Ultrasensitive SERS quantitative detection of antioxidants via diazo derivatization reaction and deep learning for signal fluctuation mitigation.

Synthetic antioxidants serve as essential protectors against oxidation and deterioration of edible oils, however, prudent evaluation is necessary regarding potential health risks associated with excessive intake. The direct adsorption of antioxidants onto conventional surface-enhanced Raman scattering (SERS) substrates is challenging due to the presence of phenolic hydroxyl groups in their molecular structures, resulting in weak Raman scattering signals and rendering direct SERS detection difficult. In this study, a diazo derivatization reaction was employed to enhance SERS signals by converting antioxidant molecules into azo derivatives, enabling the amplification of the weak Raman scattering signals through the strong vibrational modes induced by the N = N double bond. The resulting diazo derivatives were characterized using UV-visible absorption and infrared spectroscopy, confirming the occurrence of diazo derivatization of the antioxidants. The proposed method successfully achieved the rapid detection of three commonly used synthetic antioxidants, namely butylated hydroxyanisole (BHA), tert-butylhydroquinone (TBHQ), and propyl gallate (PG) on interfacial self-assembled gold nanoparticles. Furthermore, rapid predictions of BHA, PG, and TBHQ within the concentration range of 1 × 10-6 to 2 × 10-3 mol/L were achieved by integrating a convolutional neural network model. The predictive range of this model surpassed the traditional quantitative method of manually selecting characteristic peaks, with linear coefficients (R2) of 0.9992, 0.9997, and 0.9997, respectively. The recovery of antioxidants in real soybean oil samples ranged from 73.0 % to 126.4 %. Based on diazo derivatization, the proposed SERS method eliminates the need for complex substrates and enables the analysis and determination of synthetic antioxidants in edible oils within 20 min, providing a convenient analytical approach for quality control in the food industry.

Colorimetric sensor array based on CoOOH nanoflakes for rapid discrimination of antioxidants in food.

The identification of synthetic antioxidants has considerable significance in food safety. Here, we described the development of a colorimetric sensor array for rapid detection of eight antioxidants in food through the redox reaction between CoOOH and antioxidants in the presence of colorimetric signal indicators. The CoOOH nanoflakes exhibited high catalytic oxidation activity and can independently catalyze oxidation signal indicators showing different colors. The color reaction was inhibited to different degrees in the presence of antioxidants, which resulted in distinct signal response patterns for their discrimination. The method showed good linearity in the range from 50 to 1000 nM for butylated hydroxytoluene (BHT), butylhydroxyanisole (BHA), propyl gallate (PG) and tert-butyl hydroquinone (TBHQ). Moreover, different proportions of antioxidants were located in the middle pattern of each single antioxidant, and showed certain linear relationships among different concentration ratios. Finally, the proposed colorimetric sensor array was used for practical applications where TBHQ and BHT were detected in biscuits and sausages, and BHA and PG were detected in fried pork kebabs, respectively. The results were further confirmed by high-performance liquid chromatography, which demonstrated the great potential of the colorimetry sensor array for practical applications.

Using Physical Organic Chemistry Knowledge to Predict Unusual Metabolites of Synthetic Phenolic Antioxidants by Cytochrome P450.

Biotransformation, especially by human CYP450 enzymes, plays a crucial role in regulating the toxicity of organic compounds in organisms, but is poorly understood for most emerging pollutants, as their numerous "unusual" biotransformation reactions cannot retrieve examples from the textbooks. Therefore, in order to predict the unknown metabolites with altering toxicological profiles, there is a realistic need to develop efficient methods to reveal the "unusual" metabolic mechanism of emerging pollutants. Combining experimental work with computational predictions has been widely accepted as an effective approach in studying complex metabolic reactions; however, the full quantum chemical computations may not be easily accessible for most environmentalists. Alternatively, this work practiced using the concepts from physical organic chemistry for studying the interrelationships between structure and reactivity of organic molecules, to reveal the "unusual" metabolic mechanism of synthetic phenolic antioxidants catalyzed by CYP450, for which the simple pencil-and-paper and property-computation methods based on physical organic chemistry were performed. The phenol-coupling product of butylated hydroxyanisole (BHA) (based on spin aromatic delocalization) and ipso-addition quinol metabolite of butylated hydroxytoluene (BHT) (based on hyperconjugative effect) were predicted as two "unusual" metabolites, which were further confirmed by our in vitro analysis. We hope this easily handled approach will promote environmentalists to attach importance to physical organic chemistry, with an eye to being able to use the knowledge gained to efficiently predict the fates of substantial unknown synthesized organic compounds in the future.

Evaluation of the Antioxidant and Antiradical Properties of Some Phyto and Mammalian Lignans.

In this study, the antioxidant and antiradical properties of some phyto lignans (nordihydroguaiaretic acid, secoisolariciresinol, secoisolariciresinol diglycoside, and α-(-)-conidendrin) and mammalian lignans (enterodiol and enterolactone) were examined by different antioxidant assays. For this purpose, radical scavenging activities of phyto and mammalian lignans were realized by 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulphonic acid) radical (ABTS•+) scavenging assay and 1,1-diphenyl-2-picrylhydrazyl radical (DPPH) scavenging assay. Additionally, the reducing ability of phyto and mammalian lignans were evaluated by cupric ions (Cu2+) reducing (CUPRAC) ability, and ferric ions (Fe3+) and [Fe3+-(TPTZ)2]3+ complex reducing (FRAP) abilities. Also, half maximal inhibitory concentration (IC50) values were determined and reported for DPPH• and ABTS•+ scavenging influences of all of the lignan molecules. The absorbances of the lignans were found in the range of 0.150-2.320 for Fe3+ reducing, in the range of 0.040-2.090 for Cu2+ reducing, and in the range of 0.360-1.810 for the FRAP assay. On the other hand, the IC50 values of phyto and mammalian lignans were determined in the ranges of 6.601-932.167 µg/mL for DPPH• scavenging and 13.007-27.829 µg/mL for ABTS•+ scavenging. In all of the used bioanalytical methods, phyto lignans, as secondary metabolites in plants, demonstrated considerably higher antioxidant activity compared to that of mammalian lignans. In addition, it was observed that enterodiol and enterolactone exhibited relatively weaker antioxidant activities when compared to phyto lignans or standard antioxidants, including butylated hydroxytoluene (BHT), butylated hydroxyanisole (BHA), Trolox, and α-tocopherol.

Synthetic phenolic antioxidants: Metabolism, hazards and mechanism of action.

Synthetic phenolic antioxidants can interact with peroxides produced by food. This paper reviews correlation between BHA, BHT and TBHQ metabolism and harms they cause and provides a theoretical basis for rational use of BHA, BHT and TBHQ in food, and also put some attention on the transformation and metabolic products of PG. We introduce BHA, BHT, TBHQ, PG and their possible metabolic pathways, and discuss possible harms and their specific mechanisms responsible. Excessive addition or incorrect use of synthetic phenolic antioxidants results in carcinogenicity, cytotoxicity, oxidative stress induction and endocrine disrupting effects, which warrant attention. BHA carcinogenicity is related to production of metabolites TBHQ and TQ, and cytotoxic effect of BHA is the main cause of apoptosis induction. BHT carcinogenicity depends on DNA damage degree, and tumour promotion is mainly related to production of quinone methylation metabolites. TBHQ carcinogenicity is related to induction of metabolite TQ and enzyme CYP1A1.

Electrochemical sensor for determination of butylated hydroxyanisole (BHA) in food products using poly O-cresolphthalein complexone coated multiwalledcarbon nanotubes electrode.

In this study, we have reported an electrochemical sensor for the determination of butylated hydroxyanisole (BHA) by electropolymerization of O-cresolphthalein complexone (OC) over the multiwalled carbon nanotubes (MWCNTs). In order to confirm the surface morphology, oxidation states, functional groups and charge transfer property of POC/MWCNTs electrode, the resulting POC film with MWCNTs electrode was characterized by spectroscopy, microscopy, and electrochemical techniques. The fabricated electrode was evaluated for its electrochemical performance in oxidation of BHA and the study showed that at POC/MWCNTs electrodes BHA oxidation occurred at 0.27 V. POC/MWCNTs electrode has shown a linear range for the detection of BHA from 0.33 µM to 110 µM with the detection limit of 0.11 µM (S/N = 3). Amperometric determination of BHA was also done using chronoamperometric techniques and the result was found to be linear. The real time analysis of sensors is also validated by analysing the packed potato chips samples.

Identification of In Vitro Metabolites of Synthetic Phenolic Antioxidants BHT, BHA, and TBHQ by LC-HRMS/MS.

Butylated hydroxytoluene (BHT) and its analogs, butylated hydroxyanisole (BHA) and tert-butyl-hydroquinone (TBHQ), are widely used synthetic preservatives to inhibit lipid oxidation in the food, cosmetic and pharmaceutical industries. Despite their widespread use, little is known about their human exposure and related biotransformation products. The metabolism of these compounds was investigated using in vitro incubations with human and rat liver fractions. Liquid chromatography coupled to high-resolution tandem mass spectrometry was employed to detect and characterize stable and reactive species formed via oxidative metabolism, as well as phase II conjugates. Several oxidative metabolites have been detected, as well as glutathione, glucuronide, and sulfate conjugates, many of which were not previously reported. A combination of accurate mass measurements, MS/MS fragmentation behavior, and isotope-labeling studies were used to elucidate metabolite structures.

Properties and Application of Multifunctional Composite Polypropylene-Based Films Incorporating a Combination of BHT, BHA and Sorbic Acid in Extending Donut Shelf-Life.

To extend the shelf-life of packaged donut without the addition of preservative, polypropylene-based active composite films loaded with a combination of sorbic acid, BHA and BHT were prepared by the extrusion moulding method: T1 (Control-pure PP-film), T2 (PP-BHT1%-SA2%), T3 (PP-BHA3%-SA2%) and T4 (PP-BHT1%-BHA1%-SA2%). The incorporation of active additives enhanced water vapour permeability (WVP) and increased oxygen permeability of films. Active films had higher antioxidant activity than pure PP in the order T4 > T2 > T3 (89.11, 83.40 and 79.16%). In vitro examinations demonstrated a significant antibacterial effect on Escherichia coli and S. aureus growth. Overall migration was not significantly different for watery food simulants, while in acidic and fatty foods increased it significantly. The effect of the active films on the fried and packaged donut samples showed significantly higher moisture contents and peroxide values, while acidity was lower. T2 film is proposed due to the preservation of the intrinsic properties of the film, increasing the storage period up to 25 to 50 days.

Alkylated Sesamol Derivatives as Potent Antioxidants.

Sesamol is a phenolic derivative. Its antioxidant activity is low than that of Trolox and depends on benzodioxole moiety. Thus, a molecular modification strategy through alkylation, inspired by natural and synthetic antioxidants, was studied by molecular modeling at the DFT/B3LYP level of theory by comparing the 6-31+G(d,p) and 6-311++G(2d,2p) basis sets. All proposed derivatives were compared to classical related antioxidants such as Trolox, t-butylated hydroxytoluene (BHT) and t-butylated hydroxyanisole (BHA). According to our results, molecular orbitals, single electron or hydrogen-atom transfers, spin density distributions, and alkyl substitutions at the ortho positions related to phenol moiety were found to be more effective than any other positions. The trimethylated derivative was more potent than Trolox. t-Butylated derivatives were stronger than all other alkylated derivatives and may be new alternative forms of modified antioxidants from natural products with applications in the chemical, pharmaceutical, and food industries.

Antioxidant Activity of Pastinaca sativa L. ssp. sylvestris [Mill.] Rouy and Camus Essential Oil.

In the last decade, there has been growing interest in the food industry in replacing synthetic chemicals with natural products with bioactive properties. This study's aims were to determine the chemical composition and the antioxidant properties of the essential oil of Pastianica sylvestris. The essential oil was isolated with a yield of 0.41% (w/v) by steam distillation from the dried seeds and subsequently analysed by GC-MS. Octyl acetate (78.49%) and octyl hexanoate (6.68%) were the main components. The essential oil exhibited an excellent activity for the inhibition of primary and secondary oxidation products for cold-pressed sunflower oil comparable with butylated hydroxyanisole (BHA) and butylated hydroxytoluene (BHT), which were evaluated using peroxide and thiobarbituric acid values. The antioxidant activity of the essential oil was additionally validated using DPPH radical scavenging (0.0016 ± 0.0885 mg/mL), and ß-carotene-linoleic acid bleaching assays. Also, the amounts of total phenol components (0.0053 ± 0.0023 mg GAE/g) were determined.

Herbal Extracts Incorporated into Shortbread Cookies: Impact on Color and Fat Quality of the Cookies.

This study aimed at determining the effect of aqueous ethanolic extracts from lemon balm, hyssop and nettle, and butylated hydroxyanisole (BHA) on properties of shortbread cookies. This was achieved by instrumental measurements of color and sensory properties of the cookies directly after baking and by determination of peroxide (PV) and p-anisidine (p-AnV) values, and specific extinction coefficients (K232 and K268 values) for fat extracted from the cookies stored for 3 months at room temperature. Increase of the herbal extracts' concentration from 0.02% to 0.2% in the cookies caused a reduction of L* (the brightness) and a* values (the red coordinate), while b* values (the yellow coordinate) increased when the cookies were enriched with lemon balm and nettle extracts. Among the cookies studied, those prepared with BHA and 0.1 and 0.2% addition of lemon balm extracts were characterized by the highest scores for aroma, taste, and overall acceptability. Incorporation of BHA and 0.02% hyssop extract into the cookies caused a decrease of PV values (the peroxide value) for fat extracted from the cookies after 3 months of their storage compared to a (control) sample without additives and produced the lowest K232 values. Changes in the p-AnV values for the fat samples studied occurred gradually and slowly during the storage and the obtained values were lower compared to the control sample. All of the studied fat samples also showed a higher ability to scavenge DPPH radicals than the control sample. Considering both PV and p-AnV values as indicators of fat oxidation, BHA protected fat extracted from cookies against oxidation better than the herbal extracts used.

Inhibition Mechanism of Catechin, Resveratrol, Butylated Hydroxylanisole, and Tert-Butylhydroquinone on Carboxymethyl 1,2-Dipalmitoyl-sn-Glycero-3-Phosphatidylethanolamine Formation.

It is important to inhibit the food-derived, potentially hazardous chemical glycated lipids by natural products. A model system was established and the products are identified to study the inhibitory mechanism of four types of catechin, resveratrol (RES), and the synthetic antioxidants butylated hydroxylanisole (BHA) and tert-butylhydroquinone (TBHQ) on the formation of carboxymethyl 1,2-dipalmitoyl-sn-glycero-3-phosphatidylethanolamine (CM-DPPE) by determining hydroxyl radical (OH·), Amadori-1,2-dipalmitoyl-sn-glycero-3-phosphatidylethanolamine (Amadori-DPPE) and glyoxal (GO). The results show that the inhibitory rates of catechin and RES on the content of CM-DPPE in the model system are higher than those of BHA and TBHQ. There are at least two inhibitory mechanisms of antioxidants on CM-DPPE. (1) Antioxidants scavenge OH·, which blocks the process of Amadori-DPPE oxidation to form CM-DPPE. (2) Antioxidants trap GO, which blocks the reaction between GO and DPPE to form CM-DPPE. This research will reveal the inhibitory mechanisms of natural antioxidants on glycated lipids from the aspect of scavenging OH· and trapping GO. PRACTICAL APPLICATION: Food manufacturers should pay attention on the production of glycated lipids in food processing. This study will provide the theoretical basis for the use of natural products to inhibit the formation of food-derived glycated lipids. Natural products, such as catechin and resveratrol, can substitute chemical synthesis antioxidants, such as butylated hydroxylanisole and tert-butylhydroquinone, in food processing, which inhibit the formation of glycated lipids.

Butylated hydroxyanisole isomers induce distinct adipogenesis in 3T3-L1 cells.

Butylated hydroxyanisole (BHA) isomers, as the widely used anthropogenic antioxidants in food, have been revealed to induce endocrine disrupting effects, while the mechanism how BHA isomers regulate the lipogenic differentiation remains to be elucidated. Using 3T3-L1 differentiation model, the effects of BHA isomers, including 2-tert-butyl-4-hydroxyanisole (2-BHA), 3-tert-butyl-4-hydroxyanisole (3-BHA) and their mixture (BHA), on adipogenesis were tested. The results showed that 3-BHA and BHA promoted adipocyte differentiation and enhanced the cellular lipid accumulation through the regulation of the transcriptional and protein levels of the adipogenetic biomarkers, while 2-BHA had no effect. The effective window for 3-BHA induced lipogenesis was the first four days during 3T3-L1 differentiation. BHA isomers showed no binding affinities for peroxisome proliferator activated receptor γ (PPARγ). Instead, the upstream of PPARγ signaling pathway, i.e. the phosphorylation of cAMP-response element binding protein (CREB), upregulation of CAAT/enhancer-binding proteins ß (C/EBPß) and elevated cell proliferation during postconfluent mitosis stage were induced by 3-BHA exposure. Altogether, this study revealed the adipogenic effect of 3-BHA through interference with the upstream events of the PPARγ signaling pathway. The authorized usage of BHA as food additives and its occurrence in human sera can potentially contribute to the incidence of obesity, which is of high concern.

Microencapsulated food-grade antioxidant applied as a preservative of peanut seed quality in microcosm- and pilot-scale trials.

BACKGROUND: In Argentina, peanuts are stored for 3-6 months. It is important to avoid proliferation of fungi and insect pests during this period. In this study, the potential of butylated hydroxyanisole (BHA) microcapsules to conserve peanut kernels was evaluated in microcosms and on a pilot scale. RESULTS: In microcosm assays, microcapsules containing BHA at a dose of 1802 µg g-1 reduced 37% of total fungal count. Higher reductions (77-100%) were obtained with a combined treatment with BHA formulation (1802 µg g-1 ) plus fungicide (methyl thiophanate 0.0100 g L-1  and metalaxyl 0.0133 g L-1 ). However, germination levels of peanut seeds treated with the BHA formulation were less than 6% throughout the incubation time. In pilot-scale trials, the storage conditions allowed the control of fungal development and insect proliferation. Quantifiable levels of BHA were also detected throughout the entire storage period. The combined treatment significantly reduced fungal contamination at 2 months of storage (C1-2015: 37.41%; C1-2016: 28.48%; C2-2016: 45.02%). Seed germination of unshelled stored peanuts was not affected by the formulation. CONCLUSION: The application of the BHA formulation during storage combined with pre-seeding treatment could be an appropriate strategy to maintain the quality of the peanut kernels destined for seed. © 2018 Society of Chemical Industry.

Butylated hydroxyanisole encapsulated in gelatin fiber mats: Volatile release kinetics, functional effectiveness and application to strawberry preservation.

Butylated hydroxyanisole (BHA) encapsulated in gelatin (GA) (GA-BHA) fiber mats were fabricated via electrospinning technique and applied to strawberry preservation. The volatile release kinetics and functional effectiveness of the mats were investigated. BHA was high efficiently encapsulated in GA fibers and the antioxidant activity of BHA could be well protected. The encapsulation of BHA enhanced the stability of GA and favored structure transition of GA from random coil and ß-turns to α-helix and ß-sheet. The GA-BHA mats showed good antibacterial activity against Staphylococcus aureus, and the predominant volatile release mechanism of BHA from mats was Fickian diffusion. Furthermore, the mats also showed broad-spectrum antifungal activity against four mould genera (Rhizopus sp., Mucor sp., Aspergillus sp. and Penicillium sp.). The shelf-life of strawberry can be prolonged effectively in the presence of GA-BHA mats during storage. Results suggested that the GA-BHA mats may have a great potential in active food packaging.

Biologically and chemically important hydrazino-containing imidazolines as antioxidant agents.

Biologically and chemically useful hydrazinoimidazolines were evaluated as antioxidant and antihaemolytic agents. 1,1-Diphenyl-2-picrylhydrazyl radical (DPPH•), galvinoxyl radical (GOR), nitric oxide (NO) and hydrogen peroxide (H2O2) scavenging assays, ferric ions reducing power assay, and ex vivo model of rat erythrocytes exposed to 2,2'-azobis(2-methylpropionamidine)dihydrochloride (AAPH) or H2O2 were used. The most potent DPPH• scavengers proved to be hydrazinoimidazolines 3, 2, and 4, revealing excellent antiradical effects - superior or comparable to that of all antioxidant standards used. Moreover, these molecules showed strong NO neutralising potencies - better to that of ascorbic acid (AA) (3), 6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid (Trolox) (3 and 2), butylated hydroxytoluene (BHT) (3 and 2), and butylated hydroxyanisole (BHA) (3, 2, and 4). Compound 4 was also effective in GOR scavenging. The excellent scavenger of GOR, NO, and H2O2 proved to be structure 5, with the potency superior or comparable to the majority of antioxidant standards used. In turn, compound 9 was effective in H2O2 and GOR neutralisation. All hydrazinoimidazolines revealed the reducing power that is higher than BHT. Moreover, the protective effects of most test compounds on oxidatively stressed erythrocytes were observed. Some structure-activity relationships were disclosed. A significance of the primary hydrazino group on antioxidant effects was confirmed. The most likely DPPH• and GOR scavenging mechanisms for test compounds were propound. Among all the investigated molecules, hydrazinoimidazolines 5, 3, 2, 4, and 9, due to their excellent or good antiradical activities, can represent promising antioxidant candidates with prospective utility for prevention of diseases related to reactive oxygen/nitrogen species.

Impact of antioxidant additives on the performance and emission characteristics of C.I engine fuelled with B20 blend of rice bran biodiesel.

This manuscript presents the impact of addition of antioxidant additives to rice bran biodiesel blend on the performance and emission characteristics of compression ignition (C.I) engine. Rice bran methyl ester (RBME) was produced from rice bran oil by transesterification using sodium hydroxide as catalyst. An experimental investigation was conducted on a single-cylinder four-stroke C.I engine to analyze the performance and emission characteristics of rice bran methyl ester (RBME) blended with diesel at 20% by volume (B20) with and without addition of 1000 ppm of two monophenolic antioxidant additives, butylated hydroxyanisole (BHA) and butylated hydroxytoluene (BHT). The results showed that the BHA- and BHT-treated B20 blend decreased the brake specific fuel consumption (BSFC) by 2.1 and 1.2% and increased the brake thermal efficiency (BTE) by 1.04 and 0.5% compared to B20. The BHA- and BHT-treated B20 blend produced mean reductions in NOx emission of 12.2 and 9.6%, respectively, compared to B20. The carbon monoxide (CO) and hydrocarbon (HC) emissions of BHA- and BHT-treated B20 were increased by 14.8-16.6% and 10.6-11.2%, respectively, compared to B20. However the emission levels were lower than those of diesel.

Synthesis and Application of a New Amphiphilic Antioxidant.

A new amphiphilic antioxidant (tannyl stearate) derived from reaction of tannic acid with stearic acid was synthesized in order to improve tannic acid solubility in lipid materials. This reaction gives many products having different degree of esterification (tannyl mono, di, tri, tetra, penta, hexa, hepta……stearate) which were separated using silica gel column chromatography and tentative identification was carried out using thin layer chromatography (TLC). The intrinsic viscosities (η) were used to differentiate between the different molecular weight of the produced esters1). Tannyl penta stearate is assumed to be the most suitable amphiphilic antioxidant derivative, where those derivatives with less degree of esterification would be less soluble in fat, and those of higher degree of esterification would exhaust more hydroxyl group that cause decreases of antioxidant activity. The structure of tannyl penta stearate was approved depending on its chemical analysis and spectral data (IR, H1 NMR,). The emulsification power of tannyl penta stearate was then determined according to method described by El-Sukkary et al.2), in order to prove its amphiphilic property. Then tannyl penta stearate was tested for its antioxidant and radical scavenging activities in three different manners, those are, lipid oxidation in sunflower oil using Rancimat, (DPPH) free radical scavenging and total antioxidant activity. {Pure tannic acid (T), butylhydroxyanisol (BHA) and butylhydroxytoluene (BHT) were used as reference antioxidant radical saving compounds}. Then tannyl penta stearate was added to sunflower oil, frying process was carried out and all physicochemical parameters of the oil were considered, and compared to other reference antioxidant in order to study the effect of this new antioxidant toward oil stability. Acute oral toxicity of the tannyl penta stearate was carried out using albino mice of 21-25 g body weight to determine its safety according to the method described by Goodman et al.3). Also liver and kidney functions of those mice were checked. Thus it could be concluded that the addition of tannyl penta stearate to frying oils offers a good protection against oxidation. The effectiveness of tannyl penta stearate as lipid antioxidant has been attributed mainly to its stability at high temperature. And according to acute lethal toxicity test tannyl penta stearate was found to be a safe compound that can be used as food additive.

Effect of inorganic mesoporous carriers on 1-palmitoyl-2-linoleoyl-3-acetyl-rac-glycerol-loaded solid self-emulsifying drug delivery system: Physicochemical characterization and bioavailability in rats.

The purpose of this study was to assess the impact of inorganic mesoporous carriers on the physicochemical properties and oral bioavailability of 1-palmitoyl-2-linoleoyl-3-acetyl-rac-glycerol (PLAG)-loaded solid self-emulsifying drug delivery system (solid SEDDS). Numerous PLAG-loaded solid SEDDS formulations were prepared by spray drying technique with sodium laurylsulfate (SLS), butylated hydroxyanisole (BHA) and inorganic mesoporous materials as a surfactant, antioxidant and solid carrier, respectively. The mesoporous materials, such as calcium silicate, silicon dioxide and magnesium aluminosilicate were used as the solid carriers. Their physicochemical properties, solubility, dissolution and pharmacokinetic studies in rats were performed compared with drug alone. Three solid SEDDSs composed of PLAG/BHA/SLS/mesopous carrier at the weight ratio of 1:0.0002:0.25:0.5 resulted in a small emulsion droplet and excellent drug loading efficiency. The solid SEDDS formulations prepared with calcium silicate and silicon dioxide showed a rough-surfaced irregular shape and rough-surfaced spheres, respectively. Magnesium aluminosilicate generated a sticky powder, due to its relatively low specific surface area, resulting in insufficient adsorption of PLAG. These solid SEDDSs improved the solubility, dissolution and oral bioavailability of PLAG. Ultimately, the solid SEDDS prepared with silicon dioxide resulted in the best drug loading efficiency, shape, solubility, dissolution and oral bioavailability due to its great specific surface area. Therefore, mesoporous carriers with different specific surface areas markedly influenced the physicochemical properties, solubility, dissolution and oral bioavailability of PLAG-loaded solid SEDDS.

Inhibition of Aβ(1-42)Oligomerization, Fibrillization and Acetylcholinesterase Activity by Some Anti-Inflammatory Drugs: An in vitro Study.

BACKGROUND: Number of contradictory reports are available on the effects of antiinflammatory drugs on Alzheimer's disease (AD) including beneficial, adverse and stage dependent effects. We provide insights of the effects exerted by some anti-inflammatory drugs on the chemistry of AD. METHODS: Three different doses of dexamethasone (0.015, 0.030, 0.060 µM), piroxicam (5, 7.5, 10 µM), indomethacin (1, 1.25, 1.50 µM), diclofenac (0.6, 0.8, 1.0 µM), aspirin (90, 120, 150 µM) and celecoxib (30, 45, 60 µM) were used. Rivastigmine, methylene blue and butylated hydroxyanisole were used as standard drug, oligomerization inhibitor and antioxidant, respectively. Oligomerization and fibrillization reactions were performed using Aß1-42 peptides. Results-Indomethacin and aspirin mainly inhibited oligomerization, while rivastigmine and piroxicam inhibited fibrillization. Diclofenac and celecoxib inhibited both oligomerization and fibrillization almost equally. Dexamethasone showed poor efficiency on both the processes, but exert comparably more inhibition of oligomerization than fibrillization. Inhibition of acetylcholinesterase activity was also potent and was in the following order: celecoxib> piroxicam> diclofenac> aspirin> indomethacin> dexamethasone. Strong radical scavenging (More than 50%) activity was showed by indomethacin and aspirin for NO radicals. CONCLUSION: Present study consistently revealed that anti-inflammatory drugs have potential to Modulate chemistry of AD progression. Inclusion of anti-inflammatory drugs in low doses along with routine therapies may provide therapeutically and economically more efficient therapies for AD. However, further studies are warranted, because the overall therapeutic effect seems to be the function of stage of disease, dose of drug, main underlying mechanism of action(s).