Glycation and drug binding by serum albumin.

Accumulation of glycation products in patients with hyperglycaemic conditions can lead to their reaction with the proteins in the human system such as serum albumin, haemoglobin, insulin, plasma lipoproteins, lens proteins and collagen among others which have important biological functions. Therefore, it is important to understand if glycation of these proteins affects their normal action not only qualitatively, but also importantly quantitatively. Glycation of human serum albumin can easily be carried out over period of weeks and its drug transportability may be examined, in addition to characterisation of the amadori products. A combination of ultrasensitive isothermal titration calorimetry, differential scanning calorimetry, spectroscopy and chromatography provides structure-property-energetics correlations which are important to obtain mechanistic aspects of drug recognition, conformation of the protein, and role of amadori products under conditions of glycation. The role of advance glycation end products is important in recognition of antidiabetic drugs. Further, the extent of glycation of the protein and its implication on drug transportability investigated by direct calorimetric methods enables unravelling mechanistic insights into role of functionality on drug molecules in the binding process, and hinderance in the recognition process, if any, as a result of glycation. It is possible that the drug binding ability of the protein under glycation conditions may not be adversely affected, or may even lead to strengthened ability. Rigorous studies on such systems with diverse functionality on the drug molecules is required which is essential in deriving guidelines for improvements in the existing drugs or in the synthesis of new molecular entities directed towards addressing diabetic conditions.

Flaking of millets and its impact on bioactivity, pasting, digestibility, structural and thermal properties.

Five different millets (foxtail, little, barnyard, kodo and browntop) with and without sprouting were subjected to flaking. Phytic acid and phenolic content tends to decrease significantly, whereas antioxidant activity increased up to 77.32% on flaking of millets. A significant decrease in peak and final viscosity was observed in millet flakes. A-type diffraction pattern was predominant for unsprouted millets whereas the flaked millets showed V-type crystallinity. The protein digestibility significantly increased up to 37.77% in flakes made from sprouted millets. The mineral bioavailability upon flaking of millets increased, especially Ca (88.22% for little), Fe (43.04% for barnyard) and Zn (61.77% for kodo), which is attributed to the reduction in phytic acid. Flaking, however, led to an increase in rapidly and slowly digestible starch with a corresponding decrease in resistant starch. Among the unsprouted and sprouted millet flakes, foxtail received the highest sensory scores for overall acceptability.

Predictive model for the surface melting and puffing of freeze-dried amorphous materials.

It is thought that surface melting and puffing of freeze-dried amorphous materials are related to the difference between the surface temperature (Tsur) and freeze-concentrated glass transition temperature (Tg') of the materials. Although Tg' is a material-specific parameter, Tsur is affected by the type and amount of solute and freeze-drying conditions. Therefore, it will be practically useful for preventing surface melting and puffing if Tsur can be calculated using only the minimum necessary parameters. This study aimed to establish a predictive model for the surface melting and puffing of freeze-dried amorphous materials according to the calculated Tsur. First, a Tsur-predictive model was proposed under the thermodynamic equilibrium assumptions. Second, solutions with various solute mass fractions of sucrose, maltodextrin, and sucrose-maltodextrin mixture were prepared, and three material-specific parameters (Tg', unfrozen water content, and true density) were experimentally determined. According to the proposed model with the parameters, the Tsur of the samples was calculated at chamber pressures of 13, 38, and 103 Pa. The samples were freeze-dried at the chamber pressures, and their appearance was observed. As expected, surface melting and puffing occurred at calculated Tsur > Tg' with some exceptions. The water activity (aw) of the freeze-dried samples increased as the Tsur - Tg' increased. This will have resulted from surface melting and puffing, which created a covering film, thereby preventing subsequent dehydration. The observations suggest that the proposed model is also useful for predetermining the drying efficiency and storage stability of freeze-dried amorphous materials.

Functional and Structural Properties of Cytoplasmic Tropomyosin Isoforms Tpm1.8 and Tpm1.9.

The actin cytoskeleton is one of the most important players in cell motility, adhesion, division, and functioning. The regulation of specific microfilament formation largely determines cellular functions. The main actin-binding protein in animal cells is tropomyosin (Tpm). The unique structural and functional diversity of microfilaments is achieved through the diversity of Tpm isoforms. In our work, we studied the properties of the cytoplasmic isoforms Tpm1.8 and Tpm1.9. The results showed that these isoforms are highly thermostable and differ in the stability of their central and C-terminal fragments. The properties of these isoforms were largely determined by the 6th exons. Thus, the strength of the end-to-end interactions, as well as the affinity of the Tpm molecule for F-actin, differed between the Tpm1.8 and Tpm1.9 isoforms. They were determined by whether an alternative internal exon, 6a or 6b, was included in the Tpm isoform structure. The strong interactions of the Tpm1.8 and Tpm1.9 isoforms with F-actin led to the formation of rigid actin filaments, the stiffness of which was measured using an optical trap. It is quite possible that the structural and functional features of the Tpm isoforms largely determine the appearance of these isoforms in the rigid actin structures of the cell cortex.

How Depolymerization-Based Plasticization Affects the Process of Cold Crystallization in Poly(P-Dioxanone).

The self-plasticization, i.e., the increase in the polymer chains' mobility by including its monomer, has a major impact on a polymer's structural, thermal, and mechanical properties. In this study, differential scanning calorimetry (DSC), optical and Raman microscopies, thermo-mechanical analysis (TMA), size exclusion chromatography equipped with a multi-angle light scattering detector (SEC-MALS), and X-ray diffraction analysis (XRD) are used to investigate the effect of thermally induced self-plasticization of poly-(p-dioxanone), PDX, on the crystal growths from the amorphous and molten states. Significant changes in the crystallization behavior and mechanical properties of PDX are found only for samples self-plasticized at the depolymerization temperature (Td) above 150 °C. The intense self-plasticization leads to the decrease of the crystallization temperature, increase of the crystal growth rapidity, disappearance of the distinct α→α' polymorphic transition, reduction of the overall melting temperature, and segregation of the redundant monomer. Although the morphology of the crystalline phase has a major impact on the mechanical properties of PDX, the self-plasticization itself does not seem to result in any major changes in the magnitude, localization, or morphology of formed crystallites (these are primarily driven by the temperature of crystal growth). The manifestation of the variable activation energy concept is discussed for the present crystallization data.

Characterization of structure of peptidyl-tRNA hydrolase from Enterococcus faecium and its inhibition by a pyrrolinone compound.

In bacteria, peptidyl-tRNA hydrolase (Pth, E.C. 3.1.1.29) is a ubiquitous and essential enzyme for preventing the accumulation of peptidyl-tRNA and sequestration of tRNA. Pth is an esterase that cleaves the ester bond between peptide and tRNA. Here, we present the crystal structure of Pth from Enterococcus faecium (EfPth) at a resolution of 1.92 Å. The two molecules in the asymmetric unit differ in the orientation of sidechain of N66, a conserved residue of the catalytic site. Enzymatic hydrolysis of substrate α-N-BODIPY-lysyl-tRNALys (BLT) by EfPth was characterized by Michaelis-Menten parameters KM 163.5 nM and Vmax 1.9 nM/s. Compounds having pyrrolinone scaffold were tested for inhibition of Pth and one compound, 1040-C, was found to have IC50 of 180 nM. Antimicrobial activity profiling was done for 1040-C. It exhibited equipotent activity against drug-susceptible and resistant S. aureus (MRSA and VRSA) and Enterococcus (VSE and VRE) with MICs 2-8 µg/mL. 1040-C synergized with gentamicin and the combination was effective against the gentamicin resistant S. aureus strain NRS-119. 1040-C was found to reduce biofilm mass of S. aureus to an extent similar to Vancomycin. In a murine model of infection, 1040-C was able to reduce bacterial load to an extent comparable to Vancomycin.

Solid-state reaction of alkylamines with CO2 in ambient air.

This paper explores possible procedures to accelerate CO2 capture from ambient air by a crystalline alkylamine surfactant (octadecylamine), leading to the corresponding crystalline ammonium-carbamate. Conversion of the amine to the carbamate, in different conditions, is studied by four different techniques: WAXD, FTIR, TGA, and DSC. The WAXD study also gives relevant information on the crystal structures of both amine and derived carbamate. Kinetics of reactions of the crystalline amine are mainly studied by DSC scans, by evaluating melting enthalpies of residual amine. The kinetics of conversion of the amine in ambient CO2 is strongly accelerated by ball milling with full conversion achieved after only 4h, while the reaction kinetics of amine powder simply exposed to ambient CO2 is complete only after nearly 103 h. A substantial increase in kinetics of the solid-state amine reaction with ambient CO2 can be also achieved by increasing the temperature up to 50°C, i.e. at a temperature slightly lower than amine melting. However, the time for full conversion remains much higher than for room-temperature ball-milled amine (roughly 102h vs 4h). Hence, suitable ball-milling procedures can lead to complete and relatively fast conversion of the crystalline amine to the crystalline ammonium-carbamate, even with ambient CO2.

Printability and Thermophysical Properties of Three-Dimensional-Printed Food Based on "Cochayuyo" Durvillaea antarctica Seaweed Flour.

This research assessed the feasibility of adding Cochayuyo seaweed flour (at 30, 50, and 70% levels) to rice flour-based paste to improve its 3D printing quality. The paste's rheological properties, printing quality, texture profile, thermal properties, and color of 3D-printed foods were explored. Results showed that pastes with Cochayuyo addition exhibited shear-thinning behavior, and viscosity increased with increased Cochayuyo concentration. Viscoelastic properties and a Texture Profile Analysis (TPA) revealed that Cochayuyo improved mechanical strength and made the paste easier to flow, improving printed food's extrudability, fidelity, and shape retention, which was better observed in RC50 and RC70 printed at 15 mm s-1. A differential scanning calorimetry (DSC) analysis showed a partial substitution of rice flour for Cochayuyo flour in the formulation. This increased the onset and melting peak temperatures and reduced the enthalpy of fusion. CIE color parameters a*, b*, and L* showed that Cochayuyo addition increased the color to yellow and red; however, lightness was considerably reduced. Therefore, Cochayuyo flour could have the potential to be used for the manufacture improvement of 3D-printed food with better rheological, mechanical, thermal, printing quality, and nutritional properties, making possible the exploitation of the native Cochayuyo seaweed, which is highly available in Chile.

Investigation of miltefosine-model membranes interactions at the molecular level for two different PS levels modeling cancer cells.

Miltefosine (MLT) is a broad-spectrum drug included in the alkylphospholipids (APL) used against leishmania and various types of cancer. The most crucial feature of APLs is that they are thought to only kill cancerous cells without harming normal cells. However, the molecular mechanism of action of APLs is not completely understood. The increase in the phosphatidylserine (PS) ratio is a marker showing the stage of cancer and even metastasis. The goal of this research was to investigate the molecular effects of miltefosine at the molecular level in different PS ratios. The effects of MLT on membrane phase transition, membrane orders, and dynamics were studied using DPPC/DPPS (3:1) and DPPC/DPPS (1:1) multilayer (MLV) vesicles mimicking DPPS ratio variation, Differential Scanning Calorimetry (DSC), and Fourier Transform Infrared spectroscopy (FTIR). Our findings indicate that miltefosine is evidence at the molecular level that it is directed towards the tumor cell and that the drug's effect increases with the increase of anionic lipids in the membrane depending on the stage of cancer.

An improved linear systems model of hydrothermal isometric tension testing to aid in assessing bone collagen quality: Effects of ribation and type-2 diabetes.

This study sought to further develop and validate a previously proposed physics-based model that maps denaturation kinetics from differential scanning calorimetry (DSC) to the isometric tension generated during hydrothermal isometric tension (HIT) testing of collagenous tissues. The primary objectives of this study were to verify and validate two physics-based model parameters: α, which indicates the amount of instantaneous isometric tension developed per unit of collagen denaturation, and ß, which captures the proportionality between temperature and the generated isometric tension post denaturation initiation. These parameters were used as measures of bone collagen quality, employing data from HIT and DSC testing of human bone collagen from two previous studies. Additionally, given the physical basis of the model, the study aimed to further validate Max.Slope, the rate of change in isometric tensile stress with change in temperature, as an independent measure of collagen network connectivity. Max.Slope has previously been positively correlated with measures of cortical bone fracture resistance. Towards this verification and validation, the hypotheses were a) that α would correlate strongly with HIT denaturation temperature, Td, and the enthalpy of melting (ΔH) from DSC, and b) that ß would correlate positively and strongly with Max.Slope. The model was employed in the analysis of HIT-DSC data from the testing of demineralized bone collagen isolated from cadaveric human femurs in two prior studies. In one study, data were collected from HIT-DSC testing of cortical bone collagen from 74 donors. Among them, 38 had a history of type 2 diabetes +/- chronic kidney disease, while the remaining 36 had no history of T2D again with or without CKD. Cortical bone specimens were extracted from the lateral mid-shaft. The second study involved 15 donor femora, with four cortical bone specimens extracted from each. Of these four, two specimens underwent a 4-week incubation in 0.1 M ribose at 37 °C to induce non-enzymatic ribation and advanced glycation endproducts, while the other two served as non-ribated controls. The examination involved investigating correlations between the model parameters α and ß and various measures, such as Max.Slope, Td, ΔH, age, and duration of type 2 diabetes. The results revealed positive correlations between the model parameter ß and Max.Slope (r = 0.55-0.58). The parameter α was found to be associated with Td, but also sensitive to the shape of the HIT curve around Td resulting in difficulties with variability and interpretation. As a result, while both hypotheses are confirmed, Max.Slope and ß are better indicators of bone collagen quality because they are measures of the connectivity or, more generally, the integrity of the bone collagen network.

Phase Transition Thermodynamics of 1,3,5-Tris-(α-naphthyl)benzene: Theory and Experiment.

1,3,5-Tris-(α-naphthyl)benzene is an organic non-electrolyte with notable stability of an amorphous phase. Its glassy and supercooled liquid states were previously studied by spectroscopic and calorimetric methods. Despite the continuing interest in its amorphous state and, particularly, vapor-deposited glasses, the thermodynamic parameters of the vaporization of 1,3,5-tris-(α-naphthyl)benzene have not been obtained yet. Likewise, the reliable evaluation of the thermodynamic parameters of fusion below the melting point, required to establish the thermodynamic state of its glass, is still an unsolved problem. In this work, the heat capacities of crystalline and liquid phases, the temperature dependence of the saturated vapor pressures, fusion and vaporization enthalpies were determined using differential and fast scanning calorimetry and were verified using the estimates based on solution calorimetry. The structural features of 1,3,5-tris-(α-naphthyl)benzene are discussed based on the computations performed and the data on the molecular refractivity. The consistency between the values obtained by independent techniques was demonstrated.

Exogenous polyserine fibrils change membrane properties of phosphatidylcholine-liposome and red blood cells.

The causative genes for neurodegenerative polyglutamine (polyQ) diseases produce homopolymeric polyglutamine (polyQ), polyserine (polyS), polyalanine (polyA), polycysteine (polyC), and polyleucine (polyL) sequences by repeat-associated non-AUG (RAN) translation. The cytotoxicity of the intracellular polyQ and RAN products has been extensively investigated. However, little is known about the toxicity of the extracellular polyQ and RAN products on the membranes of viable cells. Because polyQ aggregates induce a deflated morphology of a model membrane, we hypothesized that extracellular polyQ and RAN products might affect the membrane properties of viable cells. In this study, we demonstrated that exogenous polyS fibrils but not polyS or polyQ non-fibril aggregates altered the thermal phase transition behavior of a model membrane composed of a phosphatidylcholine bilayer using differential scanning calorimetry. PolyS fibrils induced morphological changes in viable red blood cells (RBCs). However, both polyS and polyQ non-fibril aggregates had no effects on RBCs. These results highlight the possibility that extracellular fibrils generated from RAN products may alter the properties of neuronal cell membranes, which may contribute to changes in the brain pathology.

Enzymatic degradation of pea fibers changes pea protein concentrate functionality.

Pea proteins are gaining increased interest from both the food industry as well as from consumers. Pea protein isolates (PPI) excel at forming meat-like textures upon heating while pea protein concentrates (PPC) are more challenging to transform into highly sought-after foods. PPCs are richer in dietary fibers (DF) and are more sustainable to produce than PPI. In this work, degradative enzymes were used to modify the functionality of PPC-water blends with a focus on texturization upon heating. Three enzyme solutions containing ß-glucanases, hemicellulases, pectinases, xylanase, and cellulases were added to 65 wt% PPC blends. The effect of these enzymatic pretreatments was measured by monitoring the torque in a mixing reactor during blending, differential scanning calorimetry (DSC), high-pressure shear rheology (HPSR), and DF content and size analysis. Four endothermic peaks were detected in the DSC thermograms of PPC, namely at 63 °C, 77 °C, 105 °C and 123 °C. The first three peaks were attributed to phase transition and gelation temperatures of the starches and proteins constituting PPC. No endothermic peaks were measured for PPI blends. Enzyme solutions containing ß-glucanases, hemicellulases, pectinases, and xylanases increased the endothermic energy of all peaks, hinting at an effect on the gelation properties of PPC. The same enzymes decreased the resistance to flow of PPC blends and induced a shift of the weight average molecular weight (Mw) distribution of soluble dietary fibers (SDF) towards smaller values while increasing the fraction of SDF by decreasing the insoluble dietary fiber (IDF) content. The solution containing cellulases did not change the DSC results or the viscosity of the PPC mixture, nor did it affect the IDF and SDF contents. On the other hand HPSR measurements of heated PPC samples up to 125 °C showed that all tested enzyme solutions decreased the complex viscosity of PPC-water blends to values similar to PPI-water blends. We demonstrated that degradative enzymes can enhance the functionality of less refined protein-rich ingredients based on pea and other vegetal sources. Using optimized enzyme blends for targeted applications can prove to be a key changer in the development and improvement of sustainable protein-rich foods.

An Eutectic Mixture in the Tetrabutylammonium Bromide-Octanol System: Macroscopic and Microscopic Points of View.

An eutectic mixture of tetrabutylammonium bromide and octanol in the molar ratio 1-10 exhibited a melting point of -17 °C. This system was investigated by means of infrared spectroscopy, in the liquid and in the solid state. Classical molecular dynamics was performed to study the fine details of the hydrogen bond interactions established in the mixture. Both octanol and the mixtures displayed an almost featureless far-infrared spectrum in the liquid state but it becomes highly structured in the solid phase. DFT calculations suggest that new vibrational modes appearing in the mixture at low temperatures may be related to the population of the higher energy conformers of the alcohol. Mid-infrared spectroscopy measurements evidenced no shift of the CH stretching bands in the mixture compared to the starting materials, while the OH stretching are blue shifted by a few cm-1. Consistently, molecular dynamics provides a picture of the mixture in which part of the hydrogen bonds (HB) of pure octanol is replaced by weaker HB formed with the Br anion. Due to these interactions the ionic couple becomes more separated. In agreement with this model, the lengths of all HB are much larger than those observed in mixtures containing acids reported in previous studies.

Comprehensive Assessment of Cyclic Fatigue Strength in Five Multiple-File Nickel-Titanium Endodontic Systems.

The resistance of nickel-titanium endodontic instruments against cyclic fatigue failure remains a significant concern in clinical settings. This study aimed to assess the cyclic fatigue strength of five nickel-titanium rotary systems, while correlating the results with the instruments' geometric and metallurgical characteristics. A total of 250 new instruments (sizes S1/A1, S2/A2, F1/B1, F2/B2, F3/B3) from ProTaper Gold, ProTaper Universal, Premium Taper Gold, Go-Taper Flex, and U-Files systems underwent mechanical testing. Prior to experimental procedures, all instruments were meticulously inspected to identify irregularities that could affect the investigation. Using a stereomicroscope, design characteristics such as the number of spirals, length, spirals per millimeter, and average helical angle of the active blade were determined. The surface finishing characteristics of the instruments were examined using a scanning electron microscope. Differential scanning calorimetry was employed to establish the instruments' phase transformation temperatures, while energy-dispersive X-ray spectroscopy was utilized to analyze the elemental composition of the alloy. The instruments were subjected to cyclic fatigue testing within a stainless steel non-tapered artificial canal featuring a 6 mm radius and 86 degrees of curvature. Appropriate statistical tests were applied to compare groups, considering a significance level of 0.05. The assessed design characteristics varied depending on the instrument type. The least irregular surface finishing was observed in U-Files and Premium Taper Gold files, while the most irregular surface was noted in Go-Taper Flex. All instruments exhibited near-equiatomic proportions of nickel and titanium elements, whereas ProTaper Universal and U-Files instruments demonstrated lower phase transformation temperatures compared to their counterparts. Larger-sized instruments, as well as ProTaper Universal and U-Files, tended to display lower cyclic fatigue strength results. Overall, the design, metallurgical, and cyclic fatigue outcomes varied among instruments and systems. Understanding these outcomes may assist clinicians in making more informed decisions regarding instrument selection.

Biopolymer-Based Hydrogel Incorporated with Naproxen Sodium and Lidocaine Hydrochloride for Controlled Drug Delivery.

Sodium hyaluronate (HA) is a natural polysaccharide. This biopolymer occurs in many tissues of living organisms. The regenerating, nourishing, and moisturizing properties as well as the rheological properties of HA enable its application in the pharmaceutical industry as a carrier of medicinal substances. The aim of this work was to assess the release of naproxen sodium (Nap) in the presence of lidocaine hydrochloride (Lid) from the biopolymer-based hydrogels and to determine the respective kinetic parameters of this process. The possible interaction between the HA polysaccharide carrier and the selected drugs was also investigated. Three hydrogels containing Nap and Lid with different concentrations of the biopolymer were prepared. The release of Nap was studied by employing USP apparatus 5. The infrared study and differential scanning calorimetry analysis of physical mixtures and dried formulations were performed. The highest amount of Nap was released from the formulation with the lowest concentration of the biopolymer. The most representative kinetic model that described the dissolution of Nap was obtained through the Korsmeyer-Peppas equation. The release rate constants were in the range of 1.0 ± 0.1 × 10-2 min-n-1.7 ± 0.1 × 10-2 min-n. Lid did not influence the dissolution of Nap from the formulations tested; however, in the desiccated samples of assessed formulations, the interaction between the polysaccharide and both drugs was observed.

Understanding the stability of a plastic-degrading Rieske iron oxidoreductase system.

Rieske oxygenases (ROs) are a diverse metalloenzyme class with growing potential in bioconversion and synthetic applications. We postulated that ROs are nonetheless underutilized because they are unstable. Terephthalate dioxygenase (TPADO PDB ID 7Q05) is a structurally characterized heterohexameric α3ß3 RO that, with its cognate reductase (TPARED), catalyzes the first intracellular step of bacterial polyethylene terephthalate plastic bioconversion. Here, we showed that the heterologously expressed TPADO/TPARED system exhibits only ~300 total turnovers at its optimal pH and temperature. We investigated the thermal stability of the system and the unfolding pathway of TPADO through a combination of biochemical and biophysical approaches. The system's activity is thermally limited by a melting temperature (Tm) of 39.9°C for the monomeric TPARED, while the independent Tm of TPADO is 50.8°C. Differential scanning calorimetry revealed a two-step thermal decomposition pathway for TPADO with Tm values of 47.6 and 58.0°C (ΔH = 210 and 509 kcal mol-1, respectively) for each step. Temperature-dependent small-angle x-ray scattering and dynamic light scattering both detected heat-induced dissociation of TPADO subunits at 53.8°C, followed by higher-temperature loss of tertiary structure that coincided with protein aggregation. The computed enthalpies of dissociation for the monomer interfaces were most congruent with a decomposition pathway initiated by ß-ß interface dissociation, a pattern predicted to be widespread in ROs. As a strategy for enhancing TPADO stability, we propose prioritizing the re-engineering of the ß subunit interfaces, with subsequent targeted improvements of the subunits.

Higher Order Structure Characterization of Two Interdomain Disulfide Bond Variants of a Bispecific Monoclonal Antibody.

Characterization and understanding of protein higher order structure (HOS) is essential at all stages of biologics development. Here, two folding variants of a bispecific monoclonal antibody, the correctly folded form and an alternative configuration with reduced potency, were characterized by several HOS characterization techniques. Specifically, differential scanning calorimetry (DSC), circular dichroism (CD), Fourier-transform infrared spectroscopy (FTIR), Raman and Raman optical activity (ROA) spectroscopy were used together to elucidate the impacts of disulfide bond scrambling in the fused scFv domains on the structure and thermal stability of the antibody. This study illustrates the importance of selecting appropriate biophysical characterization techniques based on the nature and magnitude of the HOS change.

Solvent stabilizing effects on the order-disorder transition of schizophyllan in aqueous mixtures of carboxylic acids.

Schizophyllan is a triple helical ß-1,3-D-glucan, and shows the cooperative order-disorder transition in the aqueous solution at the triple helix state. In this paper, the solvent stabilizing effects of two carboxylic acids, acetic acid and citric acid, on the cooperative order-disorder transition of aqueous schizophyllan solution were investigated from DSC and SEC-MALS measurements. The transition temperature (Tr) was shifted to higher temperature with increasing the molar fraction of carboxylic acid in the mixture (x). The transition enthalpy (ΔHr) was increased with increasing x. These solvent stabilizing effects indicate that these carboxylic acid molecules were selectively associated with the branched side chains of schizophyllan to stabilize the ordered state. The composition dependencies of Tr and ΔHr were analyzed by the linear cooperative transition theory to estimate the association parameters between the side chains and carboxylic acid. The theoretical parameters obtained were compared with those for the other active substances for the transition to discuss the molecular interactions between the triple helix and carboxylic acid.

Formulation development, characterization, and evaluation of bedaquiline fumarate - Soluplus® - solid dispersion.

Bedaquiline fumarate (BQF) is classified as a BCS class II drug and has poor water solubility and dissolution rate, which ultimately compromises bioavailability. The objective of this study is to improve the biopharmaceutical properties of BQF through a solid dispersion system by using Soluplus®. Two solid dispersion systems were prepared i.e. binary solid dispersion (BSD) and ternary solid dispersion (TSD) where 14.31-fold and 20.43-fold increase in solubility of BQF was observed with BSD and TSD in comparison to BQF. In our previous research work, we explored the BSD and TSD of BQF with a crystalline polymer, poloxamer 188, which showed an increment in the solubility of BQF. In the current research, amorphous Soluplus® polymer was selected to formulate BSD and TSD with BQF and showed higher solubility than poloxamer 188. The various solid and liquid state characterization results confirmed the presence of an amorphous form of BQF inside solid dispersion. The Fourier transform infrared spectroscopy showed no chemical interactions between BQF and polymer. The cellular uptake results demonstrated higher uptake in Caco-2 cell lines. Pharmacokinetic studies showed enhanced solubility and bioavailability of TSDs. Hence, the present research shows a promising formulation strategy for enhancing the biopharmaceutical performance of BQF by increasing its solubility.