-
International Journal of Molecular... May 2024The modified release of active substances such as chlorzoxazone from matrix tablets, based on KollidonSR and chitosan, depends both on the drug solubility in the...
The modified release of active substances such as chlorzoxazone from matrix tablets, based on KollidonSR and chitosan, depends both on the drug solubility in the dissolution medium and on the matrix composition. The aim of this study is to obtain some new oral matrix tablet formulations, based on KollidonSR and chitosan, in order to optimize the low-dose oral bioavailability of chlorzoxazone, a non-steroidal anti-inflammatory drug of class II Biopharmaceutical Classification System. Nine types of chlorzoxazone matrix tablets were obtained using the direct compression method by varying the components ratio as 1:1, 1:2, and 1:3 chlorzoxazone/excipients, 20-40 w/w % KollidonSR, 3-7 w/w % chitosan while the auxiliary substances: Aerosil 1 w/w %, magnesium stearate 0.5 w/w % and Avicel up to 100 w/w % were kept in constant concentrations. Pharmaco-technical characterization of the tablets included the analysis of flowability and compressibility properties (flow time, friction coefficient, angle of repose, Hausner ratio, and Carr index), and pharmaco-chemical characteristics (such as mass and dose uniformity, thickness, diameter, mechanical strength, friability, softening degree, and in vitro release profiles). Based on the obtained results, only three matrix tablet formulations (F1b, F2b, and F3b, containing 30 w/w % KOL and 5 w/w % CHT, were selected and further tested. These formulations were studied in detail by Fourier-transform infrared spectrometry, X-ray diffraction, thermogravimetry, and differential scanning calorimetry. The three formulations were comparatively studied regarding the release kinetics of active substances using in vitro release testing. The results were analyzed by fitting into four representative mathematical models for the modified-release oral formulations. In vitro kinetic study revealed a complex mechanism of release occurring in two steps of drug release, the first step (0-2 h) and the second (2-36 h). Two factors were calculated to assess the release profile of chlorzoxazone: f1-the similarity factor, and f2-the factor difference. The results have shown that both KollidonSR and chitosan may be used as matrix-forming agents when combined with chlorzoxazone. The three formulations showed optima pharmaco-technical properties and in vitro kinetic behavior; therefore, they have tremendous potential to be used in oral pharmaceutical products for the controlled delivery of chlorzoxazone. In vitro dissolution tests revealed a faster drug release for the F2b sample.
Topics: Tablets; Chlorzoxazone; Delayed-Action Preparations; Chitosan; Hydrophobic and Hydrophilic Interactions; Drug Liberation; Solubility; Excipients; Chemistry, Pharmaceutical
PubMed: 38791175
DOI: 10.3390/ijms25105137 -
Heliyon May 2024Docosahexaenoic acid (DHA, C22:6 n-3), an omega-3 polyunsaturated fatty acid, offers several beneficial effects. DHA helps in reducing depression, autoimmune diseases,... (Review)
Review
Docosahexaenoic acid (DHA, C22:6 n-3), an omega-3 polyunsaturated fatty acid, offers several beneficial effects. DHA helps in reducing depression, autoimmune diseases, rheumatoid arthritis, attention deficit hyperactivity syndrome, and cardiovascular diseases. It can stimulate the development of brain and nerve, alleviate lipids metabolism-related disorders, and enhance vision development. However, DHA susceptibility to chemical oxidation, poor water solubility, and unpleasant order could restrict its applications for nutritional and therapeutic purposes. To avoid these drawbacks and enhance its bioavailability, DHA can be encapsulated using an effective delivery system. Several encapsulation methods are recognized, and DHA-loaded nanoparticles have demonstrated numerous benefits. In clinical studies, positive influences on the development of several diseases have been reported, but some assumptions are conflicting and need more exploration, since DHA has a systemic and not a targeted release at the required level. This might cause the applications of nanoparticles that could allow DHA release at the required level and improve its efficiency, thus resulting in a better controlling of several diseases. In the current review, we focused on researches investigating the formulation and development of DHA-loaded nanoparticles using different delivery systems, including low-density lipoprotein, zinc oxide, silver, zein, and resveratrol-stearate. Silver-DHA nanoparticles presented a typical particle size of 24 nm with an incorporation level of 97.67 %, while the entrapment efficiency of zinc oxide-DHA nanoparticles represented 87.3 %. By using zein/Poly (lactic--glycolic acid) stabilized nanoparticles, DHA's encapsulation level reached 84.6 %. We have also highlighted the characteristics, functionality and medical implementation of these nanoparticles in the treatment of inflammations, brain disorders, diabetes as well as hepatocellular carcinoma.
PubMed: 38774069
DOI: 10.1016/j.heliyon.2024.e30946 -
Biomedicine & Pharmacotherapy =... May 2024Nicotinamide mononucleotide (NMN) and nicotinamide riboside (NR) have received considerable attention as anti-aging and anti-metabolic disease nutraceuticals. However,...
Nicotinamide mononucleotide (NMN) and nicotinamide riboside (NR) have received considerable attention as anti-aging and anti-metabolic disease nutraceuticals. However, few studies have focused on their role in ameliorating hepatic metabolic disturbances. In the present study, the effects of NMN and NR on the liver of mice with nonalcoholic fatty liver disease (NAFLD) were investigated via transcriptome and metabolome analyses. NMN and NR reduced body weight gain, improved glucose homeostasis, regulated plasma lipid levels, and ameliorated liver injury, oxidative stress, and lipid accumulation in mice with HFD-induced NAFLD. Integrated transcriptome and metabolome analyses indicated that NMN and NR altered the biosynthesis of unsaturated fatty acids, arachidonic acid metabolism, and linoleic acid metabolism pathways, increased saturated fatty acid (palmitic acid, stearate, and arachidic acid) content, and increased polyunsaturated fatty acid (linoleic acid and eicosapentaenoic acid) content. Quantitative reverse transcription PCR (qRT-PCR) showed that NMN and NR primarily promoted arachidonic acid and linoleic acid catabolism via cytochrome P450 (CYP450) enzymes. This study established a theoretical foundation for the potential use of NMN and NR in future clinical settings.
PubMed: 38729053
DOI: 10.1016/j.biopha.2024.116701 -
Function (Oxford, England) 2024Global prevalence of hypertension is on the rise, burdening healthcare, especially in developing countries where infectious diseases, such as malaria, are also rampant....
Global prevalence of hypertension is on the rise, burdening healthcare, especially in developing countries where infectious diseases, such as malaria, are also rampant. Whether hypertension could predispose or increase susceptibility to malaria, however, has not been extensively explored. Previously, we reported that hypertension is associated with abnormal red blood cell (RBC) physiology and anemia. Since RBC are target host cells for malarial parasite, , we hypothesized that hypertensive patients with abnormal RBC physiology are at greater risk or susceptibility to infection. To test this hypothesis, normotensive (BPN/3J) and hypertensive (BPH/2J) mice were characterized for their RBC physiology and subsequently infected with (), a murine-specific non-lethal strain. When compared to BPN mice, BPH mice displayed microcytic anemia with RBC highly resistant to osmotic hemolysis. Further, BPH RBC exhibited greater membrane rigidity and an altered lipid composition, as evidenced by higher levels of phospholipids and saturated fatty acid, such as stearate (C18:0), along with lower levels of polyunsaturated fatty acid like arachidonate (C20:4). Moreover, BPH mice had significantly greater circulating Ter119 CD71 reticulocytes, or immature RBC, prone to infection. Upon infection with , BPH mice experienced significant body weight loss accompanied by sustained parasitemia, indices of anemia, and substantial increase in systemic pro-inflammatory mediators, compared to BPN mice, indicating that BPH mice were incompetent to clear infection. Collectively, these data demonstrate that aberrant RBC physiology observed in hypertensive BPH mice contributes to an increased susceptibility to infection and malaria-associated pathology.
Topics: Animals; Malaria; Plasmodium yoelii; Mice; Hypertension; Erythrocytes; Disease Susceptibility; Male; Anemia; Disease Models, Animal; Hemolysis
PubMed: 38706961
DOI: 10.1093/function/zqae009 -
International Journal of Pharmaceutics:... Jun 2024Pathogenic bacteria cause chronic bacterial prostatitis (CBP). CPB is characterized by urinary tract infection and persistence of pathogenic bacteria in prostatic...
Pathogenic bacteria cause chronic bacterial prostatitis (CBP). CPB is characterized by urinary tract infection and persistence of pathogenic bacteria in prostatic secretion. Owing to poor blood supply to the prostate gland and limited drug penetration, CBP treatment is difficult. Transferosomes are ultradeformable vesicles for nanocarrier applications, which have become an important area of nanomedicine. Such carriers are specifically targeted to the pathological area to provide maximum therapeutic efficacy. It consists of a lipid bilayer soybean lecithin phosphatidylcholine (PC), an edge activator Tween 80 with various ratios, and a chloroform/methanol core. Depending on the lipophilicity of the active substance, it can be encapsulated within the core or among the lipid bilayer. Due to their exceptional flexibility, which enables them to squeeze themselves through narrow pores that are significantly smaller than their size, they can be a solution. One formulation (Cipro5 PEG) was selected for further in vitro analysis and was composed of phosphatidylcholine (PC), Tween 80, and polyethylene glycol-6 stearate (PEG-6 stearate) in a ratio of 3:3:1 in a chloroform/methanol mixture (1:2 /v). In vitro, the results showed that PEGylated transferosomes had faster drug release, higher permeation, and increased bioavailability. The transferosomes were quantified with a particle size of 202.59 nm, a zeta potential of-49.38 mV, and a drug entrapment efficiency of 80.05%. The aim of this study was to investigate drug targeting. Therefore, Monoclonal antibody IgG was coupled with Cipro5 PEG, which has specificity and selectivity for conjugated nanoparticles. In vivo, a total of twenty-five adult Wistar rats were obtained and randomly divided into 5 groups, each of 5 rats at random: the control group, blank group, positive control group, Cipro 5PEG group, and Cipro 5PEG coupled with IgG antibody group. The cytokines levels (IL-1β, IL-8, and TNF-α) in the serum were detected by analysis kits. Compared with the control group, treatment with Cipro 5PEG coupled with the IgG antibody could significantly inhibit cytokines, according to histological analysis. Cipro 5PEG, coupled with the IgG antibody group, reduced prostate tissue inflammation. Hence, our results show a promising approach to delivering antibiotics for the targeted therapy of CBP.
PubMed: 38706465
DOI: 10.1016/j.ijpx.2024.100247 -
Materials (Basel, Switzerland) Apr 2024Biodiesel is a mixture of saturated and unsaturated Fatty Acid Methyl Esters (FAMEs) whose composition affects the corrosion behavior of metal containers during storage....
Biodiesel is a mixture of saturated and unsaturated Fatty Acid Methyl Esters (FAMEs) whose composition affects the corrosion behavior of metal containers during storage. This study examines the effect of the C=C bond present in selected FAMEs (Methyl Stearate, Methyl Oleate, and Methyl Linoleate) in aluminum corrosion in the absence of oxygen. First, mass loss assays were carried out at 100, 200, and 280 °C for 1000 h using pure Methyl Stearate (MS), 5% Methyl Oleate in Methyl Stearate (MS-5% MO), and 5% Methyl Linoleate in Methyl Stearate (MS-5% ML). Next, chemical changes in FAMEs were studied using FTIR, TGA, and GC/MS. SEM/EDS analysis allowed us to inspect the aluminum surfaces and their chemical characterization. We estimated higher corrosion rates for MS assays than those of unsaturated methyl ester mixtures. In a separate set of experiments, we used electrochemical techniques (potentiodynamic polarization, linear polarization resistance, and electrochemical impedance spectroscopy) to investigate aluminum corrosion induced by thermal-degraded products from FAMEs at 100, 200, and 280 °C for 300 h able to dissolve in aqueous extracts. These electrochemical experiments revealed that the products in the aqueous extracts from the unsaturated methyl ester mixture form a passive layer on the Al surface thicker than pure MS at the corresponding degradation temperatures.
PubMed: 38673181
DOI: 10.3390/ma17081821 -
PloS One 2024Irritable bowel syndrome (IBS) is one of the most common functional bowel disorders and dysmetabolism plays an important role in the pathogenesis of disease.... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Irritable bowel syndrome (IBS) is one of the most common functional bowel disorders and dysmetabolism plays an important role in the pathogenesis of disease. Nevertheless, there remains a lack of information regarding the causal relationship between circulating metabolites and IBS. A two-sample Mendelian randomization (MR) analysis was conducted in order to evaluate the causal relationship between genetically proxied 486 blood metabolites and IBS.
METHODS
A two-sample MR analysis was implemented to assess the causality of blood metabolites on IBS. The study utilized a genome-wide association study (GWAS) to examine 486 metabolites as the exposure variable while employing a GWAS study with 486,601 individuals of European descent as the outcome variable. The inverse-variance weighted (IVW) method was used to estimate the causal relationship of metabolites on IBS, while several methods were performed to eliminate the pleiotropy and heterogeneity. Another GWAS data was used for replication and meta-analysis. In addition, reverse MR and linkage disequilibrium score regression (LDSC) were employed for additional assessment. Multivariable MR analysis was conducted in order to evaluate the direct impact of metabolites on IBS.
RESULTS
Three known and two unknown metabolites were identified as being associated with the development of IBS. Higher levels of butyryl carnitine (OR(95%CI):1.10(1.02-1.18),p = 0.009) and tetradecanedioate (OR(95%CI):1.13(1.04-1.23),p = 0.003)increased susceptibility of IBS and higher levels of stearate(18:0)(OR(95%CI):0.72(0.58-0.89),p = 0.003) decreased susceptibility of IBS.
CONCLUSION
The metabolites implicated in the pathogenesis of IBS possess potential as biomarkers and hold promise for elucidating the underlying biological mechanisms of this condition.
Topics: Humans; Irritable Bowel Syndrome; Genome-Wide Association Study; Mendelian Randomization Analysis; Carnitine; Causality
PubMed: 38568932
DOI: 10.1371/journal.pone.0298963 -
Pharmaceutics Mar 2024The rice bran and rice bran wax of the KJ CMU107 rice strain were investigated as potential tablet lubricants in a directly compressed tablet formulation. Stabilized...
The rice bran and rice bran wax of the KJ CMU107 rice strain were investigated as potential tablet lubricants in a directly compressed tablet formulation. Stabilized full-fatted rice bran (sFFRB), stabilized defatted rice bran (sDFRB), and rice bran wax (RBW) extracted and purified from crude rice bran oil (cRBO) were tested. Two commercial lubricants, including magnesium stearate (MGS) and hydrogenated cottonseed oil (HVO), were employed as the standards in the formulated mixtures, which contained spray-dried rice starch (SDRS) as a diluent. The tableting was carried out for each formulation, and the obtained tablets were physically and mechanically evaluated. Among the parameters investigated were the general appearance, ejection force, weight variation, hardness, friability, and disintegration time. The powder flow was also determined for each formulation. The results showed that the tablet ejection forces for all the lubricated formulations (58-259 N) were significantly lower than that of the non-lubricated control formulation (349 N). The use of sFFRB as a lubricant at 0.5-2.0% / could lower the ejection force up to 78%, but the hardness reduced so drastically that the formulations failed the friability test due to the chipping of the tablets' edges. Moreover, sDFRB performed significantly better as the use at 0.5-1.0% / in the formulation helped to lower the ejection forces by up to 80% while maintaining the changes in the tablet hardness within 10%. RBW functioned effectively as a tablet lubricant at a concentration of 0.5% /, yielding tablets with good strength comparable to standard HVO lubricant while helping to reduce the ejection force by 82%. In formulations with good lubrication, i.e., friability < 1%, the powder flow was improved, and the tablet disintegration times were within the same range as the control and HVO formulations. In conclusion, sDFRB displayed a lubricant property at concentrations between 0.5 and 1.0% /, with slightly negative effects on the tablet hardness. RBW from KJ CMU107 rice was an effective tablet lubricant at 0.5% /, with no effect on tablet hardness. Both materials can be further developed for use as commercial lubricants in direct compression.
PubMed: 38543322
DOI: 10.3390/pharmaceutics16030428 -
Foods (Basel, Switzerland) Mar 2024Starch-lipid complexes were prepared from high amylose starch (HAS) with stearic acid (SA) or potassium stearate (PS) at different molar concentrations. The complexes...
Structural Features, Physicochemical Properties, and In Vitro Digestibility of the Starch-Lipid Complexes Formed between High Amylose Starch and Stearic Acid or Potassium Stearate.
Starch-lipid complexes were prepared from high amylose starch (HAS) with stearic acid (SA) or potassium stearate (PS) at different molar concentrations. The complexes (HAS-PS) formed between HAS and PS showed polyelectrolyte characteristics with ζ-potential ranging from -22.2 to -32.8 mV, and the electrostatic repulsion between anionic charges restricted the starch chain reassociation and facilitated the formation of V-type crystalline structures upon cooling. The hydrophobic effects enabled recrystallization of the SA, and the HAS-SA complexes exhibited weaker V-type crystalline structures than the HAS-PS complexes; both HAS-SA/PS complexes were of a similar "mass fractal" type, with a dimension varied from 2.15 to 2.96. The HAS-SA complexes had a considerable content of resistant starch (RS, 16.1~29.2%), whereas negligible RS was found in the HAS-PS complexes. The findings from the present study imply that the molecular order of starch chains and the macro-structures of starch particles are more important to regulate the digestibility of starch-lipid complexes than the crystalline structures.
PubMed: 38540849
DOI: 10.3390/foods13060859 -
Metabolites Mar 2024Consumption of high-fat diets (HFD) is associated with brain alterations, including changes in feeding behavior, cognitive decline, and dementia. Astrocytes play a role...
Consumption of high-fat diets (HFD) is associated with brain alterations, including changes in feeding behavior, cognitive decline, and dementia. Astrocytes play a role in HFD-induced neuroinflammation and brain dysfunction; however, this process is not entirely understood. We hypothesized that exposure to saturated fatty acids can compromise astrocyte viability and mitochondrial function. The C6 (astrocytes) cell line was treated with palmitate or stearate (200 µM and 400 µM) for 6 h. Cell viability, morphology, inflammatory markers, and oxidative stress were evaluated. To assess mitochondrial function, various parameters were measured (membrane potential, mass, respiration, and complex activities). We observed that 6 h of treatment with 400 µM palmitate decreased cell viability, and treatment with 200 µM palmitate changed the astrocyte morphology. Palmitate increased inflammatory markers (TNF-α and IL6) but did not induce oxidative stress. Palmitate significantly decreased the mitochondrial membrane potential and mitochondrial mass. Complex I activity also decreased in palmitate-treated cells; however, no changes were observed in mitochondrial respiration. In conclusion, palmitate, a saturated fatty acid, induces inflammation and impairs mitochondrial function, leading to reduced astrocytic cell viability and changes in cellular morphology. Our study provides valuable insights into the potential mechanisms underlying the relationship between saturated fatty acids, astrocytes, and mitochondrial function in obesity-related brain dysfunction.
PubMed: 38535321
DOI: 10.3390/metabo14030161