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1.
AAPS PharmSciTech ; 25(5): 113, 2024 May 15.
Article in English | MEDLINE | ID: mdl-38750336

ABSTRACT

Transport of oral nanocarriers across the GI epithelium necessitates transport across hydrophilic mucus layer and the hydrophobic epithelium. Based on hydrophobic-hydrophilic balance, Curcumin-Lipomer (lipid-polymer hybrid nanoparticles) comprising hydrophobic stearic acid and hydrophilic Gantrez™ AN 119 (Gantrez) were developed, by a radical in-situ approach, to successfully traverse both barriers. A monophasic preconcentrate (Cur-Pre) comprising Cur (Curcumin), stearic acid, Gantrez and stabilizers, prepared by simple solution, was added to an aqueous phase to instantaneously generate Curcumin-Lipomer (Cur-Lipo) of nanosize and high entrapment efficiency (EE). Cur-Lipo size and EE was optimized by Box-Behnken Design. Cur-Lipomers of varying hydrophobic-hydrophilic property obtained by varying the stearic acid: Gantrez ratio exhibited size in the range 200-400 nm, EE > 95% and spherical morphology as seen in the TEM. A decrease in contact angle and in mucus interaction, evident with increase in Gantrez concentration, indicated an inverse corelation with hydrophilicity, while a linear corelation was observed for mucopenetration and hydrophilicity. Cur-SLN (solid lipid nanoparticles) which served as the hydrophobic reference revealed contact angle > 90°, maximum interaction with mucus and minimal mucopenetration. The ex-vivo permeation study through chicken ileum, revealed maximum permeation with Cur-Lipo1 and comparable and significantly lower permeation of Cur-Lipo1-D and Cur-SLN proposing the importance of balancing the hydrophobic-hydrophilic property of the nanoparticles. A 1.78-fold enhancement in flux of hydrophobic Cur-SLN, with no significant change in permeation of the hydrophilic Cur-Lipomers (p > 0.05) following stripping off the mucosal layer was observed. This reiterated the significance of hydrophobic-hydrophilic balance as a promising strategy to design nanoformulations with superior permeation across the GI barrier.


Subject(s)
Curcumin , Drug Carriers , Hydrophobic and Hydrophilic Interactions , Intestinal Mucosa , Nanoparticles , Stearic Acids , Nanoparticles/chemistry , Administration, Oral , Animals , Stearic Acids/chemistry , Curcumin/administration & dosage , Curcumin/pharmacokinetics , Curcumin/chemistry , Intestinal Mucosa/metabolism , Drug Carriers/chemistry , Particle Size , Lipids/chemistry , Polymers/chemistry , Biological Transport/physiology , Polyvinyls/chemistry
2.
Food Res Int ; 186: 114355, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38729701

ABSTRACT

In this study, five C18 fatty acids (FA) with different numbers of double bonds and configurations including stearic acid (SA), oleic acid (OA), elaidic acid (EA), linoleic acid (LA), and α-linolenic acid (ALA), were selected to prepare highland barely starch (HBS)-FA complexes to modulate digestibility and elaborate the underlying mechanism. The results showed that HBS-SA had the highest complex index (34.18 %), relative crystallinity (17.62 %) and single helix content (25.78 %). Furthermore, the HBS-C18 FA complexes were formed by EA (C18 FA with monounsaturated bonds) that had the highest R1047/1022 (1.0509) and lowest full width at half-maximum (FWHM, 20.85), suggesting good short-range ordered structure. Moreover, all C18 FAs could form two kinds of V-type complexes with HBS, which can be confirmed by the results of CLSM and DSC measurements, and all of them showed significantly lower digestibility. HBS-EA possessed the highest resistant starch content (20.17 %), while HBS-SA had the highest slowly digestible starch content (26.61 %). In addition, the inhibition of HBS retrogradation by fatty acid addition was further proven, where HBS-SA gel firmness (37.80 g) and aging enthalpy value were the lowest, indicating the most effective. Overall, compounding with fatty acids, especially SA, could be used as a novel way to make functional foods based on HBS.


Subject(s)
Digestion , Fatty Acids , Hordeum , Oleic Acid , Starch , Starch/chemistry , Fatty Acids/analysis , Fatty Acids/chemistry , Hordeum/chemistry , Oleic Acid/chemistry , Stearic Acids/chemistry , Linoleic Acid/chemistry , alpha-Linolenic Acid/chemistry , Oleic Acids
3.
ACS Nano ; 18(18): 11813-11827, 2024 May 07.
Article in English | MEDLINE | ID: mdl-38657165

ABSTRACT

Nanoenabled strategies have recently attracted attention as a sustainable platform for agricultural applications. Here, we present a mechanistic understanding of nanobiointeraction through an orthogonal investigation. Pristine (nS) and stearic acid surface-modified (cS) sulfur nanoparticles (NPs) as a multifunctional nanofertilizer were applied to tomato (Solanum lycopersicumL.) through soil. Both nS and cS increased root mass by 73% and 81% and increased shoot weight by 35% and 50%, respectively, compared to the untreated controls. Bulk sulfur (bS) and ionic sulfate (iS) had no such stimulatory effect. Notably, surface modification of S NPs had a positive impact, as cS yielded 38% and 51% greater shoot weight compared to nS at 100 and 200 mg/L, respectively. Moreover, nS and cS significantly improved leaf photosynthesis by promoting the linear electron flow, quantum yield of photosystem II, and relative chlorophyll content. The time-dependent gene expression related to two S bioassimilation and signaling pathways showed a specific role of NP surface physicochemical properties. Additionally, a time-dependent Global Test and machine learning strategy applied to understand the NP surface modification domain metabolomic profiling showed that cS increased the contents of IA, tryptophan, tomatidine, and scopoletin in plant leaves compared to the other treatments. These findings provide critical mechanistic insights into the use of nanoscale sulfur as a multifunctional soil amendment to enhance plant performance as part of nanoenabled agriculture.


Subject(s)
Nanoparticles , Solanum lycopersicum , Sulfur , Solanum lycopersicum/metabolism , Solanum lycopersicum/drug effects , Sulfur/metabolism , Sulfur/chemistry , Nanoparticles/chemistry , Nanoparticles/metabolism , Photosynthesis , Surface Properties , Time Factors , Fertilizers , Stearic Acids/metabolism , Stearic Acids/chemistry , Plant Leaves/metabolism
4.
Food Res Int ; 184: 114213, 2024 May.
Article in English | MEDLINE | ID: mdl-38609212

ABSTRACT

Understanding the impact of minor components and the fatty acid profile of oil on oleogel properties is essential for optimizing their characteristics. Considering the scarcity of literature addressing this aspect, this study aimed to explore the correlation between these factors and the properties of beeswax and stearic acid-based oleogels derived from rice bran oil and sesame oil. Minor oil components were modified by stripping the oil, heating the oil with water, and adding ß-sitosterol. Oleogels were then prepared using a mixture of beeswax and stearic acid (3:1, w/w) at a concentration of 11.74 % (w/w). The properties of oils and oleogels were evaluated. The findings indicated that minor components and fatty acid composition of the oils substantially influence the oleogel properties. Removing minor components by stripping resulted in smaller and less uniformly distributed crystals and less oil binding capacity compared to the oleogels prepared from untreated oils. A moderate amount of minor components exhibited a significant influence on oleogel properties. The addition of ß-sitosterol did not show any influence on oleogel properties except for the oleogel made from untreated oil blend added with ß-sitosterol which had more uniform crystals in the microstructure and demonstrated better rheological stability when stored at 5 °C for two months. The oil composition did not show any influence on the thermal and molecular properties of oleogels. Consequently, the oleogel formulation derived from the untreated oil blend enriched with ß-sitosterol was identified as the optimal formula for subsequent development. The findings of this study suggest that the physical and mechanical properties as well as the oxidative stability of beeswax and stearic acid-based oleogels are significantly affected by the minor constituents and fatty acid composition of the oil. Moreover, it demonstrates that the properties of oleogels can be tailored by modifying oil composition by blending different oils.


Subject(s)
Fatty Acids , Stearic Acids , Waxes , Rice Bran Oil , Organic Chemicals
5.
Microbiol Spectr ; 12(5): e0050824, 2024 May 02.
Article in English | MEDLINE | ID: mdl-38501867

ABSTRACT

Tuberculostearic acid (TBSA) is a fatty acid unique to mycobacteria and some corynebacteria and has been studied due to its diagnostic value, biofuel properties, and role in membrane dynamics. In this study, we demonstrate that TBSA production can be abrogated either by addition of pivalic acid to mycobacterial growth cultures or by a bfaA gene knockout encoding a flavin adenine dinucleotide (FAD)-binding oxidoreductase. Mycobacterium avium subspecies paratuberculosis (Map) growth and TBSA production were inhibited in 0.5-mg/mL pivalic acid-supplemented cultures, but higher concentrations were needed to have a similar effect in other mycobacteria, including Mycobacterium smegmatis. While Map C-type strains, isolated from cattle and other ruminants, will produce TBSA in the absence of pivalic acid, the S-type Map strains, typically isolated from sheep, do not produce TBSA in any condition. A SAM-dependent methyltransferase encoded by bfaB and FAD-binding oxidoreductase are both required in the two-step biosynthesis of TBSA. However, S-type strains contain a single-nucleotide polymorphism in the bfaA gene, rendering the oxidoreductase enzyme vestigial. This results in the production of an intermediate, termed 10-methylene stearate, which is detected only in S-type strains. Fatty acid methyl ester analysis of a C-type Map bfaA knockout revealed the loss of TBSA production, but the intermediate was present, similar to the S-type strains. Collectively, these results demonstrate the subtle biochemical differences between two primary genetic lineages of Map and other mycobacteria as well as explain the resulting phenotype at the genetic level. These data also suggest that TBSA should not be used as a diagnostic marker for Map.IMPORTANCEBranched-chain fatty acids are a predominant cell wall component among species belonging to the Mycobacterium genus. One of these is TBSA, which is a long-chain middle-branched fatty acid used as a diagnostic marker for Mycobacterium tuberculosis. This fatty acid is also an excellent biolubricant. Control of its production is important for industrial purposes as well as understanding the biology of mycobacteria. In this study, we discovered that a carboxylic acid compound termed pivalic acid inhibits TBSA production in mycobacteria. Furthermore, Map strains from two separate genetic lineages (C-type and S-type) showed differential production of TBSA. Cattle-type strains of Mycobacterium avium subspecies paratuberculosis produce TBSA, while the sheep-type strains do not. This important phenotypic difference is attributed to a single-nucleotide deletion in sheep-type strains of Map. This work sheds further light on the mechanism used by mycobacteria to produce tuberculostearic acid.


Subject(s)
Bacterial Proteins , Mycobacterium avium subsp. paratuberculosis , Paratuberculosis , Stearic Acids , Mycobacterium avium subsp. paratuberculosis/genetics , Mycobacterium avium subsp. paratuberculosis/metabolism , Mycobacterium avium subsp. paratuberculosis/drug effects , Animals , Paratuberculosis/microbiology , Cattle , Bacterial Proteins/genetics , Bacterial Proteins/metabolism , Sheep/microbiology , Fatty Acids/metabolism , Polymorphism, Single Nucleotide , Methyltransferases/genetics , Methyltransferases/metabolism
6.
Cryo Letters ; 45(1): 28-35, 2024.
Article in English | MEDLINE | ID: mdl-38538369

ABSTRACT

BACKGROUND: Intracellular lipids are sensitive to freezing. Lipidome modification is an important tool for studying the role of intracellular lipids in cryotolerance of mammalian oocytes and preimplantation embryos. OBJECTIVE: To study the effects of in vitro exposure of murine embryos to saturated stearic acid (SA) on the lipid content, embryo development and cryotolerance. MATERIALS AND METHODS: In vivo derived mouse embryos were cultured with 100 uM SA for 48 h up to the morula/blastocyst stage. Some of the SA-treated embryos were chosen for the evaluation of their development competence and the change in the lipidome, and other embryos were either slowly frozen or rapidly vitrified. RESULTS: Nile red staining combined with confocal laser scanning microscopy revealed a decrease in the total amount of lipids in the SA-treated embryos. Raman measurements showed that the lipid unsaturation was lower in embryos after in vitro SA culture. The addition of SA did not affect the embryo development before cryopreservation, but negatively affected the results of slow freezing cryopreservation and vitrification. CONCLUSION: In vitro SA exposure lowered the total amount of intracellular lipids and unsaturation in mouse embryos. The changes were accompanied with a significantly lower efficacy of embryo cryopreservation. https://doi.org/10.54680/fr24110110512.


Subject(s)
Cryopreservation , Stearic Acids , Vitrification , Animals , Mice , Cryopreservation/methods , Embryo, Mammalian , Blastocyst , Embryonic Development , Lipids , Embryo Culture Techniques , Mammals
7.
Int J Pharm ; 654: 123930, 2024 Apr 10.
Article in English | MEDLINE | ID: mdl-38387820

ABSTRACT

Ginsenoside F1 (GF1) is a potential drug candidate for the treatment of Alzheimer's disease. Nevertheless, its low oral bioavailability and poor solubility limit clinical application. By utilizing either a direct or indirect approach, intranasal administration is a non-invasive drug delivery method that can deliver drugs to the brain rapidly. But large molecule drug delivered to the brain through intranasal administration may be insufficient to reach required concentration for therapeutic effect. In this study, using GF1 as a model drug, the feasibility of intranasal administration in combination with absorption enhancers to increase brain distribution of GF1 was explored. First of all, the appropriate absorption enhancers were screened by in situ nasal perfusion study. GF1-HP-ß-CD inclusion complex was prepared and characterized. Thereafter, in vivo absorption of GF1 after intranasal or intravenous administration of its inclusion complex with/without absorption enhancers was investigated, and safety of the formulations was evaluated. The results showed that 2% Solutol HS 15 was a superior absorption enhancer. HP-ß-CD inclusion complex improved GF1 solubility by 150 fold. Following intranasal delivery, the absolute bioavailability of inclusion complex was 46%, with drug brain targeting index (DTI) 247% and nose-to-brain direct transport percentage (DTP) 58%. Upon further addition of 2% Solutol HS 15, the absolute bioavailability was increased to 75%, with DTI 315% and DTP 66%. Both nasal cilia movement and biochemical substances (total protein and lactate dehydrogenase) leaching studies demonstrated 2% Solutol HS 15 was safe to the nasal mucosa. In conclusion, intranasal administration combining with safe absorption enhancers is an effective strategy to enhance drug distribution in the brain, showing promise for treating disorders related to the central nervous system.


Subject(s)
Brain , Ginsenosides , Nasal Mucosa , Polyethylene Glycols , Stearic Acids , Administration, Intranasal , 2-Hydroxypropyl-beta-cyclodextrin , Brain/metabolism , Nasal Mucosa/metabolism , Drug Delivery Systems/methods
8.
CNS Neurosci Ther ; 30(2): e14594, 2024 02.
Article in English | MEDLINE | ID: mdl-38332538

ABSTRACT

BACKGROUND: With the rapidly increasing prevalence of metabolic diseases such as type 2 diabetes mellitus (T2DM), neuronal complications associated with these diseases have resulted in significant burdens on healthcare systems. Meanwhile, effective therapies have remained insufficient. A novel fatty acid called S-9-PAHSA has been reported to provide metabolic benefits in T2DM by regulating glucose metabolism. However, whether S-9-PAHSA has a neuroprotective effect in mouse models of T2DM remains unclear. METHODS: This in vivo study in mice fed a high-fat diet (HFD) for 5 months used fasting blood glucose, glucose tolerance, and insulin tolerance tests to examine the effect of S-9-PAHSA on glucose metabolism. The Morris water maze test was also used to assess the impact of S-9-PAHSA on cognition in the mice, while the neuroprotective effect of S-9-PAHSA was evaluated by measuring the expression of proteins related to apoptosis and oxidative stress. In addition, an in vitro study in PC12 cells assessed apoptosis, oxidative stress, and mitochondrial membrane potential with or without CAIII knockdown to determine the role of CAIII in the neuroprotective effect of S-9-PAHSA. RESULTS: S-9-PAHSA reduced fasting blood glucose levels significantly, increased insulin sensitivity in the HFD mice and also suppressed apoptosis and oxidative stress in the cortex of the mice and PC12 cells in a diabetic setting. By suppressing oxidative stress and apoptosis, S-9-PAHSA protected both neuronal cells and microvascular endothelial cells in in vivo and in vitro diabetic environments. Interestingly, this protective effect of S-9-PAHSA was reduced significantly when CAIII was knocked down in the PC12 cells, suggesting that CAIII has a major role in the neuroprotective effect of S-9-PAHSA. However, overexpression of CAIII did not significantly enhance the protective effect of S-9-PAHSA. CONCLUSION: S-9-PAHSA mediated by CAIII has the potential to exert a neuroprotective effect by suppressing apoptosis and oxidative stress in neuronal cells exposed to diabetic conditions. Furthermore, S-9-PAHSA has the capability to reduce fasting blood glucose and LDL levels and enhance insulin sensitivity in mice fed with HFD.


Subject(s)
Diabetes Mellitus, Type 2 , Insulin Resistance , Neuroprotective Agents , Palmitic Acid , Stearic Acids , Animals , Mice , Rats , Apoptosis , Blood Glucose/metabolism , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/drug therapy , Diet, High-Fat/adverse effects , Disease Models, Animal , Endothelial Cells/metabolism , Neuroprotective Agents/pharmacology , Neuroprotective Agents/therapeutic use , Oxidative Stress , Carbonic Anhydrase III/drug effects , Carbonic Anhydrase III/metabolism
9.
Int J Mol Sci ; 25(3)2024 Jan 30.
Article in English | MEDLINE | ID: mdl-38338979

ABSTRACT

Oil palm, a tropical woody oil crop, is widely used in food, cosmetics, and pharmaceuticals due to its high production efficiency and economic value. Palm oil is rich in free fatty acids, polyphenols, vitamin E, and other nutrients, which are beneficial for human health when consumed appropriately. Therefore, investigating the dynamic changes in free fatty acid content at different stages of development and hypothesizing the influence of regulatory genes on free fatty acid metabolism is crucial for improving palm oil quality and accelerating industry growth. LC-MS/MS is used to analyze the composition and content of free fatty acids in the flesh after 95 days (MS1 and MT1), 125 days (MS2 and MT2), and 185 days (MS3 and MT3) of Seedless (MS) and Tenera (MT) oil palm species fruit pollination. RNA-Seq was used to analyze the expression of genes regulating free fatty acid synthesis and accumulation, with differences in genes and metabolites mapped to the KEGG pathway map using the KEGG (Kyoto encyclopedia of genes and genomes) enrichment analysis method. A metabolomics study identified 17 types of saturated and 13 types of unsaturated free fatty acids during the development of MS and MT. Transcriptomic research revealed that 10,804 significantly different expression genes were acquired in the set differential gene threshold between MS and MT. The results showed that FabB was positively correlated with the contents of three main free fatty acids (stearic acid, myristate acid, and palmitic acid) and negatively correlated with the contents of free palmitic acid in the flesh of MS and MT. ACSL and FATB were positively correlated with the contents of three main free fatty acids and negatively correlated with free myristate acid. The study reveals that the expression of key enzyme genes, FabB and FabF, may improve the synthesis of free myristate in oil palm flesh, while FabF, ACSL, and FATB genes may facilitate the production of free palmitoleic acid. These genes may also promote the synthesis of free stearic acid and palmitoleic acid in oil palm flesh. However, the FabB gene may inhibit stearic acid synthesis, while ACSL and FATB genes may hinder myristate acid production. This study provides a theoretical basis for improving palm oil quality.


Subject(s)
Arecaceae , Fatty Acids, Nonesterified , Humans , Fatty Acids, Nonesterified/metabolism , Fatty Acids/metabolism , Palm Oil , Chromatography, Liquid , Myristates/metabolism , Arecaceae/genetics , Arecaceae/metabolism , Tandem Mass Spectrometry , Fatty Acids, Unsaturated/metabolism , Palmitic Acid/metabolism , Gene Expression Profiling , Stearic Acids/metabolism , Plant Oils/metabolism
10.
Int J Pharm ; 651: 123792, 2024 Feb 15.
Article in English | MEDLINE | ID: mdl-38190952

ABSTRACT

The majority of tablets manufactured contain lubricants to reduce friction during ejection. However, especially for plastically deforming materials, e.g., microcrystalline cellulose (MCC), the internal addition of lubricants is known to reduce tablet tensile strength. This reduction is caused by the surface coverage by lubricant particles, the extent of which depends on both process and formulation parameters. Previously published models to predict the lubrication effect on mechanical strength do not account for changes in the excipient particle size. In this study, the impact of both lubricant concentration and mixing time on the tensile strength of tablets consisting of three different grades of MCC and four grades of magnesium stearate (MgSt) was evaluated. By taking into account the particle size of the applied excipients, a unifying relationship between the theoretically estimated surface coverage and compactibility reduction was identified. Evaluating the dispersion kinetics of MgSt as a function of time reveals a substantial impact of the initial surface coverage on the dispersion rate, while the minimal tensile strength was found to be comparable for the majority of formulations. In summary, the presented work extends the knowledge of lubricant dispersion and facilitates the reduction of necessary experiments during the development of new tablet formulations.


Subject(s)
Cellulose , Excipients , Stearic Acids , Particle Size , Excipients/chemistry , Stearic Acids/chemistry , Tablets/chemistry , Lubricants/chemistry , Tensile Strength
11.
Drug Res (Stuttg) ; 74(2): 60-66, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38286420

ABSTRACT

Parkinson's disease is the highest prevalent neurodegenerative disease in elderly individuals after Alzheimer's disease. The pathological identification for Parkinson's disease is loss of dopaminergic neurons in substantia nigra region of the brain that in turn leads to dopamine deficiency that affects the body's normal physiological and neurological disorder. The important drawback in the modality of treatment is levodopa is only supplying depleted dopamine in the brain, it does not affect neurodegeneration. Even though levodopa manages the disease, an alternative treatment strategy is required to stop or prevent further degeneration of neuron. The compound with neuroprotector activity suits the requirement. Of them, stearic acid plays a vital role in protecting neurons against oxidative stress through a Phosphoinositide 3-kinase-dependent mechanism. Hence, our present study aimed to design, synthesize, and characterize the levodopa stearic acid hydrazide conjugate. Additionally, evaluate the cytotoxicity of synthesized compound in SHSY5Y: cell lines. In brief, levodopa was conjugated to the stearic acid successfully and was confirmed with Fourier-transform infrared spectroscopy, Nuclear magnetic resonance, and Mass Spectroscopy. In vitro cell viability study in SHSY5Y: cell lines showed elevated cell viability in 0.134 µm concentration of Conjugate, and 0.563 µm concentration of levodopa. Showing that the synthesized compound could offer an improved treatment strategy for Parkinson's disease.


Subject(s)
Neurodegenerative Diseases , Parkinson Disease , Stearic Acids , Humans , Aged , Parkinson Disease/drug therapy , Parkinson Disease/pathology , Levodopa/pharmacology , Levodopa/metabolism , Dopamine/metabolism , Phosphatidylinositol 3-Kinases/metabolism , Dopaminergic Neurons , Antiparkinson Agents/pharmacology , Antiparkinson Agents/therapeutic use , Antiparkinson Agents/metabolism
12.
J Dairy Sci ; 107(1): 278-287, 2024 Jan.
Article in English | MEDLINE | ID: mdl-37690714

ABSTRACT

We determined the effects of altering the ratio of palmitic (C16:0) and stearic (C18:0) acids in supplemental fatty acid (FA) blends on production responses of mid-lactation dairy cows. Twenty-four multiparous Holstein cows (mean ± standard deviation; 47.1 ± 5.8 kg of milk yield, 109 ± 23 DIM) were randomly assigned to treatment sequences in a replicated 4 × 4 Latin square design with 21-d periods. Treatments were a control diet not supplemented with FA (CON), and 3 diets incorporating 1.5% of dry matter (DM) FA supplement blends containing 30% C16:0 + 50% C18:0, 50% C16:0 + 30% C18:0, and 80% C16:0 + 10% C18:0. Additionally, the FA blends were balanced to contain 10% of oleic acid (cis-9 C18:1). The FA blends replaced soyhulls in the CON diet. Diets were formulated to contain (% of DM) 31.0% neutral detergent fiber, 27.0% starch, and 16.9% crude protein. The statistical model included the random effect of cow within square and the fixed effects of period, treatment, and their interaction. Preplanned contrasts included CON versus overall effect of FA supplementation and the linear and quadratic effects of increasing C16:0 in FA blends. Overall FA treatment had no effect on dry matter intake (DMI), but increasing C16:0 linearly increased DMI. Compared with CON, overall FA treatment increased yields of milk, 3.5% of fat-corrected milk, energy-corrected milk, and milk fat but did not affect milk protein yield. Increasing C16:0 linearly increased milk fat yield and tended to linearly increase the yields of 3.5% of fat-corrected milk and energy-corrected milk. Fatty acid supplementation decreased the yield of de novo milk FA but increased yields of mixed and preformed milk FA compared with CON. Increasing C16:0 in FA treatments did not affect the yield of de novo milk FA, linearly increased the yield of mixed, and decreased the yield of preformed milk FA. In summary, feeding FA supplements containing C16:0 and C18:0 increased milk production responses with no effect on DMI compared with a control diet. Mid-lactation cows producing ∼40 to 50 kg/d milk yield responded best to increasing supplemental C16:0 in FA supplements, demonstrating that FA supplements higher in C16:0 and limited in C18:0 improves production responses.


Subject(s)
Fatty Acids , Palmitic Acid , Female , Cattle , Animals , Fatty Acids/metabolism , Digestion , Animal Feed/analysis , Lactation/physiology , Diet/veterinary , Dietary Supplements , Stearic Acids/pharmacology
13.
Int J Pharm ; 649: 123636, 2024 Jan 05.
Article in English | MEDLINE | ID: mdl-38013042

ABSTRACT

External lubrication of tooling with magnesium stearate (MgSt) is a common strategy to eliminate punch sticking when compressing powders with a high sticking propensity, such as many pure active pharmaceutical ingredients (APIs). We found that it actually led to aggravated punch sticking at low compaction pressures. This counterintuitive phenomenon was explained based on interplay of forces among the punch tip, MgSt, and API. The explanation is supported by the observed effects of pressure and mechanical properties of APIs on this phenomenon.


Subject(s)
Stearic Acids , Drug Compounding , Tablets , Lubrication
14.
Eur J Pharm Biopharm ; 193: 262-273, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37944711

ABSTRACT

This study discusses the lubricant properties of magnesium stearate solid lipid nanoparticles (MgSt-SLN) and their effect on the tabletability, mechanical properties, disintegration, and acetaminophen-model dissolution time of microcrystalline cellulose (MCC) tablets prepared by direct compression. The behavior of MgSt-SLN was compared to reference material (RM) to identify advantages and drawbacks. The nanoprecipitation/ion exchange method was employed to prepare the MgSt-SLN. Particle size, zeta potential, specific surface area, morphology, and true density were measured to characterize the nanosystem. The MgSt-SLN particle sizes obtained were 240 ± 5 nm with a specific surface area of 12.2 m2/g. The MCC tablets with MgSt-SLN presented a reduction greater than 20 % in their ejection force, good tabletability, higher tensile strength, lower disintegration delay, and marked differences in acetaminophen dissolution when compared to the RM. The reduced particle size of the magnesium stearate seems to offer a promising technological advantage as an efficient lubricant process that does not affect the properties of tablets.


Subject(s)
Acetaminophen , Lubricants , Lubricants/chemistry , Stearic Acids/chemistry , Excipients/chemistry , Tablets/chemistry , Tensile Strength
15.
Pharm Dev Technol ; 28(10): 992-999, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37938090

ABSTRACT

Punch sticking is a recurrent problem during the pharmaceutical tableting process. Powder moisture content plays a key role in the buildup of sticking; it evaporates due to increased tablet temperature, accumulates at the punch-tablet interface, and causes sticking through capillary force. This study investigated the effects of compaction pressure (CP), compaction speed (CS), and lubrication level (magnesium stearate (MgSt) ratio) on tablet surface temperature (TST) and tablet surface moisture content (TSMC). TST and TSMC were measured with an infrared thermal camera and near-infrared sensor, respectively. Microcrystalline cellulose was used as the tableting powder and MgSt as the lubricant. The low range of CS values (16-32 mm/s) considered in this study did not have significant effects on TST and TSMC. MgSt ratio had a significant positive effect on TST; this may be explained by the increase in powder blend effusivity with the addition of MgSt. However, MgSt ratio did not have a significant effect on TSMC. CP had a significant positive effect on both TST and TSMC. Increased CP induced higher heat generation through particle deformation and friction during the compaction phase, leading to increased TST. Furthermore, the water vapor diffusion rate through the powder bed might have increased due to the rise in thermal energy and led to further moisture accumulation at the tablet-punch interface, causing the significant positive effect of CP on TSMC. This result may explain the occurrence of sticking regardless of the CP applied during the tableting process.


Subject(s)
Lubricants , Stearic Acids , Lubrication , Powders/chemistry , Temperature , Lubricants/chemistry , Tablets/chemistry , Stearic Acids/chemistry
16.
Int J Biol Macromol ; 253(Pt 8): 127324, 2023 Dec 31.
Article in English | MEDLINE | ID: mdl-37838116

ABSTRACT

Stearic acid (C18:0, SA) is a saturated long-chain fatty acid (LCFA) that has a prominent function in lactating dairy cows. It is obtained primarily from the diet and is stored in the form of triacylglycerol (TAG) molecules. The transmembrane glycoprotein cluster of differentiation 36 (CD36) is also known as fatty acid translocase, but whether SA promotes lipid synthesis through CD36 and FAK/mTORC1 signaling is unknown. In this study, we examined the function and mechanism of CD36-mediated SA-induced lipid synthesis in bovine mammary epithelial cells (BMECs). SA-enriched supplements enhanced lipid synthesis and the FAK/mTORC1 pathway in BMECs. SA-induced lipid synthesis, FAK/mTORC1 signaling, and the expression of lipogenic genes were impaired by anti-CD36 and the CD36-specific inhibitor SSO, whereas overexpression of CD36 effected the opposite results. Inhibition of FAK/mTORC1 by TAE226/Rapamycin attenuated SA-induced TAG synthesis, inactivated FAK/mTORC1 signaling, and downregulated the lipogenic genes PPARG, CD36, ACSL1, SCD, GPAT4, LIPIN1, and DGAT1 at the mRNA and protein levels in BMECs. By coimmunoprecipitation and yeast two-hybrid screen, CD36 interacted directly with Fyn but not Lyn, and Fyn bound directly to FAK; FAK also interacted directly with TSC2. CD36 linked FAK through Fyn, and FAK coupled mTORC1 through TSC2 to form the CD36/Fyn/FAK/mTORC1 signaling axis. Thus, stearic acid promotes lipogenesis through CD36 and Fyn/FAK/mTORC1 signaling in BMECs. Our findings provide novel insights into the underlying molecular mechanisms by which LCFA supplements promote lipid synthesis in BMECs.


Subject(s)
Lactation , Lipogenesis , Female , Cattle , Animals , Lipogenesis/genetics , Mechanistic Target of Rapamycin Complex 1/metabolism , Mammary Glands, Animal/metabolism , Stearic Acids/pharmacology , Fatty Acids/metabolism , Epithelial Cells/metabolism
17.
Front Biosci (Landmark Ed) ; 28(8): 181, 2023 08 28.
Article in English | MEDLINE | ID: mdl-37664932

ABSTRACT

BACKGROUND: A long-term consumption of saturated fat significantly increases the concentration of saturated fatty acids in serum, which accelerates the appearance of senescence markers in ß-cells and leads to their dysfunction. An understanding of the mechanisms underlying ß-cell senescence induced by stearic acid and the exploration of effective agents preventing it remains largely unclear. Here, we aimed to investigate the protective effect of metformin against stearic acid-treated ß-cell senescence and to assess the involvement of miR-297b-5p in this process. METHODS: To identify senescence, we measured senescence-associated ß-galactosidase activity and the expression of senescence-related genes. Gain and loss of function approaches were applied to explore the role of miR-297b-5p in stearic acid-induced ß-cell senescence. Bioinformatics analysis and a luciferase activity assay were used to predict the downstream targets of miR-297b-5p. RESULTS: Stearic acid markedly induced senescence and suppressed miR-297b-5p expression in mouse ß-TC6 cells, which were significantly alleviated by metformin. After transfection of miR-297b-5p mimics, stearic acid-evoked ß-cell senescence was remarkably prevented. Insulin-like growth factor-1 receptor was identified as a direct target of miR-297b-5p. Inhibition of the insulin-like growth factor-1 receptor prevented stearic acid-induced ß-cell senescence and dysfunction. Moreover, metformin alleviates the impairment of the miR-297b-5p inhibitor in ß-TC6 cells. Additionally, long-term consumption of a high-stearic-acid diet significantly increased senescence and reduced miR-297b-5p expression in mouse islets. CONCLUSIONS: These findings imply that metformin alleviates ß-cell senescence by stearic acid through upregulating miR-297b-5p to suppress insulin-like growth factor-1 receptor expression, thereby providing a potential target to not only prevent high fat-diet-induced ß-cell dysfunction but also for metformin therapy in type 2 diabetes.


Subject(s)
Diabetes Mellitus, Type 2 , Insulin-Secreting Cells , Metformin , MicroRNAs , Receptor, IGF Type 1 , Animals , Mice , Insulin-Like Growth Factor I , Metformin/pharmacology , MicroRNAs/genetics , Stearic Acids/pharmacology , Receptor, IGF Type 1/genetics
18.
Pharm Res ; 40(10): 2479-2492, 2023 Oct.
Article in English | MEDLINE | ID: mdl-37752367

ABSTRACT

INTRODUCTION: Tablets are commonly produced by internally adding particulate lubricants, which are known to possibly lower the mechanical strength of tablets. This reduction is caused by the coverage of matrix forming components by lubricant particles, resulting in decreased interparticulate interactions. The known incompatibilities with some active compounds of the predominantly used lubricant, magnesium stearate, call for the in-depth characterization of alternative lubricants. PURPOSE: Investigation of the dispersion behavior of five commonly applied pharmaceutical lubricants by mathematically modeling the dispersion kinetics for short and extended mixing times. METHODS: The dispersion behavior of five different pharmaceutical lubricants were examined by systematically varying lubricant concentration and mixing time of binary formulations and evaluating the kinetic of tensile strength reduction by theoretically estimating the surface coverage based on particle sizes. RESULTS: For short mixing times, a unifying relationship between compactibility reduction and theoretical surface coverage was identified. Subsequently, for extended mixing times, distinct differences in the shear strength and dispersion kinetics of the investigated lubricants were found. CONCLUSIONS: The lubricant particle size controls the tensile strength reduction if short mixing times are applied. For extended mixing times, the investigated lubricants can be divided into two groups in terms of dispersion kinetics. Possible underlying reasons are discussed in detail in order to enhance the general understanding of lubricant dispersions in tablet formulations.


Subject(s)
Lubricants , Stearic Acids , Drug Compounding , Tensile Strength , Excipients , Tablets
19.
Sci Rep ; 13(1): 16482, 2023 09 30.
Article in English | MEDLINE | ID: mdl-37777517

ABSTRACT

This study evaluated the interaction effects of irrigation level (well-watered and water stress conditions) and inoculation by different mycorrhizal species (non-inoculated, Funneliformis mosseae, Rhizophagus irregularis, Claroideoglomus claroideum, and Glomus fasciculatum) on mycorrhizal colonization, antioxidant activity, seed yield and oil quality of two sesame cultivars (Yekta and Naz). Water deficit decreased mycorrhizal colonization, seed yield and oil concentration but increased antioxidant activity and seed total phenol and flavonoid concentrations. However, mycorrhizal inoculation increased antioxidant activity, seed yield, oil concentration and total phenolic and flavonoids. The lowest reduction by water stress and the highest increase by inoculation in seed yield were observed in Naz plants inoculated by Cl. claroideum. Principal component analysis showed the highest differentiation effect of water stress compared to mycorrhizal inoculation on both cultivars, indicating the relative sensitivity of the two cultivars to water deficit. However, the application of different species of mycorrhizal fungi versus the non-inoculation conditions was somewhat discriminative. In terms of fatty acids, in most cases, water stress increased oleic, palmitic and stearic acids and decreased linoleic and linolenic acids but inoculation increased oleic and linoleic acids and decreased linolenic, palmitic and stearic acids. Regarding phenolic and flavonoids components, the contents of chlorogenic and caffeic acids were increased by water stress but no consistent trend was noted in response to water stress for the other compounds. Mycorrhizal inoculation generally decreased chlorogenic acid but increased gallic, caffeic, p-coumaric, and ferulic acids. In conclusion, the results of the present study may help to increase the level of valuable compounds in sesame for further pharmaceutical purposes under water stress conditions and mycorrhizal symbiosis.


Subject(s)
Mycorrhizae , Sesamum , Mycorrhizae/physiology , Antioxidants/pharmacology , Plant Roots/microbiology , Fatty Acids/pharmacology , Dehydration , Phenols/pharmacology , Seeds , Flavonoids/pharmacology , Stearic Acids/pharmacology
20.
Arq Bras Cardiol ; 120(8): e20220598, 2023.
Article in English, Portuguese | MEDLINE | ID: mdl-37672472

ABSTRACT

BACKGROUND: Several studies have associated dietary saturated fatty acids (SFAs) with cardiovascular risk but there are still many controversies. Most of these studies have focused on the effects of palmitic acid on circulating lipids. Stearic acid usually shows a neutral effect on blood lipids, however, there is a lack of clinical studies assessing the link with inflammatory and endothelial dysfunction markers. OBJECTIVE: To evaluate the association of red blood cell (RBC) SFA (palmitic and stearic acids) with circulating inflammatory and endothelial dysfunction biomarkers. METHODS: Cross-sectional study of 79 adults of both sexes with at least one cardiovascular risk factor but without previous events (acute myocardial infarction or stroke). Plasma biomarkers - lipids, glucometabolic markers, high-sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6), interleukin-10 (IL-10), monocyte chemoattractant protein-1 (MCP-1), and tumor necrosis factor-α (TNF-α) - and RBC palmitic and stearic fatty acids were analyzed. The associations were assessed by correlation and multiple linear regression analyses, with statistical significance set at p < 0.05. RESULTS: Palmitic acid showed no significant associations with traditional cardiovascular risk factors or inflammatory markers. Stearic acid, on the other hand, was inversely correlated with blood cholesterol and triglycerides, but independently associated with hs-CRP, IL-6, and TNF-α. CONCLUSION: Stearic acid is associated with inflammatory and endothelial dysfunction biomarkers in individuals with at least one cardiovascular risk factor.


FUNDAMENTO: Vários estudos têm associado o consumo de ácidos graxos saturados (AGSs) com risco cardiovascular, mas ainda existem muitas controvérsias. A maioria desses estudos avaliou os efeitos do ácido palmítico sobre lipídios circulantes. O ácido esteárico geralmente apresenta um efeito neutro sobre os lipídios sanguíneos, mas faltam estudos clínicos avaliando sua relação com marcadores de inflamação e de disfunção endotelial. OBJETIVOS: Avaliar a associação de AGSs das hemácias (ácido palmítico e ácido esteárico) com biomarcadores inflamatórios e de disfunção endotelial circulantes. MÉTODOS: Estudo transversal que incluiu 79 adultos de ambos os sexos com pelo menos um fator de risco cardiovascular, mas sem eventos prévios (infarto agudo do miocárdio ou acidente vascular cerebral). Biomarcadores plasmáticos ­ lipídios, marcadores glicometabólicos, proteína C ultrassensível (PCR-us), Interleucina 6 (IL-6), Interleucina 10 (IL-10), Fator de Necrose Tumoral-α (TNF-α), Proteína quimioatraente de Monócitos 1 (MCP-1) ­ e ácidos graxos das hemácias (ácidos palmítico e esteárico) foram analisados. As associações foram avaliadas por análises de correlações e regressões lineares múltiplas, com significância estatística estabelecida em p<0,05. RESULTADOS: O ácido palmítico não apresentou associações com fatores de risco cardiovasculares ou com marcadores inflamatórios. Por outro lado, o ácido esteárico foi inversamente correlacionado com PCR-us, IL-6 e TNF-α, mas independentemente associado com PCR-us, IL-6, e TNF-α. CONCLUSÃO: O ácido esteárico está associado com biomarcadores inflamatórios e disfunção endotelial em indivíduos com um ou mais fatores de risco cardiovascular.


Subject(s)
Cardiovascular Diseases , Stroke , Adult , Female , Male , Humans , Palmitic Acid , C-Reactive Protein , Cardiovascular Diseases/etiology , Cross-Sectional Studies , Interleukin-6 , Tumor Necrosis Factor-alpha , Risk Factors , Stearic Acids , Biomarkers , Heart Disease Risk Factors
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