Folic Acid Solution Research Articles

The interaction mechanism between zein and folic acid in alkaline aqueous solutions: an experimental and molecular simulation study

Abstract Objectives Folic acid is a vitamin that is not highly soluble in water and is sensitive to the environment. Therefore, it is important to find suitable carriers. This study aimed to exemplify the interaction of folic acid with zein in alkaline aqueous solutions and shed light on how zein can be used as a carrier for folic acid. Materials and Methods Zein and folic acid were separately dissolved in NaOH solutions with a PH of 11.5. Zein solution and folic acid solution were combined in specific ratios. Various methods including multi-spectroscopy, dynamic light scattering, and electron microscopy combining with molecular dynamics simulations were used to study the interaction mechanism between zein and folic acid in alkaline aqueous solutions. Results Fluorescence spectroscopy showed that the quenching of zein by folic acid was mainly static, and the main driving force behind this interaction was van der Waals forces and hydrogen bonds. The formation of zein–folic acid complexes was confirmed by ultraviolet–visible spectroscopy, Fourier transform infrared spectroscopy, and circular dichroism spectroscopy. The results also showed that the structure of zein changed when it interacted with folic acid. Dynamic light scattering analysis revealed that the addition of folic acid caused proteins to aggregate. The aggregates of the complexes had an irregular shape and were large, as observed by scanning electron microscopy and transmission electron microscopy. Molecular simulation was used to further investigate the interaction mechanisms. According to these findings, the folic acid molecule interacted with zein in a shallow recess near the protein surface. The dominant forces at play in the zein–folic acid interaction were van der Waals forces and electrostatic forces, including hydrogen bonding. Conclusion The zein alkali-soluble system is very suitable for folic acid delivery.

Physicochemical Analysis of Zinc Oxide Nanodispersion in Folic Acid Solution at T = 303.15 K

Physicochemical Analysis of Zinc Oxide Nanodispersion in Folic Acid Solution at T = 303.15 K

Folic Acid Ionic-Liquids-Based Separation: Extraction and Modelling.

Folic acid (vitamin B9) is an essential micronutrient for human health. It can be obtained using different biological pathways as a competitive option for chemical synthesis, but the price of its separation is the key obstacle preventing the implementation of biological methods on a broad scale. Published studies have confirmed that ionic liquids can be used to separate organic compounds. In this article, we investigated folic acid separation by analyzing 5 ionic liquids (CYPHOS IL103, CYPHOS IL104, [HMIM][PF6], [BMIM][PF6], [OMIM][PF6]) and 3 organic solvents (heptane, chloroform, and octanol) as the extraction medium. The best obtained results indicated that ionic liquids are potentially valuable for the recovery of vitamin B9 from diluted aqueous solutions as fermentation broths; the efficiency of the process reached 99.56% for 120 g/L CYPHOS IL103 dissolved in heptane and pH 4 of the aqueous folic acid solution. Artificial Neural Networks (ANNs) were combined with Grey Wolf Optimizer (GWO) for modelling the process, considering its characteristics.

Spectrophotometric determination of Folic acid (B9) by oxidative Coupling Reaction with 4-nitro-aniline

Development of an easy, inexpensive, fast and selective spectrophotometric method for the determination of Folic Acid (FA) by its reaction with 4-nitro aniline reagent, with good sensitivity, as an oxidative coupling method in the presence of Potassium permanganate solution, and it was found that the concentrations that were agreement with Beer-Lambert’s law at the wavelength of 374 nm ranged between 1- 21 µg/ml of folic acid solution, and a deviation from Beer’s law occurs at a concentration higher than 21 µg/mL, gave a linear coefficient and correlation coefficient its value is 0.9994, 0.9996, respectively, While the value of the molar absorption coefficient 12138.5 L/mol.cm and Sandel's sensitivity 0.0363 gm/cm2 with the limits of qualitative and quantitative detection 0.103 and 0.363 μg / ml-1, respectively. The proposed method was successfully applied for the determination of folic acid in its pharmaceutical preparations, from Erbil Company – Iraq. Trade name (folic acide).

Folic acid delays postharvest quality deterioration of table grape by regulating cell wall metabolism-associated hub WRKY31 transcription factor

Grape (Vitis vinifera L.) berries are susceptible to quality deterioration after harvest. This study aimed to investigate the effect of folic acid (FA) treatment on the postharvest quality of table grape berries. Harvested ‘Kyoho’ (V. vinifera × V. labrusca L.) bunches were immersed in 1 mg L−1 FA solution for 15 min, then stored for sample collection and phenotype observation. Treatment with FA decreased the rates of berry abscission, water loss, and berry softening, reduced the accumulation of reactive oxygen species (ROS), and altered ROS metabolism-associated enzyme activities and gene expression levels. Transcriptome analysis revealed 507, 684, and 250 differentially expressed genes (DEGs) between FA-treated and non-treated berries at 3, 6, and 9 d after treatment, respectively. The DEGs were grouped into six modules according to a weighted correlation network analysis. A hub transcription factor, annotated as a WRKY transcription factor, was screened from the module associated with cell wall metabolism and identified as VvWRKY31. Transient transformation of grape berry slices revealed that overexpression of VvWRKY31 enhanced the relative expression level of VvRboh. The dual-luciferase assay showed that VvWRKY31 was capable of binding to VvRboh promoter. The present results provide insights into the potential molecular mechanism underlying FA-induced delay postharvest quality deterioration of grape berries. Specifically, FA inhibits expression of genes associated with ROS generation by reducing VvWRKY31 expression, thereby delaying quality deterioration induced by excessive accumulation of ROS. These results will be helpful in table grape breeding programs focused on delaying deterioration in postharvest quality.

Highly Specific Silver Ion Detection by Fluorescent Carbon Quantum Dots

Nitrogen-doped carbon quantum dots are easily obtainable nanomaterials endowed with remarkable fluorescence properties for the detection of contaminations by heavy metals. In this report, we show that nanometric particles with high specificity for silver cations can be prepared by hydrothermal synthesis starting from citric and folic acid solutions. Solutions of these N-CQDs give a strong fluorescence emission in the violet region (385 nm) when excited at 330 nm, which can be quenched selectively by silver (I) cations at sub-nanomolar concentrations, while other cations do not give any effect. This remarkable feature was tentatively correlated with the stronger interactions between silver ion and small portions of the nanomaterial surface by comparing Ag+ and the isoelectronic Cd2+.

Development and validation of UV-spectrophotometric method for the determination of folic acid in bulk and tablet dosage forms

The purpose of this study was to create and verify a simple and accurate UV-Spectrophotometric technique for determining Folic acid in bulk and tablet dosage form. The approach was based on the measurement of folic acid solution absorbance at 255nm in 0.01M NaOH. In the concentration range of 10-50 g/ml, the constructed calibration curve was found to be linear (R2 = 0.9996). Limits of detection and quantification were 2.73 µg/ml, and 8.27 µg/ml, respectively. The precision of the developed method was confirmed by the obtained low RSD% values. Recoveries percentages were found 98.46%±1.42, 100.0%±0.20, 98.92%±1.12; n=3 for 50%, 100% and 150% levels, respectively indicating the method accuracy and freedom of interference from excipients. Folic acid content percent in the two analyzed brands were found to be equal 96.59%±0.005; n=3, and 97.28%±0.003; n=3 which complies with the official range (90-110%).

Folic acid alleviates lead acetate-mediated cardiotoxicity by down-regulating the expression levels of Nrf2, HO-1, GRP78, and CHOP proteins.

The purpose of this study was to explore the interventional effects of folic acid on the heart damage caused by lead acetate exposure. Twenty-four 60-day-old male Sprague-Dawley (SD) rats were randomly divided into 4 groups with 6 rats in each group. The control group (C group) was normal rats; the lead exposure group (L group) rats drank 0.2% lead acetate solution freely for 14days. The rats in the intervention group (T group) were given 0.2% lead acetate solution for 14days, respectively, and 0.4mg/kg BW folic acid solution was given to the rats by gavage on the 7th day of lead administration. The rats in the folic acid group (group E) were given 0.4mg/kg BW folic acid solution by gavage. To weigh rat body weight and heart weight, calculate heart index, and observe the expression level of nuclear factor erythroid 2-related factor 2(Nrf2), heme oxygenase 1(HO-1), glucose-regulated protein 78/binding immunoglobulin protein (GRP78), and C/EBP-homologous protein (CHOP) by immunofluorescence method. The results showed that compared with group C, serum lead levels in group L and T were significantly increased (P < 0.05); superoxide dismutase (SOD), glutathione (GSH), and glutathione peroxidase (GSH-PX) levels in group L were significantly decreased (P < 0.05), and malondialdehyde (MDA) content was significantly higher increased (P < 0.05), and the GSH-PX content in group T were significantly increased in group L (P < 0.05), and the MDA content in group T was significantly lower than that in group L (P < 0.05). Compared with group C, the expression of Nrf2, HO-1, GRP78, and CHOP in group L increased significantly, and the difference was statistically significant (P < 0.05). Compared with the L group, the expression of Nrf2, HO-1, GRP78, and CHOP in the T group was reduced. Therefore, folic acid has a certain protective effect on the oxidative damage of lead-exposed rat heart tissue. Lead exposure will increase ROS, NO, MDA, and other oxidizing substances and reduce the level of GSH, SOD, CAT, GPx, and other antioxidant factors, which will lead to cardiac hypertrophy, cardiac index increase, oxidative stress, Nrf2, and HO-1. The expression of stress-related proteins such as GRP78 and CHOP also increased, leading to cardiomyocyte apoptosis. After a folic acid intervention, these changes can be significantly reversed.

Quadruple fortification of salt for the delivery of iron, iodine, folic acid, and vitamin B12 to vulnerable populations.

A process for simultaneous delivery of iron, iodine, folic acid, and vitamin B12 through salt as a potential and holistic approach to ameliorate anaemia and reduce maternal and infant mortality is presented. Two approaches for adding folic acid and B12 to salt during double fortification with iron and iodine were investigated. Attempts to add both micronutrients through the iodine spray solution were unsuccessful. Hence, folic acid was added through a stabilized iodine solution, and B12 was added through the iron premix. Four approaches used to incorporate B12 into the iron premix were investigated: (1) co-extruding B12 with iron, (2) spraying B12 on the surface of the iron extrudate, (3) adding B12 to the colour masking agent, and (4) adding B12 to the outer coating. Of these approaches, coextrusion (1) was the best, based on the ease of production and stability of fortificants. The salt formulated with the solid iron-B12 premix and sprayed iodine and folic acid solution contained 1000 ppm iron, 50 ppm iodine, 25 ppm folic acid, and 0.25 ppm B12. Over 98% of B12, 93% folic acid, and 94% iodine were retained after 6-month storage in the best formulation. This technology can simultaneously deliver iron, iodine, folic acid, and vitamin B12 in a safe and stable salt enabling public health measures for improved health at a minimal additional cost.

Improved photostability of folic acid by the radical-scavenging effect of tannic acid

Folic acid (FA) is sensitive to ultraviolet (UV) light and decomposes into photoproducts with higher fluorescence quantum yield: 6-formylpterin (Fop) and p-aminobenzoylglutamic acid (PABA-Glu). Fop is subsequently oxidized into 6-carboxypterin (Cap). The increased fluorescence intensity of FA solution with increasing irradiation time proved the degradation. Addition of tannic acid (TA) at the TA/FA molar ratio of 0.025/1 could protect 99% FA compared to that no FA could be detected without addition of TA after 120 min of UV irradiation. The retention of FA without TA at pH 5–6 was below 0.4% and above 93% at pH 3–4, but the retention of FA with TA was over 97% for pH 3–6. Moreover, the retention of FA with TA in gummy was over 81% which was significantly higher than that of the one without TA. No covalent bonds were formed between TA and FA. Ethylenediaminetetraacetic acid could not protect FA against photodegradation. Ascorbic acid (Vc) could protect FA to the same extent as TA, but with more addition. It agreed with the results that the DPPH radical-scavenging effect of Vc is lower than TA. These results demonstrated that TA could improve the photostability of FA by the radical-scavenging effect.

Vitamin E-based Folic Acid Nanoemulsion: Formulation and Physical Evaluation for Oral Administration.

Background: Folic acid is essential in many metabolic processes and DNA synthesis. Nevertheless, folic acid is not stable, pH-sensitive, and deteriorated upon light exposure.Objective: This work was aimed to improve folic acid stability within vitamin E-based nanoemulsion.Methods: The nanoemulsion was prepared with self-nanoemulsification method by mixing vitamin E oil, Tween 20, and PEG 400. A pseudoternary phase diagram was constructed with aqueous titration to determine the optimum ratio for the mixture. The globule size, pH and entrapment efficiency were included in the nanoemulsion characterizations. In addition, the influence of centrifugation, storage, and pH on physical and chemical stabilities of folic acid nanoemulsion was evaluated.Results: Optimum formula was obtained from vitamin E, Tween 20, and PEG 400 with the ratio of 1:11:1, and the folic acid amount was 8 mg. The size of folic acid-loaded oil globule was 15.10 ± 1.51 nm, and the nanoemulsion pH was 6.24 ± 0.01. The nanoemulsion system was able to load the folic acid completely. Folic acid in nanoemulsion was stable after 14 days at room temperature, and it was more stable compared to folic acid in solution. In addition, the physical and chemical characteristics of folic acid in nanoemulsion was not affected by the simulated gastric condition.Conclusion: Hence, nanoemulsion is a promising strategy to enhance folic acid stability.

Folic acid and its metabolite codetermination for pharmacokinetics with circadian rhythms and evaluation of oral bioavailability.

Pharmacokinetics of vitamins is still a challenge. In this study, folic acid (FA) was used as a model drug and aimed at investigating a reliable method for its detailed pharmacokinetic evaluations. An high-performance liquid chromatography-tandem mass spectrometry method was developed and performed to determinate the FA and 5-methyltetrahydrofolic acid (5-methylTHF) simultaneously, which was applied to characterize the circadian rhythms as well as the pharmacokinetics of different preparations. The plasma concentration of 5-methylTHF in fasted state was twofold higher than that in fed state. The circadian rhythms were studied before the pharmacokinetics and revealed that free FA was almost undetected in blank plasma, while 5-methylTHF had a slight decrement at 12:00. Hence, the pharmacokinetics of FA was conducted and showed that the administration of FA solution resulted in enhancing bioavailability of 5-methylTHF comparing with FA raw material suspension, whereas the free FA level in plasma was similar. The mechanism could be that FA was rapidly metabolized to 5-methylTHF in intestinal epithelial cell after absorption, which revealed that intestinal metabolism would affect its bioavailability. A suitable method was established considering the baseline level, circadian rhythms and intestinal metabolism to investigate the pharmacokinetics of FA for guiding the further research of vitamins.

Physical Absorption of Folic Acid and Chitosan on Dihydroartemisinin-Loaded Poly-Lactic-Co-Glycolic Acid Nanoparticles via Electrostatic Interaction for Their Enhanced Uptake and Anticancer Effect

In this study, dihydroartemisinin (DAR), an anticancer agent with low toxicity, was loaded into poly-lactic-co-glycolic acid (PLGA) nanoparticles. The obtained PLGA cores were then coated with chitosan (CS) and/or folic acid (FA) by electrostatic interactions to enhance their anticancer and cellular uptake properties. DAR-loaded PLGA nanoparticles were prepared by the solvent evaporation method. CS and FA solutions at different ratios were dispersed concurrently into the PLGA suspension to facilitate electrostatic interactions and form nanosuspensions. The physiochemical properties of nanoparticles such as average particle size (Z), polydispersity index (PDI), zeta potential (ZP), TEM image, X-ray diffraction, and encapsulation efficiency were determined. We then determined the role of FA and CS coating on the nanoparticle surface in cytotoxicity, cellular uptake, and apoptosis. We show that the resultant nanoparticles were spherical and uniform, with a coating layer containing FA and CS covering PLGA cores with a Z of 223.5±4.28 nm, PDI of 0.209±0.03, and ZP of 15.75±1.3 mV. Both FA and CS improved the cytotoxicity of nanoparticles compared to free DAR and PLGA nanoparticles in HL-60 and KB cancer cell lines. Further, FA enhanced the cellular uptake of nanoparticles to a greater extent than CS. However, CS contributed more to apoptosis induction than FA.

Plug-and-Play Continuous Gas Flow Assembly of Cysteine-Inserted AuCu Nanobimetals for Folate-Receptor-Targeted Chemo-Phototherapy.

Conjugatable nanobimetals exhibiting broadband light absorption for use as phototherapeutic platforms were assembled via a plug-and-play continuous gas flow route. Electrically produced AuCu nanobunches (NBs) under nitrogen gas flow were directly injected into cysteine (cys) solution through gas pressurization to mechanically spray the solution (AuCu into cys droplets). The sprayed droplets were then exposed to 185 nm UV light (higher photon energy [6.2 eV] than the work functions of Au [5.1 eV] and Cu [4.7 eV]) to initiate photoionization of AuCu NBs for subsequent electrostatic reaction with the SH- group of cys to form cys-inserted AuCu (AuCu-cys) platforms in a single-pass gas stream. These platforms exhibited broadband light absorption spectra because of hybridized interparticle plasmonic coupling and could be conjugated to folic acid (FA) when dispersed in FA solution to form highly dispersible, biocompatible, and cancer-targetable AuCu-cys-FA. This material was suitable for use in targeted phototherapy of folate-receptor (FR)-rich cancers via FR-mediated endocytosis, and loading doxorubicin (DOX) into AuCu-cys-FA (i.e., AuCu-cys-DOXFA) facilitated chemo-phototherapy because of photoresponsive anticancer drug release upon induction of hyperthermia.

Photo-protection and controlled release of folic acid using edible alginate/chitosan nanolaminates

The formation, characterization, photo-protective properties and release profiles of folic acid-loaded nanolaminated films were investigated by UV–visible spectroscopy, FTIR, Raman and SEM microscopy. Food-grade alginate/chitosan nanolaminates were obtained by the layer-by-layer technique and folic acid (FA) was incorporated by post-diffusion. The FA concentration of loading solutions and immersion time significantly affected the FA content in nanolaminates. The maximum FA loading was reached using FA solutions at 10 mg/mL for 30 min (54.4 μg/cm2), or 12.5 mg/mL for 120 min (≈70 μg/cm2). Nanolaminates containing FA were more stable under ultraviolet light exposure than non-encapsulated FA. The rate and concentration of FA released from nanolaminates were greater at buffer pH 7 than at pH 3, which might play a key role in the delivery and bioavailability of nutraceuticals. These results provide important information for the design of nanolaminates containing hydrophilic active compounds for food applications.

Electrochemical Oxidation Effect of Each Ascorbic Acid and Folic Acid on Lead Ions in Human Blood

Electrochemical studies by cyclic voltammetric (CV) method provide high potential for investigation of oxidant pollutant compounds such as Pb(II). Glassy carbon electrode (GCE) can be used for the potentiostatic analysis of the lead ions in different electrolyte especially human blood medium to studying the effect of the lead ions on the blood components. The results of this study were found that oxidation and reduction current peaks of lead ions in 1M KCl is high value and enhanced by adding ascorbic acid (AA) solution, while in human blood medium was disappearing the reduction current peak and enhance the oxidation current peak by lead ions. It means that lead ions in blood medium act as an oxidative reagent and causes problem in the decomposition of the blood component. Also, it was found that using folic acid (FA) solution with lead ions in blood medium causes the enhancement of reduction current peaks of lead ion and decreasing for oxidation current peaks, so this means that folic acid solution acts as antioxidative reagent in present of lead ions in blood medium, it may recommended to taking tablet of FA for the patients who suffers to lead pollution.

Inhibition of Photodegradation of Highly Dispersed Folic Acid Nanoparticles by the Antioxidant Effect of Transglycosylated Rutin.

We developed highly dispersible and photostable nanoparticles of vitamin, folic acid (FA). FA was wet bead milled with milling and dispersing adjuvants and transglycosylated compounds such as α-glucosyl hesperidin (Hesperidin-G) and rutin (Rutin-G), which solubilized FA. The milled slurries of FA particles with transglycosylated compounds consisted of nanosized particles with a median diameter of <100 nm. The lyophilized formulations of these slurries retained their nanometer size after resuspension in water with no aggregation. The apparent solubility of FA in these formulations was 100-fold higher than that of untreated FA. The solubilizing effect of Rutin-G may affect the particle size reduction and dispersibility of FA. The photostability results showed that the strong antioxidant activity of Rutin-G substantially increased the photostability of FA solution. On the basis of these results, bead milling of FA with Rutin-G is a promising technique for developing highly dispersible, photostable nanoparticle FA formulations.

Investigating the Fluorescence Quenching of Doxorubicin in Folic Acid Solutions and its Relation to Ligand-Targeted Nanocarriers.

Folic acid (FA) is one of the most utilized moieties in active (ligand) drug delivery. The folate receptor is widely expressed on the surface of several cell lines and tumors; including ovarian, brain, kidney, breast, and lung cancers. During our previous experiments with Doxorubicin (Dox) encapsulated in folate-targeted micelles, we found that flow cytometry underestimated the amount of drug that accu- mulates inside cells. We attributed this effect to the quenching of Dox by FA and herein investigate this phenomenon in an attempt to obtain a correction factor that could be applied to the fluorescence of Dox in the presence of FA. Initially, we examine the effect of pH on the fluorescence spectra of FA, Dox, equimolar solutions of FA and Dox in water, HCI (0.1 M), and NaOH (0.1 M) solutions. We then measure the effect of the gradual increase of FA concentration on the fluorescence intensity of Dox in phosphate-buffered saline (PBS) solutions (pH of 7.4). Using the Stern-Volmer equation, we estimate the association constant of FA-Dox to be K(SV) = 1.5 x 10(4) M(-1). Such an association constant indicates that at the concentrations of FA used in targeted drug delivery systems, a significant concentration of Dox exists as FA-Dox complexes with a quenched fluorescence. Therefore, we conclude that when Dox is used in FA-active drug delivery systems, a correction factor is needed to predict the correct fluorescence intensity of agent in vitro and in vivo.

Mechanism of folic acid radiolysis in aqueous solution

Folates compounds are a B group vitamin vital for important biochemical processes like DNA synthesis and repair and in certain biological reactions as a cofactor. Folic acid (FA) is composed of a pteridine ring, p-aminobenzoic acid and glutamate moieties. Separately, the three moieties have no vitamin activity. Folate deficiency can lead to increased risk of several pathologies. FA is known to be a sensitive compound, easily degraded by pH, light, heat and food processing. Food irradiation is a process exposing food to ionizing radiations to reduce storage losses, extend shelf life and microbiological safety. Radiation treatment produces oxygen radicals and thereby induces oxidative damage in biomolecules such as proteins, lipids, DNA and vitamins. In the present work, aqueous FA solutions are submitted to electron-beam (E-beam) radiation in a dose range of 0.25–10 kGy. Upon irradiation, main FA radio-products are quantified by HPLC. E-beam processing undergoes radiolysis to yield some known FA photoproducts and also new radio-products are formed: 6-(hydroxymethyl)pterin and N-(4-nitrobenzoyl)-l-glutamic acid. A radio-degradation pathway of FA is also discussed.

In vitro effects of zinc and folic acid on the expressions of Neurogenin 3, Kruppel-like factor 4, c-Myc, Nanog, Nestin and POU class 5 homeobox 1 genes

Objective: Genes are regulated at multiple levels by using nutritional factors during neurogenesis and gliogenesis in brain development. Folic acid (FA)and zinc regulate the expressions of some genes which participate in brain development as nutritional factors. So, we aimed to find the effect of FA and zinc on the expression levels of neurogenin 3 (NGN3), Kruppel-like factor 4 (Klf4), c-Myc, nanog, POU class 5 homeobox 1-Pou5F1 (Oct4), and Nestin in mouse fetal brain tissue in neural plate phase at gestational day 7 (GD7)and in fetal brain tissue at GD20. Methods: All the tissues were cultured primarily. FA and zinc solutions were added. Real time-polymerase chain reaction was performed in RNA obtained from in each sample. Results: FA has no effect on GD7 mouse neural plate tissue and GD20 mouse fetal brain tissue. Zinc has no effect on GD7 mouse neural plate tissue. Zinc increased the expressions of NGN3, Klf4, nanog, Nestin, and Oct4 genes on GD20 mouse fetal brain tissue. Conclusion: This in vitro study represents that zinc is important in the expressions of NGN3, Klf4, Nanog, Nestin, and Oct4 genes in the late phase of pregnancy. The stimulator effect of Zinc on the expression levels of these genes may show us the possible role of zinc in fetal brain development in the late phase of pregnancy.