovascular diseases, and the impact of tea polyphenols (TP) and rutin, representative phenolic compounds with different water solubilities, on the postprandial glycemic response to cooked normal corn starch (CCS) was investigated. Comparatively, TP (DPPH50 = 0.12 mmol L-1) are more potent than rutin (DPPH50 = 0.50 mmol L-1) in scavenging the free radicals of DPPH, but both TP and rutin inhibited the activity of porcine pancreatic α-amylase (PPA), the major enzyme in starch digestion, with an IC50 of 4.09 mmol L-1 and 2.71 mmol L-1, respectively. However, an in vivo study showed that a significant reduction in postprandial blood glucose was only observed in the presence of rutin, and TP had no effect on the glycemic response to CCS. To find out the underlying mechanism, fluorescence spectroscopy and molecular docking were carried out and they showed that, compared to TP, rutin bound to the active site of PPA with higher affinity and a lower free energy (ΔG) driven by hydrogen bonds and π-stacking, and rutin also greatly increased the viscosity of starch. Collectively, water-soluble TP have a higher antioxidant property and a lower potency to inhibit PPA compared to water-insoluble rutin, and the weaker interaction between TP and PPA, and starch as well might synergistically contribute to TP's ineffectiveness in lowering the postprandial glycemic response, and water solubility linking the molecular structures and functions of phenolic compounds might be the fundamental basis for the observed difference in their biological functions, and water solubility can also be used to enrich specific phenolic compounds for desired functions.

Formulation Studies with Cyclodextrins for Novel Selenium NSAID Derivatives.

Commercial cyclodextrins (CDs) are commonly used to form inclusion complexes (ICs) with different molecules in order to enhance their water solubility, stability, and bioavailability. Nowadays, there is strong, convincing evidence of the anticancer effect of selenium (Se)-containing compounds. However, pharmaceutical limitations, such as an unpleasant taste or poor aqueous solubility, impede their further evaluation and clinical use. In this work, we study the enhancement of solubility with CD complexes for a set of different nonsteroidal anti-inflammatory drug (NSAID) derivatives with Se as selenoester or diacyl diselenide chemical forms, with demonstrated antitumoral activity. The CD complexes were analyzed via nuclear magnetic resonance (NMR) spectroscopic techniques. In order to obtain additional data that could help explain the experimental results obtained, 3D models of the theoretical CD-compound complexes were constructed using molecular modeling techniques. Among all the compounds, I.3e and II.5 showed a remarkable increase in their water solubility, which could be ascribed to the formation of the most stable interactions with the CDs used, in agreement with the in silico studies performed. Thus, the preliminary results obtained in this work led us to confirm the selection of ß and γ-CD as the most suitable for overcoming the pharmaceutical drawbacks of these Se derivatives.

Curcumin- ß-Cyclodextrin Molecular Inclusion Complex: A Water-Soluble Complex in Fast-dissolving Tablets for the Treatment ofNeurodegenerative Disorders.

BACKGROUND: Orally disintegrating tablets (ODTs) have become an excellent choice for delivering drugs as their palatability is greatly improved. In this work, ß-cyclodextrin has been used to improve the solubility of curcumin by encapsulating it into the hydrophobic cavity for the treatment of neurodegenerative disorders. OBJECTIVES: The current study aimed to present the design, formulation, and optimisation of fastdissolving oral tablets of curcumin- ß-cyclodextrin molecular inclusion complex using a 32-factorial design. METHODS: The drug-excipient compatibility was studied by FTIR spectroscopy. The inclusion complex of curcumin-ß-cyclodextrin was prepared using solvent casting and confirmed using XRD studies. Powder blends were evaluated for flow properties. Tablets prepared by direct compression were evaluated for post-compression parameters. Further, the effect of formulation variables, such as sodium starch glycolate (X1) and Neusilin® ULF2 (X2), on various responses, including disintegration time and dissolution at 2 hours, was studied using statistical models. RESULTS: Post-compression parameters, i.e., hardness (4.4-5 kg/cm2), thickness (3.82-3.93 mm), weight variation (±7.5%), friability (< 1%), wetting time (51-85 seconds) and drug content (96.28- 99.32%) were all found to be within the permissible limits and the disintegration time of tablets with super-disintegrants ranged between 45-58 seconds. The in-vitro dissolution profile of tablets showed that higher SSG and Neuslin® ULF2 levels promoted drug release. For statistical analysis, the 2FI model was chosen. Optimised variables for formulation have been determined and validated with the experimental findings based on the significant desirability factor. CONCLUSION: The current study reveals the validated curcumin-ß-cyclodextrin inclusion complex fastdissolving tablets with SSG and Neusilin® ULF2 to be an ideal choice for effectively treating neurodegenerative disorders.

[Application of Hydrogenated Soya Lecithin in Solid Dispersion and Oily Gel, and the Study of Skin-Applied Formulations].

I have been studying the improvement of drug solubility using solid dispersion and skin-applied formulations. When preparing solid dispersions using phosphatidylcoline (PC) as a carrier, drug with hydrogen-donating groups interacts with PC to produce amorphous solid dispersions with high drug content; this overcomes improves drug absorption. The drug was solubilized and supersaturated in the oil-based gel formed with hyadrogenated lecithin; this facilitates drug permeation through the skin. The promoting effect differs with the nature of the oil used because of the skin penetration of the oil itself and the accompanying increase in drug solubility and diffusion coefficient in the skin. At actual application volumes of 10 µL/cm2 or less, the skin penetration of poorly-absorbable drugs depends on the molecular weight and surface tension of the oil. The penetration of the oil vehicle into the upper stratum corneum influences the reach of the drug into the stratum corneum; a high drug concentration near the 7th layer of the stratum corneum promotes migration through the skin by increasing the linear concentration gradient in deeper layers. In addition, we performed a risk assessment, in collaboration with toxicologists, for dermal safety that included the toxicity potential of substances and the parts related to skin transfer.

Investigating the prilling/vibration technique to produce gastric-directed drug delivery systems for misoprostol.

Prilling/vibration technique to produce oral microcapsules was explored to achieve local delivery of misoprostol (MIS), a prostaglandin E1 analogue indicated for the treatment of gastric-duodenal ulcers, at the gastric mucosa. To improve MIS chemical stability and reduce its associated systemic side effects, drug delivery systems were designed and developed as microcapsules consisting of a core of sunflower oil and MIS (Fs6 and Fs14) or a MIS complex with hydroxypropyl-beta-cyclodextrin (HP-ß-CD) (Fs18), confirmed by specific studies, and a polymeric shell. The produced microcapsules showed high encapsulation efficiencies for those with MIS solubilized in sunflower oil (>59.86 %) and for the microcapsules with MIS/HP-ß-CD (97.61 %). To demonstrate the ability of these systems to deliver MIS into the stomach, swelling and drug release experiments were also conducted in simulated gastric fluid. Among the three formulations, FS18 showed gastric release within 30 min and was the most advantageous formulation because the presence of the MIS/HP-ß-CD inclusion complex ensured a greater ability to stabilise MIS in the simulated gastric environment. In addition, these new systems have a small size (<540 µm), and good flow properties and the dose of the drug could be easily adapted using different amounts of microcapsules (flexibility), making them a passepartout for different age population groups.

Ultrasound-assisted macroporous resin treatment improves the color and functional properties of sunflower meal protein.

Sunflower meal protein (SMP) has been considered as a high-quality source of plant protein. However, because the chlorogenic acid (CA) contained in sunflower seed meal was prone to oxidation reactions under traditional alkali extraction conditions, the extracted protein has a dark color and some poor functional properties. To this end, this study used ultrasound-assisted macroporous resin treatment to extract SMP. The improvement effects and potential mechanisms of ultrasonic-assisted macroporous resin treatment with different powers (100, 300, and 500 W) on the color and functional properties of SMP were studied. The results showed that compared with untreated sunflower meal protein (USMP), the lightness value (L*), solubility, emulsification, and gel elasticity were significantly enhanced when treated with 100 W and 300 W ultrasonic-assisted macroporous resin. However, when the ultrasonic power was increased to 500 W, the L* value, solubility, emulsification, and gel elasticity decreased instead, indicating that lower power (100 W and 300 W) ultrasonic-assisted macroporous resin treatment significantly improved the color and functional properties of SMP. Further research found that ultrasound-assisted macroporous resin treatment changed the secondary and tertiary structures of SMP, transformed ß-sheet into α-helix and ß-turn through rearrangement, and significantly improved surface hydrophobicity. It shows that ultrasonic-assisted macroporous resin treatment expands the SMP structure and exposes hydrophobic groups, thereby improving the color and functional properties of SMP. This study provides a potential strategy for extracting SMP with light color and good functional properties. It also provides a theoretical basis for the wide application of SMP in food processing.

Enhancing the therapeutic potential of curcumin: a novel nanoformulation for targeted anticancer therapy to colorectal cancer with reduced miR20a and miR21 expression.

Curcumin (Cur) possesses remarkable pharmacological properties, including cardioprotective, neuroprotective, antimicrobial, and anticancer activities. However, the utilization of Cur in pharmaceuticals faces constraints owing to its inadequate water solubility and limited bioavailability. To overcome these hurdles, there has been notable focus on exploring innovative formulations, with nanobiotechnology emerging as a promising avenue to enhance the therapeutic effectiveness of these complex compounds. We report a novel safe, effective method for improving the incorporation of anticancer curcumin to induce apoptosis by reducing the expression levels of miR20a and miR21. The established method features three aspects that, to our knowledge, have not been formally verified: (1) use of a novel formula to incorporate curcumin, (2) use of all biocompatible biodegradable materials to produce this formula without leaving harmful residues, and (3) an incorporation process at temperatures of approximately 50 °C. The formula was prepared from lecithin (LE), and chitosan (CH) with an eco-friendly emulsifying agent and olive oil as the curcumin solvent. The formula was converted to nanoscale through ultrasonication and probe sonication at a frequency of 20 kHz. Transmission electron microscopy showed that the nano formula was spherical in shape with sizes ranging between 49.7 nm in diameter and negative zeta potentials ranging from 28 to 34 mV. Primers miR20a and miR21 were designed for molecular studies. Nearly complete curcumin with an encapsulation efficiency of 91.1% was established using a straight-line equation. The nano formula incorporated with curcumin was used to prepare formulations that exhibited anticancer activities. The apoptosis pathway in cancer cells was activated by the minimum inhibitory concentration of the nano formula. These findings suggest the potential of this nanoformulation as an effective and selective cancer treatment that does not affect the normal cells.

Riboflavin Crystals with Extremely High Water Solubility.

New insights into the unique biochemical properties of riboflavin (Rf), also known as vitamin B2, are leading to the development of its use not only as a vitamin supplement but also as a potential anti-inflammatory, immunomodulatory, antioxidant, anticancer, and antiviral agent, where it may play a role as an inhibitor of viral proteinases. At the same time, the comparison of the pharmacoactivity of Rf with its known metabolites, namely, flavin mononucleotide (FMN) and flavin adenine dinucleotide (FAD), is very complicated due to its poor water solubility: 0.1-0.3 g/L versus 67 g/L for FMN and 50 g/L for FAD, which is the limiting factor for its administration in clinical practice. In this study, we report the recrystallization procedure of the type A Rf crystals into the slightly hydrophobic type B/C and a new hydrophilic crystal form that has been termed the P type. Our method of Rf crystal modification based on recrystallization from dilute alkaline solution provides an unprecedented extremely high water solubility of Rf, reaching 23.5 g/L. A comprehensive study of the physicochemical properties of type P riboflavin showed increased photodynamic therapeutic activity compared to the known types A and B/C against clinical isolates of Staphylococcus aureus, Pseudomonas aeruginosa, Escherichia coli, and Salmonella typhimurium. Importantly, our work not only demonstrates a simple and inexpensive method for the synthesis of riboflavin with high solubility, which should lead to increased bioactivity, but also opens up opportunities for improving both known and new therapeutic applications of vitamin B2.

Preparation of astaxanthin-loaded composite micelles with coaxial electrospray technology for enhanced oral bioavailability and improved antioxidation capability.

BACKGROUND: Astaxanthin (AST) is approved by the US Food and Drug Administration (FDA) as a safe dietary supplement for humans. As a potent lipid-soluble keto-carotenoid, it is widely used in food, cosmetics, and the pharmaceutical industry. However, its low solubility limits its powerful biological activity and its application in these fields. This study aims to develop a delivery system to address the low solubility and bioavailability of AST and to enhance its antioxidant capacity. RESULTS: Astaxanthin-loaded composite micelles were successfully prepared via coaxial electrospray technology. Astaxanthin existed in the amorphous state in the electro-sprayed formulation with an approximate particle size of 186.28 nm and with a polydispersity index of 0.243. In this delivery system, Soluplus and copovidone (PVPVA 64) were the main polymeric matrix for AST, which then released the drug upon contact with aqueous media, resulting in an overall increase in drug solubility and a release rate of 94.08%. Meanwhile, lecithin, and Polyethylene glycol-grafted Chitosan (PEG-g-CS) could support the absorption of AST in the gastrointestinal tract, assisting transmembrane transport. The relative bioavailability reached about 308.33% and the reactive oxygen species (ROS) scavenging efficiency of the formulation was 44.10%, which was 1.57 times higher than that of free astaxanthin (28.10%) when both were at the same concentration level based on astaxanthin. CONCLUSION: Coaxial electrospray could be applied to prepare a composite micelles system for the delivery of poorly water-soluble active ingredients in functional food, cosmetics, and medicine. © 2023 Society of Chemical Industry.