Differential scanning calorimetry in drug-membrane interactions.

Differential Scanning Calorimetry (DSC) is a central technique in investigating drug - membrane interactions, a critical component of pharmaceutical research. DSC measures the heat difference between a sample of interest and a reference as a function of temperature or time, contributing essential knowledge on the thermally induced phase changes in lipid membranes and how these changes are affected by incorporating pharmacological substances. The manuscript discusses the use of phospholipid bilayers, which can form structures like unilamellar and multilamellar vesicles, providing a simplified yet representative membrane model to investigate the complex dynamics of how drugs interact with and penetrate cellular barriers. The manuscript consolidates data from various studies, providing a comprehensive understanding of the mechanisms underlying drug - membrane interactions, the determinants that influence these interactions, and the crucial role of DSC in elucidating these components. It further explores the interactions of specific classes of drugs with phospholipid membranes, including non-steroidal anti-inflammatory drugs, anticancer agents, natural products with antioxidant properties, and Alzheimer's disease therapeutics. The manuscript underscores the critical importance of DSC in this field and the need for continued research to improve our understanding of these interactions, acting as a valuable resource for researchers.

How Does the Powder Mixture of Ibuprofen and Caffeine Attenuate the Solubility of Ibuprofen? Comparative Study for the Xanthine Derivatives to Recognize Their Intermolecular Interactions Using Fourier-Transform Infrared (FTIR) Spectra, Differential Scanning Calorimetry (DSC), and X-ray Powder Diffractometry (XRPD).

Molecular interactions between active pharmaceutical ingredients (APIs) and xanthine (XAT) derivatives were analyzed using singular value decomposition (SVD). XAT derivatives were mixed with equimolar amounts of ibuprofen (IBP) and diclofenac (DCF), and their dissolution behaviors were measured using high-performance liquid chromatography. The solubility of IBP decreased in mixtures with caffeine (CFN) and theophylline (TPH), whereas that of DCF increased in mixtures with CFN and TPH. No significant differences were observed between the mixtures of theobromine (TBR) or XAT with IBP and DCF. Mixtures with various molar ratios were analyzed using differential scanning calorimetry, X-ray powder diffraction, and Fourier-transform infrared spectroscopy to further explore these interactions. The results were subjected to SVD. This analysis provides valuable insights into the differences in interaction strength and predicted interaction sites between XAT derivatives and APIs based on the combinations that form mixtures. The results also showed the impact of the XAT derivatives on the dissolution behavior of IBP and DCF. Although IBP and DCF were found to form intermolecular interactions with CFN and TPH, these effects resulted in a reduction of the solubility of IBP and an increase in the solubility of DCF. The current approach has the potential to predict various interactions that may occur in different combinations, thereby contributing to a better understanding of the impact of health supplements on pharmaceuticals.

Influence of Oxygen Uptake on Pitch Carbon Fiber.

Carbon fiber precursor materials, such as polyacrylonitrile, pitch, and cellulose/rayon, require thermal stabilization to maintain structural integrity during conversion into carbon fiber. Thermal stabilization mitigates undesirable decomposition and liquification of the fibers during the carbonization process. Generally, the thermal stabilization of mesophase pitch consists of the attachment of oxygen-containing functional groups onto the polymeric structure. In this study, the oxidation of mesophase pitch precursor fibers at various weight percentage increases (1, 3.5, 5, 7.5 wt%) and temperatures (260, 280, 290 °C) using in situ differential scanning calorimetry and thermogravimetric analysis is investigated. The results are analyzed to determine the effect of temperature and weight percentage increase on the stabilization process of the fibers, and the fibers are subsequently carbonized and tested for tensile mechanical performance. The findings provide insight into the relationship between stabilization conditions, fiber microstructure, and mechanical properties of the resulting carbon fibers.

Enabling Efficient Design of Biological Formulations Through Advanced Characterization.

The present review summarizes the use of differential scanning calorimetry (DSC) and scattering techniques in the context of protein formulation design and characterization. The scattering techniques include wide angle X-ray diffractometry (XRD), small-angle neutron scattering (SANS) and small-angle X-ray scattering (SAXS). While DSC is valuable for understanding thermal behavior of the excipients, XRD provides critical information about physical state of solutes during freezing, annealing and in the final lyophile. However, as these techniques lack the sensitivity to detect biomolecule-related transitions, complementary characterization techniques such as small-angle scattering can provide valuable insights.

pH-Dependent Changes in Structural Stabilities of Bt Cry1Ac Toxin and Contrasting Model Proteins following Adsorption on Montmorillonite.

The environmental fate of insecticidal Cry proteins, including time-dependent conservation of biological properties, results from their structural stability in soils. The complex cascade of reactions involved in biological action requires Cry proteins to be in solution. However, the pH-dependent changes in conformational stability and the adsorption-desorption mechanisms of Cry protein on soil minerals remain unclear. We used Derjaguin-Landau-Verwey-Overbeek (DLVO) calculation and differential scanning calorimetry to interpret the driving forces and structural stabilities of Cry1Ac and two contrasting model proteins adsorbed by montmorillonite. The structural stability of Cry1Ac is closer to that of the "hard" protein, α-chymotrypsin, than that of the "soft" bovine serum albumin (BSA). The pH-dependent adsorption of Cry1Ac and α-chymotrypsin could be explained by DLVO theory, whereas the BSA adsorption deviated from it. Patch-controlled electrostatic attraction, hydrophobic effects, and entropy changes following protein unfolding on a mineral surface could contribute to Cry1Ac adsorption. Cry1Ac, like chymotrypsin, was partly denatured on montmorillonite, and its structural stability decreased with an increase in pH. Moreover, small changes in the conformational heterogeneity of both Cry1Ac and chymotrypsin were observed following adsorption. Conversely, adsorbed BSA was completely denatured regardless of the solution pH. The moderate conformational rearrangement of adsorbed Cry1Ac may partially explain why the insecticidal activity of Bt toxin appears to be conserved in soils, albeit for a relatively short time period.

Protein-liposome interactions: the impact of surface charge and fluidisation effect on protein binding.

At the dawn of a new nanotechnological era in the pharmaceutical field, it is very important to examine and understand all the aspects that influence in vivo behaviour of nanoparticles. In this point of view, the interactions between serum proteins and liposomes with incorporated anionic, cationic, and/or PEGylated lipids were investigated to elucidate the role of surface charge and bilayer fluidity in protein corona's formation. 1,2-dipalmitoyl-sn-glycero-3- phosphocholine (DPPC), hydrogenated soybean phosphatidylcholine (HSPC), and 1,2-dioctadecanoyl-sn-glycero-3-phosphocholine (DSPC) liposomes with the presence or absence of 1,2-dipalmitoyl-sn-glycero-3-phospho-(1'-rac-glycerol) (sodium salt) (DPPG), 1,2-di-(9Z-octadecenoyl)-3-trimethylammonium-propane (chloride salt) (DOTAP), and/or 1,2-dipalmitoylsn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-5000] (DPPE-PEG 5000) lipids were prepared by the thin-film hydration method. The evaluation of their biophysical characteristics was enabled by differential scanning calorimetry and dynamic and electrophoretic light scattering. The physicochemical characteristics of mixed liposomes were compared before and after exposure to foetal bovine serum (FBS) and were correlated to calorimetric data. Our results indicate protein binding to all liposomal formulations. However, it is highlighted the importance of surface charge and fluidisation effect to the extent of protein adsorption. Additionally, considering the extensive use of cationic lipids for innovative delivery platforms, we deem PEGylation a key parameter, because even in a small proportion can reduce protein binding, and thus fast clearance and extreme toxicity without affecting positive charge. This study is a continuation of our previous work about protein-liposome interactions and fraction of stealthiness (Fs) parameter, and hopefully a design road map for drug and gene delivery.

DMSO-Induced Unfolding of the Antifungal Disulfide Protein PAF and Its Inactive Variant: A Combined NMR and DSC Study.

PAF and related antifungal proteins are promising antimicrobial agents. They have highly stable folds around room temperature due to the presence of 3-4 disulfide bonds. However, unfolded states persist and contribute to the thermal equilibrium in aqueous solution, and low-populated states might influence their biological impact. To explore such equilibria during dimethyl sulfoxide (DMSO)-induced chemical unfolding, we studied PAF and its inactive variant PAFD19S using nuclear magnetic resonance (NMR) and differential scanning calorimetry (DSC). According to the NMR monitoring at 310 K, the folded structures disappear above 80 v/v% DMSO concentration, while the unfolding is completely reversible. Evaluation of a few resolved peaks from viscosity-compensated 15N-1H HSQC spectra of PAF yielded ∆G = 23 ± 7 kJ/M as the average value for NMR unfolding enthalpy. The NMR-based structures of PAF and the mutant in 50 v/v% DMSO/H2O mixtures were more similar in the mixed solvents then they were in water. The 15N NMR relaxation dynamics in the same mixtures verified the rigid backbones of the NMR-visible fractions of the proteins; still, enhanced dynamics around the termini and some loops were observed. DSC monitoring of the Tm melting point showed parabolic dependence on the DMSO molar fraction and suggested that PAF is more stable than the inactive PAFD19S. The DSC experiments were irreversible due to the applied broad temperature range, but still suggestive of the endothermic unfolding of PAF.

Triacylglycerol Composition and Chemical-Physical Properties of Cocoa Butter and Its Derivatives: NMR, DSC, X-ray, Rheological Investigation.

In recent years, the food industry has become increasingly involved in researching vegetable fats and oils with appropriate mechanical properties (ease of transport, processing, and storage) and a specific lipidic composition to ensure healthy products for consumers. The chemical-physical behavior of these matrices depends on their composition in terms of single fatty acids (FA). However, as we demonstrate in this work, these properties, as well as the absorption, digestion and uptake in humans of specific FAs, are also largely determined by their regiosomerism within the TriAcylGlycerols (TAG) moieties (sn-1,2,3 positions). The goal of this work is to study for the first time vegetable fats obtained directly from a sample of natural cocoa butter (CB) through a process that manipulates the distribution of FAs but not their nature. Even if the initial percentage of each FA in the mixture remains the same, CB derivatives seem to show improved chemical-physical features. In order to understand which factors account for their physical and chemical characteristics, and to check whether or not the obtained new matrices could be considered as valid alternatives to other vegetable fats (e.g., palm oil (PO)), we carried out an experimental investigation at both the macroscopic and molecular level including: (i) Differential Scanning Calorimetry (DSC) analyses to examine thermal features; (ii) rheological testing to explore mechanical properties; (iii) powder X-ray diffraction (PXRD) to evaluate the solid-state phases of the obtained fats; and (iv) 1H and 13C Nuclear Magnetic Resonance (NMR, 1D and 2D) spectroscopy to rapidly analyze fatty acid composition including regioisomeric distribution on the glycerol backbone. These last results open up the possibility of using NMR spectroscopy as an alternative to the chromatographic techniques routinely employed for the investigation of similar matrices.

Dynamic Properties of Di(cyclopentadienecarboxylic Acid) Dimethyl Esters.

Di(cyclopentadienecarboxylic acid) dimethyl ester (DCPDME) is a potential dynamic covalent system. When such molecules are used as dynamic crosslinkers in polymers, understanding the reversibility of cyclopentadiene dimerization is crucial to determine optimal melt processing conditions. To this end, we synthesized DCPDME, which consists of three regioisomers with different physicochemical properties, which were investigated by isolating them and further characterizing them using 1H NMR, FTIR and DSC. There have been many attempts to improve the synthesis process to increase the reaction yield and purity of isomer 3, and this goal remains a challenge today. In this work, we show that pure isomers 1 and 2 irreversibly convert to the more stable DCPDME isomer 3 at temperatures between 120 and 140 °C in N2. This shows that isolation of the pure isomer 3 from the DCPDME isomer mixture is not necessary. The DCPDME isomer 3 is reversibly cleaved to the monomeric cyclopentadienecarboxylic acid methyl ester (CPME), as confirmed with GC-MS and the resulting mass spectrum. The conversion of DCPDME isomers 1 and 2 to isomer 3 was confirmed by heating the synthesized mixture of DCPDME isomers at 135 °C for 5 min in N2, producing an almost pure isomer 3 which increased its synthesis yield by 35%.

Bioactive and Elastic Emulsion Electrospun DegraPol Tubes Delivering IGF-1 for Tendon Rupture Repair.

Tendon injuries can result in two major drawbacks. Adhesions to the surrounding tissue may limit the range of motion, while fibrovascular scar formation can lead to poor biomechanical outcomes. Prosthetic devices may help to mitigate those problems. Emulsion electrospinning was used to develop a novel three-layer tube based on the polymer DegraPol (DP), with incorporated insulin-like growth factor-1 (IGF-1) in the middle layer. Scanning electron microscopy was utilized to assess the fiber diameter in IGF-1 containing pure DP meshes. Further characterization was performed with Fourier Transformed Infrared Spectroscopy, Differential Scanning Calorimetry, and water contact angle, as well as through the assessment of mechanical properties and release kinetics from ELISA, and the bioactivity of IGF-1 by qPCR of collagen I, ki67, and tenomodulin in rabbit Achilles tenocytes. The IGF-1-containing tubes exhibited a sustained release of the growth factor up to 4 days and showed bioactivity by significantly upregulated ki67 and tenomodulin gene expression. Moreover, they proved to be mechanically superior to pure DP tubes (significantly higher fracture strain, failure stress, and elastic modulus). The novel three-layer tubes intended to be applied over conventionally sutured tendons after a rupture may help accelerate the healing process. The release of IGF-1 stimulates proliferation and matrix synthesis of cells at the repair site. In addition, adhesion formation to surrounding tissue can be reduced due to the physical barrier.

A Biopharmaceutical Perspective on Higher-Order Structure and Thermal Stability of mRNA Vaccines.

Preservation of the integrity of macromolecular higher-order structure is a tenet central to achieving biologic drug and vaccine product stability toward manufacturing, distribution, storage, handling, and administration. Given that mRNA lipid nanoparticles (mRNA-LNPs) are held together by an intricate ensemble of weak forces, there are some intriguing parallels to biologic drugs, at least at first glance. However, mRNA vaccines are not without unique formulation and stabilization challenges derived from the instability of unmodified mRNA and its limited history as a drug or vaccine. Since certain learning gained from biologic drug development may be applicable for the improvement of mRNA vaccines, we present a perspective on parallels and contrasts between the emerging role of higher-order structure pertaining to mRNA-LNPs compared to pharmaceutical proteins. In a recent publication, the location of mRNA encapsulated within lipid nanoparticles was identified, revealing new insights into the LNP structure, nanoheterogeneity, and microenvironment of the encapsulated mRNA molecules [Brader et al. Biophys. J. 2021, 120, 2766]. We extend those findings by considering the effect of encapsulation on mRNA thermal unfolding with the observation that encapsulation in LNPs increases mRNA unfolding temperatures.

New Saccharin Salt of Chlordiazepoxide: Structural and Physicochemical Examination.

Since the formation of organic salts can improve the solubility, bioavailability, and stability of active pharmaceutical ingredients, the aim of this work was to prepare an organic salt of chlordiazepoxide with saccharin. To achieve this goal, the saccharin salt of chlordiazepoxide was obtained from a physical mixture of both components by grinding them with a small volume of solvent and by crystallizing them with complete evaporation of the solvent. The resulting salt was examined by methods such as Powder X-ray Diffraction (PXRD), Single Crystal X-ray Diffraction (SCXRD), Differential Scanning Calorimetry (DSC), Thermogravimetric Analysis (TGA), Fourier Transform Infrared (FT-IR), and Raman spectroscopy. The results of the studies proved that saccharin salt of chlordiazepoxide crystallizes in the orthorhombic Pbca space group with one chlordiazepoxide cation and one saccharin anion in the asymmetric unit. In the crystal of the title compound, the chlordiazepoxide cation and the saccharin anion interact through strong N-H···O hydrogen bonds and weak C-H···O hydrogen bonds. The disappearance of the N-H band in the FT-IR spectrum of saccharin may indicate a shift of this proton towards chlordiazepoxide, while the disappearance of the aromatic bond band in the chlordiazepoxide ring in the Raman spectrum may suggest the formation of intermolecular hydrogen bonds between chlordiazepoxide molecules. The melting point of the salts differs from that of the starting compounds. Thermal decomposition of the salt begins above 200 °C and shows at least two overlapping stages of mass loss. In summary, the results of the research showed that the crystalline salt of the saccharin and chlordiazepoxide can be obtained by various methods: grinding with the addition of acetonitrile and crystallization from acetonitrile or a mixture of methanol with methylene chloride.

Low carbohydrate high fat flour: its rheology, bread making, physico-sensory and staling characteristics.

A low carbohydrate and high fat (LCHF) flour was developed by combining almond flour, desiccated coconut flour, defatted soya flour, dry gluten powder, psyllium husk and skimmed milk powder. Determination of rheological, bread making, nutritional, and staling characteristics of LCHF flour in comparison with wheat flour (WF) was studied. The results showed that LCHF flour had lower amylograph pasting temperature (31.6 °C), peak viscosity (200 BU), farinograph dough stability (0.8 min), and bread volume (315 ml) compared to WF (61.0 °C; 782 BU; 8.7 min; and 525 ml) respectively. The use of additive mixes such as fungal alpha-amylase, sodium stearoyl-2-lactylate and xanthan gum, improved the volume and texture of the LCHF bread. Scanning electron microscope images showed little or no presence of starch granules in LCHF dough and bread. Differential scanning calorimetry studies indicated that, during storage (1-5 days), the enthalpy for gelatinization of endotherm starch increased (0.71-3.40 j/g) in WF bread, however, in LCHF bread this increase was lesser (0.53 to 2.2 j/g) indicating slower staling rate in LCHF bread. The LCHF bread showed lower carbohydrate (13.7%), in-vitro starch digestibility (17.3%) and staling rate, higher protein (22.51%), fat (11.01%), and medium-chain fatty acids than WF bread (51.9%; 38.2%; 12.57%; 3.78%) respectively. The results showed that the developed product would be beneficial for people suffering from diabetics and obesity.

Blood serum denaturation profile examined by differential scanning calorimetry reflects the effort put into ultramarathon by amateur long-distance runners.

The impact of participation in the ultramarathon on the health and mental and physical condition is very complex. Undoubtedly, exercise brings many benefits but also involves health risks. Especially such an extreme effort as the one associated with finishing the ultramarathon run, can be dangerous to the health of the runner. With the variety of possible biomarkers of excessive fatigue that threaten health and life, a question arises which of them are the best and which should be considered in amateur long-distance runners showing particularly high individual variability. In this study differential scanning calorimetry (DSC) has been applied to show the overall effect of the 12-h run on blood sera of participants. Serum samples were obtained from the blood of ten male amateur long-distance runners, collected before and immediately after the run. Distinct changes in the shape of DSC curves have been observed for serum after finishing the run relative to pre-race serum. Statistically significant differences between stages "before" and "after" ultramarathon running have been found for parameters of the endothermic transition associated with denaturation of serum proteins. An increase in the temperature (from 70.9 ± 0.9 to 75.8 ± 2.9 °C) and excess heat capacity (from 0.859 ± 0.201 to 1.102 ± 0.226 Jg-1 °C-1) at peak maximum, the enthalpy of serum denaturation (from 18.55 ± 6.52 to 22.08 ± 5.61 Jg-1) and the first moment of the thermal transition with respect to the temperature (from the value of 67.0 ± 2.1 to 72.6 ± 2.1 °C) has been observed. These results show a clear impact of running an ultramarathon on the participant's blood serum.

Comprehensive Thermal Characteristics of Different Cultivars of Flaxseed Oil (Linum usittatissimum L.).

The aim of this study was to describe the thermal properties of selected cultivars of flaxseed oil by the use of the differential scanning calorimetry (DSC) technique. The crystallization and melting profiles were analyzed depending on different scanning rates (1, 2, 5 °C/min) as well as oxidative induction time (OIT) isothermally at 120 °C and 140 °C, and oxidation onset temperatures (Ton) at 2 and 5 °C/min were measured. The crystallization was manifested as a single peak, differing for a cooling rate of 1 and 2 °C/min. The melting curves were more complex with differences among the cultivars for a heating rate of 1 and 2 °C/min, while for 5 °C/min, the profiles did not differ, which could be utilized in analytics for profiling in order to assess the authenticity of the flaxseed oil. Moreover, it was observed that flaxseed oil was highly susceptible to thermal oxidation, and its stability decreased with increasing temperature and decreasing heating rate. Significant negative linear correlations were found between unsaturated fatty acid content (C18:2, C18:3 n-3) and DSC parameters (OIT, Ton). Principal component analysis (PCA) also established a strong correlation between total oxidation value (TOTOX), peroxide value (PV) and all DSC parameters of thermo-oxidative stability.

Isobavachalcone as an Active Membrane Perturbing Agent and Inhibitor of ABCB1 Multidrug Transporter.

Isobavachalcone (IBC) is an active substance from the medicinal plant Psoralea corylifolia. This prenylated chalcone was reported to possess antioxidative, anti-inflammatory, antibacterial, and anticancer activities. Multidrug resistance (MDR) associated with the over-expression of the transporters of vast substrate specificity such as ABCB1 (P-glycoprotein) belongs to the main causes of cancer chemotherapy failure. The cytotoxic, MDR reversing, and ABCB1-inhibiting potency of isobavachalcone was studied in two cellular models: human colorectal adenocarcinoma HT29 cell line and its resistant counterpart HT29/Dx in which doxorubicin resistance was induced by prolonged drug treatment, and the variant of MDCK cells transfected with the human gene encoding ABCB1. Because MDR modulators are frequently membrane-active substances, the interaction of isobavachalcone with model phosphatidylcholine bilayers was studied by means of differential scanning calorimetry. Molecular modeling was employed to characterize the process of membrane permeation by isobavachalcone. IBC interacted with ABCB1 transporter, being a substrate and/or competitive inhibitor of ABCB1. Moreover, IBC intercalated into model membranes, significantly affecting the parameters of their main phospholipid phase transition. It was concluded that isobavachalcone interfered both with the lipid phase of cellular membrane and with ABCB1 transporter, and for this reason, its activity in MDR cancer cells was presumptively beneficial.

Spray drying of naproxen and naproxen sodium for improved tableting and dissolution - physicochemical characterization and compression performance.

In this work, the tabletability and dissolution of spray-dried forms of naproxen and its sodium salt were compared with those of unprocessed drugs. Solutions of naproxen or naproxen sodium alone or with HPMC (5% w/w of drug content) were spray dried. Scanning electron micrographs showed that naproxen sodium spray-dried particles were spherical, whereas those of naproxen were non-spherical but isodiametric. Powder x-ray diffraction and thermal analysis indicated that co-spray drying with HPMC resulted in reduced crystallinity of naproxen and higher naproxen sodium dihydrate content. FTIR and Raman analysis showed shifting, merging or elimination of bands in the spectra of the co-spray dried products signifying solid-state alterations. When mixed with suitable processing aids (7% w/w), all co-spray dried powders produced satisfactory tablets in the pressure range 73-295 MPa. Conversely, physical mixtures of naproxen compressed with the same aids failed tableting, whereas naproxen sodium produced weak tablets. Dissolution tests showed significant improvement for co-spray dried drugs tablets. Therefore, since the large therapeutic doses of naproxen and sodium naproxen limit the use of tableting aids, the improved compaction and dissolution performance of the spray-dried forms may be a formulation alternative.

Thermodynamic Unfolding and Aggregation Fingerprints of Monoclonal Antibodies Using Thermal Profiling.

PURPOSE: Predicting thermal protein stability is of major interest in the development of protein-based biopharmaceuticals. Therefore, this study provides a predictive tool for determining transition enthalpies, which can be used for ranking different proteins according to their thermal stability. METHODS: Unfolding and aggregation profiles of eight different therapeutic monoclonal antibodies (mAbs) of type G, isotype 1 were investigated. The unfolding profiles were determined by intrinsic fluorescence (IF) spectroscopy and differential scanning calorimetry (DSC). A three-state unfolding fitting model was used to determine thermodynamic parameters for macromolecular multi-domain mAbs in IF experiments, like the van't Hoff enthalpy change (∆Hvh) and the entropy change (∆S) of the unfolding event. The derived values were compared to thermodynamic parameters obtained directly by calorimetry. Moreover, differences in the Fab enthalpies were used to predict aggregation behavior and protein thermal stabilities. To do so, the liquid-formulated mAbs were investigated exemplarily by size exclusion chromatography (SEC) after accelerated thermal-induced stress conditions. RESULTS: Comparing the thermodynamic parameters derived from IF spectroscopy and DSC resulted in similar values. Data generated by thermal-induced stress at 40°C show similar stability ranking as postulated through the Fab enthalpies for mAbs in two different formulations, while at 25°C a meaningful ranking is not possible, because distinct differences in the thermal stability cannot be observed. The additional consideration of Fab enthalpies to predict the 40 °C SEC ranking seems to be more reliable compared to the use of exclusively the melting temperatures or aggregation onset temperatures and times. CONCLUSION: We show that thermodynamic profiling can help predicting unfolding and aggregation properties of therapeutic mAbs at 40°C. Therefore, analyzing thermodynamic unfolding parameters is a useful and supportive tool discriminating thermal stability profiles of mAbs for further pharmaceutical development and clinical studies.

In-situ analysis of continuous cooling precipitation in Al alloys by wide-angle X-ray scattering.

The aim of this work is to investigate quench induced precipitation during continuous cooling in aluminium wrought alloys EN AW-7150 and EN AW-6082 using in situ synchrotron wide-angle X-ray scattering (WAXS). While X-ray diffraction is usually an ex situ method, a variety of diffraction patterns were recorded during the cooling process, allowing in situ analysis of the precipitation process. The high beam energy of about 100 keV allows the beam to penetrate a bulk sample with a 4 mm diameter in a quenching dilatometer. Additionally, the high intensity of a synchrotron source enables sufficiently high time resolution for fast in situ cooling experiments. Reaction peaks could be detected and compared with results from differential scanning calorimetry (DSC) by this method. A methodology is presented in this paper to evaluate WAXS data in a way that is directly comparable to DSC-experiments. The results show a high correlation between both techniques, DSC and WAXS, and can significantly improve continuous cooling precipitation diagrams.

Analysis and advanced characterization of municipal solid waste vermicompost maturity for a green environment.

Rapid demographic expansion along with increasing urbanization has aggravated the problem of solid waste management. Therefore, scientists are seeking waste management methods that are eco-friendly, cost effective and produce immediate results. In the developing world, municipal solid waste (MSW) contains mostly organic substances, therefore vermicomposting could be a better and cost-effective option for waste management. In this study, vermicomposting of organic portion of MSW with cow dung (additive) was performed using Eisenia fetida. The results showed significant (p < 0.001) decline in pH (13.17%), TOC (21.70%), C: N (62.53%) and C: P (57.66%) ratios, whilst total N (108.9%), P (84.89%) and K (21.85%) content increased (p < 0.001) in matured vermicompost. Different enzymatic activities declined during termination phase of vermicomposting experiment with maximum decrease of 41.72 (p = 0.002) and 39.56% (p = 0.001) in protease and ß-glucosidase, respectively. FT-IR, TGA, DSC and SEM studies suggested that final vermicompost was more stabilized as compared to initial waste mixture, characterized by reduced levels of aliphatic materials, carbohydrates and increase in aromatic groups possibly due to biosynthesis of humic substances. Both, the conventional (physicochemical and enzyme activity) and advanced techniques depict maturity and stability of the ready vermicompost. However, FT-IR, TGA, DSC and SEM were proved to be more promising, fast and reliable techniques over conventional analyses.