Search

Introduction: Bile acids are steroidal compounds, which contain 24 carbon atoms. They can be classified into two major groups: primary and secondary.The most abundant bile acids: The primary bile acids include cholic acid and chenodeoxycholic acid, while the major secondary bile acids are deoxycholic acid and litocholic acid. Bile acids are important physiological agents for intestinal absorption of nutrients and are used for biliary lipid secretion, toxic metabolites and xenobiotics. The aim of this paper is to analyze biosynthesis and biotransformation of bile acids, as preparation for practical usage in laboratory and clinical conditions. Topic: Biosynthesis and biotransformation of bile acids: The biosynthesis of bile acids is the dominant metabolic pathway for catabolism of cholesterol in humans. The classical route of biosynthesis of bile acids is embarking on the conversion of cholesterol into 7α−hydroxycholesterol using enzyme 7α−cholesterol hydroxylase (CYP7A1). This enzyme is one of the microsomal cytochrome P450 enzyme is localized exclusively in the liver. Classical road is the main road in the biosynthesis of bile acids, and its total contribution amounts to 90% for people, and 75% in mice. CYP 7A1 enzyme is considered to be sensitive to the inhibition of carbon monoxide, and the condition for the eff ect of NADPH, the oxygen, lecithin, and the NADPH-cytochrome P450 reductase. Bile acids are important signaling molecules and metabolic controls which activate the nuclear receptor and the G protein-coupled receptors (GPCR), a signaling lipid regulation of the liver, glucose and energy homeostasis. Also, bile acids maintain metabolic homeostasis. Biotransformation of bile acids: The conversion of cholesterol into bile acids just important for maintenance of cholesterol homeostasis, but also to prevent the accumulation of cholesterol, triglycerides and toxic metabolites as well as violations of the liver and other organs. Enterohepatic circulation of bile acids from the liver to the intestine and back to the liver occupies the most important role in the processes of absorption and distribution, as well as in metabolic regulation and homeostasis. Conclusions: This physiological process is complicated and regulates the membrane transport system in the liver and intestine by means of nuclear receptors. It is very dangerous fact that toxic bile acids may be causes of inflammation, apoptosis and cell death. On the other hand activated GPCR signaling and nuclear bile acid protects against inflammation of the liver, intestine and macrophages. Bile acid metabolism disorders cause cholestatic liver disease, dyslipidemia, fatty liver disease, cardiovascular disease and diabetes. [ABSTRACT FROM AUTHOR]

[Display omitted] Deoxycholic acid (DCA), lithocholic acid (LCA), and ursodeoxycholic acid (UDCA) are bile acids that may serve as permeation enhancers when incorporated within the nanogel matrix for drug delivery in the inner ear. In this study, thermoresponsive nanogels were formulated with DCA, LCA and UDCA and their rheological properties and biocompatibility were assessed. The impact of nanogel on cellular viability was evaluated via cell viability assay, the impact of nanogels on cellular bioenergetic parameters was estimated by Seahorse mito-stress test and glycolysis-stress test, while the presence of intracellular free radicals was assessed by reactive oxygen species assay. Nanogels showed a high level of biocompatibility after 24-hour exposure to auditory and macrophage cell lines, with minimal cytotoxicity compared to untreated control. Incubation with nanogels did not alter cellular respiration and glycolysis of the auditory cell line but showed possible mitochondrial dysfunction in macrophages, suggesting tissue-dependent effects of bile acids. Bile acid-nanogels had minimal impact on intracellular reactive oxygen species, with LCA demonstrating the most pro-oxidative behaviour. This study suggests that thermoresponsive nanogels with bile acid, particularly DCA and UDCA, may be promising candidates for inner ear drug delivery. [ABSTRACT FROM AUTHOR]

The biocompatibility and effects on cells' bioactivity of developed pharmaceuticals are crucial properties, required to permit their safe delivery. Nanogel matrices offer a promising role in emerging pharmaceutics; however, it is crucial that they and their excipients do not demonstrate detrimental effects on the cells to which they interact. This study investigated the use of Teflon and the secondary bile acid deoxycholic acid in the formation of novel nanogel matrices. Each has properties which may be of benefit for the nanogels created and their use in the pharmaceutical industry. Rheological parameters and scanning electron microscopy studies were conducted. In order to assess the developed nanogels' impacts on cellular bioactivity, studies using Seahorse assays were conducted on three cell types, hepatic, muscle and pancreatic beta cells. Results demonstrated the addition of Teflon did not alter the morphological characteristics of resulting nanogels or the metabolic profiles of the cell lines. Interestingly, pancreatic beta cells highlighted the potential of Teflon to exert a protective profile from mitochondrial damage. Overall, the developed nanogels showed potentially promising profiles in certain studies conducted which may lead to future research. [Display omitted] [ABSTRACT FROM AUTHOR]

Deoxycholic acid (DCA) is a bile acid capable of forming micelles and modifying the properties of hydrogels. We incorporated DCA in sodium alginate (SA) and poloxamer 407 matrices creating novel DCA-copolymer hydrogel for therapeutic delivery. Hydrogels were assessed for common rheological properties. Biocompatibility and biological effect were examined on various cell lines. Cell viability was determent in normal and various hypoxic conditions, and full mitochondrial bioenergetic parameters were assessed in cell lines in order to illustrate hydrogel effects on survival, and cell metabolic profile within the hydrogels. Obtained data suggest that a low dose of DCA in permeable, biocompatible hydrogels can be beneficial for cells to combat hypoxic conditions. [Display omitted] • Effects of hydrogels with deoxycholic acid were investigated on cells. • Hydrogels with bile acid may promote anaerobic metabolism in cells. • Hydrogels with bile acid may promote non-mitochondrial oxygen consumption in cells. • An increase in bile acid concentration leads to a decrease in beta cells' viability. [ABSTRACT FROM AUTHOR]

We have demonstrated a permeation-enhancing effect of deoxycholic acid (DCA), the bile acid, in diabetic rats. In this study, we designed DCA-based microcapsules for the oral delivery of the antilipidemic drug probucol (PB), which has potential antidiabetic effects. We aimed to further characterize these microcapsules and examine their pH-dependent release properties, as well as the effects of DCA on their stability and mechanical strength at various pH and temperature values. Using the polymer sodium alginate (SA), we prepared PB-SA (control) and PB-DCA-SA (test) microcapsules. The microcapsules were examined for drug content, size, surface composition, release, Micro-CT cross-sectional imaging, stability, Zeta potential, mechanical strength, and swelling characteristics at different pH and temperature values. The microencapsulation efficiency and production yield were also examined. The addition of DCA resulted in microcapsules with a greater density and with reduced swelling at a pH of 7.8 and at temperatures of 25°C and 37°C (p< 0.01). The size, surface composition, production yield, and microencapsulation efficiency of the microcapsules remained similar after DCA addition. PB-SA microcapsules produced multiphasic PB release, while PB-DCA-SA microcapsules produced monophasic PB release, suggesting more controlled PB release in the presence of DCA. The PB-DCA-SA microcapsules showed good stability and a pH-sensitive uniphasic release pattern, which may suggest potential applications in the oral delivery of PB in diabetes. [ABSTRACT FROM PUBLISHER]

Introduction: Bile acid-based drug encapsulation for oral delivery has been recently explored in our laboratory and has shown to be beneficial in terms of drug-targeted delivery and release profile, but stability at various temperatures has not previously been examined; hence, this is the aim of this study. Methods: Various types of bile acid-based microcapsules containing the drug metformin were produced and tested for accelerated temperature-controlled profiles, as well as morphology, elemental composition, drug content, resilience, floatability, wettability and release profiles at various pH values. Results: Accelerated temperature-controlled analysis showed negligible effects on morphology, size, or shape at very low temperatures (below 0 °C), while higher temperatures (above 25 °C) caused alterations. Drug contents, morphology and elemental composition remained similar, while wettability and the release profiles showed formulation-dependent effects. Discussion and Conclusion: Results suggest that bile acid-based microcapsules containing metformin are affected by temperature; hence, their shelf life is likely to be affected by storage temperature, all of which have a direct impact on drug release and stability profiles. [ABSTRACT FROM AUTHOR]

Major problem for diabetic patients represents damage of blood vessels and the oxidative stress of the brain cells due to increased concentration of free radicals and poor nutrition of brain cells. Gliclazide has antioxidative properties and poor blood brain barrier (BBB) penetration. Bile acids are known for their hypoglycemic effect and as promoters of drug penetration across biological membranes. Accordingly, the aim of this study is to investigate whether the bile acid (deoxycholic acid) can change the permeation of gliclazide, through the blood brain barrier of a ratmodel type-1 diabetes. Twenty-fourmale Wistar rats were randomly allocated to four groups, of which, two were given alloxan intraperitoneally (100mg/kg) to induce diabetes. One diabetic group and one healthy group were given a bolus gliclazide intra-arterially (20mg/kg), while the other two groups apart from gliclazide got deoxycholic acid (4mg/kg) subcutaneously. Blood samples were collected 30, 60, 150, and 240 seconds after dose, brain tissues were immediately excised and blood glucose and gliclazide concentrations were measured. Penetration of gliclazide in groups without deoxycholic acid pretreatment was increased in diabetic animals compared to healthy animals. Also in both, the healthy and diabetic animals, deoxycholic acid increased the permeation of gliclazide through that in BBB. [ABSTRACT FROM AUTHOR]

• The influence of intestinal microbiota and bile acids present in the intestinal content should be considered as variables influencing the bioavailability and patients response to gliclazide • Probiotic bacteria significantly increase the permeability of gliclazide across PAMPA membrane • Bile acids decreased the permeability of gliclazide across PAMPA membrane • Compared to cholic acid, deoxycholic acid exhibits more pronounced effect, by forming more stable complexes with gliclazide. forms more stable complexes with gliclazide, reducing the permeation of the drug Image, graphical abstract Gut microbiota and bile acids possess the ability to modify absorption and pharmacokinetic profile of numerous drugs. Since the variability of gliclazide response in patients cannot be explained only by genetic factors, the influence of gut microbiota and bile acids should be considered. The aim of this study was to determine the effects of probiotic bacteria and bile acids on the gliclazide permeability. The permeability of gliclazide with and without probiotic bacteria and bile acids (cholic acid, CA and deoxycholic acid, DCA) was tested using in vitro PAMPA model, at three different pH values (5.8, 6.5 and 7.4). Concentrations of gliclazide were determined by HPLC analysis. The interactions of gliclazide and bile acids were also investigated by molecular mechanics calculations (MM2). Probiotic bacteria significantly increased the permeability of gliclazide across the PAMPA membrane at all observed pH values while the total amount of gliclazide during incubation with bacteria was significantly reduced at pH 7.4, which could be a consequence of partial metabolism of the drug by enzymes of probiotic bacteria. Bile acids decreased the permeability of gliclazide through PAMPA membrane, with more pronounced effects of DCA, by forming more stable complexes with gliclazide. Given that probiotic bacteria and bile acids are naturally present in the gut and that each individual has a specific bacterial fingerprint, future research should extend the explanation of their effect on the gliclazide bioavailability and therapy individualization in in vivo conditions. [ABSTRACT FROM AUTHOR]