Solubilization Method Research Articles

Drug-Integrating Amphiphilic Nanomaterial Assemblies: 1. Spatiotemporal control of cyclosporine delivery and activity using nanomicelles and nanofibrils

Immunomodulatory therapies are limited by unavoidable side effects as well as poor solubility, stability, and pharmacokinetic properties. Nanomaterial-based drug delivery may overcome these limitations by increasing drug solubility, site-targeting, and duration of action. Here, we prepared innovative drug-integrating amphiphilic nanomaterial assemblies (DIANA) with tunable hydrophobicity, size, and morphology, and we evaluated their ability to deliver cyclosporine A (CsA) for immunomodulatory applications. We synthesized amphiphilic block copolymers made of poly(ethylene glycol)-poly(propylene sulfide) (PEG-PPS) and poly(ethylene glycol)-oligo(ethylene sulfide) (PEG-OES) that can self-assemble into solid core nanomicelles (nMIC, with ≈20 nm diameter) and nanofibrils (nFIB, with ≈5 nm diameter and > 500 nm length), respectively. nMIC and nFIB displayed good CsA encapsulation efficiency (up to 4.5 and 2 mg/mL, respectively in aqueous solution), superior to many other solubilization methods, and provided sustained release (>14 and > 7 days for the nMIC and nFIB) without compromising CsA's pharmacological activity. Treatment of insulin-secreting cells with unloaded DIANAs did not impair cell viability and functionality. Both CsA-loaded DIANAs inhibited the proliferation and activation of insulin-reactive cytotoxic T cells in vitro. Subcutaneous injections of CsA-loaded DIANAs in mice provided CsA sustained release, decreasing alloantigen-induced immune responses in the draining lymph node at lower doses and reduced administration frequency than unformulated CsA. While nMIC solubilized higher amounts and provided more sustained release of CsA in vitro, nFIB enhanced cellular uptake and promoted local retention due to slower trafficking in vivo. DIANAs provide a versatile platform for a local immune suppression regimen that can be applied to allogeneic cell transplantation.

Matrix-Bound Nanovesicles: The Effects of Isolation Method upon Yield, Purity, and Function.

Identification of matrix-bound nanovesicles (MBV) as ubiquitous components of the extracellular matrix (ECM) raises questions regarding their biologic functions and their potential theranostic application. Unlike liquid-phase extracellular vesicles (e.g., exosomes), MBV are tightly bound to the ECM, which makes their isolation and harvesting more challenging. The indiscriminate use of different methods to harvest MBV can alter or disrupt their structural and/or functional integrity. The objective of the present study was to compare the effect of various MBV harvesting methods upon yield, purity, and biologic activity. Combinations of four methods to solubilize the ECM (collagenase [COL], liberase [LIB], or proteinase K [PK] and nonenzymatic elution with potassium chloride) and four isolation methods (ultracentrifugation, ultrafiltration [UF], density barrier, and size exclusion chromatography [SEC]) were used to isolate MBV from urinary bladder-derived ECM. All combinations of solubilization and isolation methods allowed for the harvesting of MBV, however, distinct differences were noted. The highest yield, purity, cellular uptake, and biologic activity were seen with MBV isolated by a combination of liberase or collagenase followed by SEC. The combination of proteinase K and UF was shown to have detrimental effects on bioactivity. The results show the importance of selecting appropriate MBV harvesting methods for the characterization and evaluation of MBV and for analysis of their potential theranostic application. Impact statement Identification of matrix-bound nanovesicles (MBV) as ubiquitous components of the extracellular matrix (ECM) has raised questions regarding their biologic functions and their potential theranostic application. This study demonstrates that the harvesting methods used can result in samples with physical and biochemical properties that are unique to the isolation and solubilization methods used. Consequently, developing harvesting methods that minimize sample contamination with ECM remnants and/or solubilization agents will be essential in determining the theranostic potential of MBV in future studies.

Development of a Liposomal Dosage Form Based on Hydrophobic Derivative of Indolocarbazole

Introduction . An original N-glycoside derivative of indolocarbazole LHS-1269 with a carbohydrate xylose residue was synthesized at the N.N. Blokhin Russian Cancer Research Center Ministry of Health of Russia. It is characterized by high antitumor activity against a number of transferable ascitic and solid tumors in vivo experiments. Due to the hydrophobic properties of the substance LHS-1269, a method of solubilization by encapsulation in phospholipid vesicles - liposomes is proposed for creating an injectable dosage form. Aim . Development of the composition of a model of a liposomal dosage form for injection of an indolocarbazole derivative LHS-1269. Materials and methods . Substance LHS-1269 (N.N. Blokhin Russian Cancer Research Center Ministry of Health of Russia), egg phosphatidylcholine (PC, E PC S, Lipoid, Germany), cholesterol >99 % (Sigma-Aldrich, Japan), polyethylene glycol-2000-distearoylphosphatidylethanolamine (PEG-PE, Lipoid, Germany). To prepare phospholipid vesicles, the method of lipid film hydration with subsequent filtration and extrusion was used. The obtained liposomes were analyzed using the method of spectrophotometry, laser scattering spectroscopy, the method of determining the electrophoretic mobility of particles, and viscometry. Results and discussion . On the basis of lipid components and active substance in various molar ratios, compositions were made and experimental models of liposomal dispersion were obtained. The compositions were evaluated based on the effectiveness of LHS-1269 incorporation into liposomes and physical and chemical parameters - dispersion viscosity, vesicle size distribution, and zeta-potential. As a result of the analysis of 7 studied compositions, the optimal molar ratios of the drug form components - LHS-1269/PC 1:160 and PC/cholesterol/PEG-PE 1:0.33:0.003 were determined. The use of this composition allows us to obtain relatively stable (zeta-potential -33 mV) homogeneous liposomes with a diameter of 190 nm with a maximum level of encapsulation of the active substance of 98 %. Conclusions . As a result of technological and chemical-pharmaceutical research, the composition of a model of a liposomal dosage form for injection of the indolocarbazole derivative LHS-1269 has been developed.

Expression, Solubilization, Refolding and Final Purification of Recombinant Proteins as Expressed in the form of "Classical Inclusion Bodies" in E. coli.

Escherichia coli has been most widely used for production of the recombinant proteins. Over-expression of the recombinant proteins is the mainspring of the inclusion bodies formation. The refolding of these proteins into bioactive forms is cumbersome and partly time-consuming. In the present study, we reviewed and discussed most issues regarding the recovery of "classical inclusion bodies" by focusing on our previous experiences. Performing proper methods of expression, solubilization, refolding and final purification of these proteins, would make it possible to recover higher amounts of proteins into the native form with appropriate conformation. Generally, providing mild conditions and proper refolding buffers, would lead to recover more than 40% of inclusion bodies into bioactive and native conformation.

Subcritical Methanol Extraction of the Stone of Japanese Apricot Prunus mume Sieb. et Zucc.

The pits of Japanese apricot, Prunus mume Sieb. et Zucc., which are composed of stones, husks, kernels, and seeds, are unused by-products of the processing industry in Japan. The processing of Japanese apricot fruits generates huge amounts of waste pits, which are disposed of in landfills or, to a lesser extent, burned to form charcoal. Mume stones mainly consist of cellulose, hemicellulose, and lignin. Herein, we attempted to solubilize the wood-like carapace (stone) encasing the pit by subcritical fluid extraction with the aim of extracting useful chemicals. The characteristics of the main phenolic constituents were elucidated by liquid chromatography-mass spectrometry (LC-MS) and nuclear magnetic resonance (NMR) analyses. The degrees of solubility for various treatments (190 °C; 3 h) were determined as follows: subcritical water (54.9%), subcritical 50% methanol (65.5%), subcritical 90% methanol (37.6%), subcritical methanol (23.6%), and subcritical isopropyl alcohol (14.4%). Syringaldehyde, sinapyl alcohol, coniferyl alcohol methyl ether, sinapyl alcohol methyl ether, 5-(hydroxymethyl)-2-furfural, and furfural were present in the subcritical 90% methanol extract. Coniferyl and sinapyl alcohols (monolignols) are source materials for the biosynthesis of lignin, and syringaldehyde occur in trace amounts in wood. Our current findings provide a solubilization method that allows the main phenolic constituents of the pits to be extracted under mild conditions. This technique for obtaining subcritical extracts shows great potential for further applications.

Structural and therapeutic properties of curcumin solubilized pluronic F127 micellar solutions and hydrogels

Curcumin, the principle active constituent of turmeric, is known to have broad range of therapeutic properties. Its poor aqueous solubility and low bioavailability however, act as constraints for its biomedical applications. Recent studies have shown that incorporation of curcumin in nano-carriers like micelles, vesicles, polymeric nanoparticles etc. can help in overcoming these issues and improve its therapeutic abilities quite significantly. In this manuscript, we report preparation of curcumin solubilized pluronic F127 micellar solutions and hydrogels, along with their structural and therapeutic properties as obtained from SANS, rheological, anti-cancer and wound healing studies. Pluronic F127 being approved by FDA has been used quite extensively as excipient for drug delivery applications. Curcumin solubilization in the aqueous pluronic F127 system was carried out by briefly heating the copolymer solutions with curcumin at 90 °C. The concentrations of curcumin thus obtained were found to be comparable to those obtained by conventional methods of solubilization like thin film hydration or solvent evaporation method, and three orders of magnitude higher than that in pure water. SANS and rheological studies show that curcumin solubilization does not bring about any significant change in the structural and rheological properties of F127 micellar solutions and hydrogels. Curcumin solubilized F127 micellar solutions can be reconstituted after lyophilization, suggesting that curcumin remains nano-dispersed in lyophilized state. Micellar encapsulated curcumin exhibits very good stability in solution state in ambient condition but fails to show cytotoxicity against MCF7 cancer cells, presumably due to shielding of curcumin by large corona region of F127 micelles. Micellar curcumin containing F127 hydrogels on the other hand, exhibit wound healing abilities in mice model upon topical application. The results give an account of how some of the therapeutic properties of curcumin are manifested under micellar encapsulation and the role of pluronic F127 as excipient in those therapeutic applications.

PH-Controlled fermentation of strawberry waste as phenol solubilisation method

The present study aims to use pH as a control parameter for the accumulation of target compounds. Solubilisation of wasted strawberry through fermentation at different operational pH (pH 4, 7, and 9) was evaluated. Methane as a target compound was achieved at pH 7, reaching a value up to 353 ± 10 mL CH4/g VS (VS, volatile solids). Operation at pH 9 was hardly controlled due to the low pH of the substrate and the accumulation of VFA. pH 9 resulted in the highest accumulation of VFA, mainly acetic acid. The operation at pH 4 resulted in the inhibition of the biogas production, leading to the concentration of soluble phenols up to 3 times the initial concentration in the reactors. The concentrations of pelargonidin 3-glucoside and p-coumaric acid showed a significant increase at pH 4 (p = 0.157 and p = 0.058, respectively). Acidogenic fermentation could be a suitable method to solubilise bioactive compounds from wasted strawberries without the necessity of high-energy pre-treatments. The low energy demand, i.e. 19 equivalent kJ/g gallic acid, as well as the high phenol solubilisation capacity, indicates that the acidogenic fermentation at pH 4 it is a promising method for the recovery of phenols from wasted strawberry.

DirectMX - One-Step Reconstitution of Membrane Proteins From Crude Cell Membranes Into Salipro Nanoparticles.

Integral membrane proteins (IMPs) are central to many physiological processes and represent ∼60% of current drug targets. An intricate interplay with the lipid molecules in the cell membrane is known to influence the stability, structure and function of IMPs. Detergents are commonly used to solubilize and extract IMPs from cell membranes. However, due to the loss of the lipid environment, IMPs usually tend to be unstable and lose function in the continuous presence of detergent. To overcome this problem, various technologies have been developed, including protein engineering by mutagenesis to improve IMP stability, as well as methods to reconstitute IMPs into detergent-free entities, such as nanodiscs based on apolipoprotein A or its membrane scaffold protein (MSP) derivatives, amphipols, and styrene-maleic acid copolymer-lipid particles (SMALPs). Although significant progress has been made in this field, working with inherently unstable human IMP targets (e.g., GPCRs, ion channels and transporters) remains a challenging task. Here, we present a novel methodology, termed DirectMX (for direct membrane extraction), taking advantage of the saposin-lipoprotein (Salipro) nanoparticle technology to reconstitute fragile IMPs directly from human crude cell membranes. We demonstrate the applicability of the DirectMX methodology by the reconstitution of a human solute carrier transporter and a wild-type GPCR belonging to the human chemokine receptor (CKR) family. We envision that DirectMX bears the potential to enable studies of IMPs that so far remained inaccessible to other solubilization, stabilization or reconstitution methods.

Measuring Membrane Protein-Lipid Interactions in Nanodiscs with Native Mass Spectrometry

Native mass spectrometry (MS), which uses nondenaturing ionization to preserve noncovalent complexes for mass analysis, has proven to be powerful for characterizing membrane protein complex stoichiometry and interactions. Membrane proteins are traditionally solubilized using detergent micelles prior to native MS. Collisional activation is employed in the mass spectrometer to remove bound detergent and yield the membrane protein, potentially in complex with bound lipids. However, this method of solubilization can be problematic as detergents may distort the native-like structure and function of membrane proteins. Furthermore, the collisional activation required for detergent removal can lead to the loss of noncovalent interactions within fragile complexes. Lipoprotein nanodiscs provide a more natural lipid bilayer environment for delivering membrane proteins for native MS, but previous measurements have been limited by the moderate stability of nanodiscs in the gas phase. It is difficult to preserve the intact membrane protein-nanodisc complex for native MS but also difficult to efficiently eject membrane proteins from nanodiscs. To tune the stability of nanodiscs, we used chemical additives known to modulate the charge acquired during electrospray ionization (ESI). Two membrane proteins, the trimeric ammonium transporter AmtB and tetrameric aquaporin ApqZ, were reconstituted into nanodiscs for native MS. Employing charge manipulation reagents and different ionization polarities allowed us to either capture the intact membrane protein-nanodisc complex or eject the membrane protein with few bound lipids. We are currently investigating the selectivity of lipid binding to membrane proteins ejected from nanodiscs of mixed lipid compositions. Preliminary results show that distinct lipid shells corresponding to different types of protein-lipid interactions are preferentially enriched in either zwitterionic or anionic lipids. Ultimately, we expect our novel methods combining native MS and nanodiscs will provide unique insights into membrane protein-lipid interactions in model lipid bilayers.

Potential use of human hair shaft keratin peptide signatures to distinguish gender and ethnicity.

BackgroundMost human hairs collected at old crime scenes do not contain nuclear DNA and are therefore of less value for forensic investigations. In the present study, hair shaft proteins were extracted from 40 healthy subjects between the ages of 21 to 40 years and profiled using gel electrophoresis-based proteomics to determine if they can be used to distinguish gender and ethnicity.MethodsExtraction of the human hair shaft proteins was performed using a newly developed alkaline solubilisation method. The extracts were profiled by 2-dimensional electrophoresis and resolved protein spots were identified by mass spectrometry and queried against the human hair database. The study was then followed-up by immunoblotting of the identified hair shaft keratin of interest using commercially available antibodies.ResultsSeparation of the human hair shaft proteins by 2-dimensional electrophoresis generated improved and highly resolved profiles. Comparing the hair shaft protein profiles of 10 female with 10 male subjects and their identification by mass spectrometry and query of the human hair database showed significant altered abundance of truncated/processed type-II keratin peptides K81 (two spots), K83 (one spot) and K86 (three spots). The 2-dimensional electrophoresis profiling of 30 hair shaft samples taken from women of similar age range but from three distinctive ethnic subpopulations in Malaysia further showed significant altered abundance of one type-I and four type-II truncated/processed keratin peptides including K33b, K81, K83 and K86 (2 spots) between at least two of the ethnic groups. When a followed-up immunoblotting experiment was performed to detect the relative expression of the K86 peptides using commercialised antibodies, similar trends of expression were obtained. The present data, when taken together, demonstrated the potential use of keratin peptide signatures of the human hair shaft to distinguish gender and ethnicity although this needs to be further substantiated in a larger scale study.

Recovery of inclusion body protein in Escherichia coli: Effects of solubilization methods and process condition

Inclusion bodies (IBs) are produced in Escherichia coli cells and solubilization process is required to recover desired protein in bioactive form. Conventional and mild solubilization methods were applied for IBs solubilization and the performances were influenced by respective process condition. Therefore, it is the objective of current work to investigate the effects of solubilization methods on the recovery of soluble enhanced green fluorescent protein (EGFP) from IBs by using urea, alkyl alcohol and freeze thaw method. The present study indicates urea concentration, incubation temperature, type of alcohol and its concentration, freezing duration and freeze thaw cycles influenced the yield and purity of solubilized EGFP. Conventional method using 8 M of urea with incubation temperature of 60°C achieved the highest yield (61%) and purity (10%). Mild IBs solubilization with 6 M of n-butanol and 2 M of urea has solubilized IBs with a yield of 45% and purity of 22%. By freezing and thawing the IBs suspension in 2 M of urea, the yield (66%) and purity (9%) of solubilized EGFP were comparable to that of 8 M of urea in buffer. Hence, mild solubilization using the alkyl alcohol or freeze thaw method is applicable for IBs solubilization.

GPCR Solubilization and Quality Control.

G protein-coupled receptors (GPCRs) are versatile membrane proteins involved in the regulation of many physiological processes and pathological conditions, making them interesting pharmacological targets. In order to study their structure and function, GPCRs are traditionally extracted from membranes using detergents. However, due to their hydrophobic nature, intrinsic instability in aqueous solutions, and theirdenaturing effects, theisolation of properly folded and functional GPCRs is not trivial. Therefore, it is of crucial importance to solubilize receptors under mild conditions and control the sample quality subsequently. Here we describe widely used methods for small-scale GPCR solubilization, followed by quality control based on fluorescence size-exclusion chromatography, SDS-PAGE, temperature-induced protein unfolding (CPM dye binding) and fluorescent ligand binding assay. These methods can easily be used to assess the thermostability and functionality of a GPCR sample exposed to different conditions, such as theuse of various detergents, addition of lipids and ligands, making them valuable for obtaining an optimal sample qualityfor structural and functional studies.

Método de Solubilização Alcalina Aplicado à Amostras de Pão Industrializado Para Subsequente Determinação de Cu, Fe, K, Mg, Na e Zn Por Espectrometria Atômica

Foi desenvolvido um metodo de preparo de amostras de pao do tipo bisnaguinha utilizando o TMAH para a solubilizacao alcalina. O objetivo desse trabalho foi avaliar a concentracao de Cu, Fe, K, Mg, Na e Zn apos a solubilizacao das amostras a temperatura ambiente, em overnight. A solubilizacao alcalina se apresentou como um metodo simples e rapido, alem de ser uma melhor alternativa frente aos procedimentos de mineralizacao convencional, permitindo a solubilizacao completa das amostras usando pequenas quantidades de TMAH. Utilizou-se um metodo de decomposicao acida e adicao de analito para avaliar a exatidao do metodo. Obtiveram-se baixos limites de deteccao 0,073; 0,051; 0,021; 0,008; 0,003 e 0,043 mg kg-1 para Cu, Fe, K, Mg, Na e Zn, respectivamente, alem de bons valores de recuperacao, variando de 80 a 120 % para os analitos. Dentre os resultados obtidos todos apresentaram concentracoes de acordo com a legislacao pra Na e abaixo do DRI para os demais mais elementos. A comparacao de metodo nao apresentou diferenca significativa, assim o metodo se mostrou adequado para as analises.

Removal of ammonia from chicken manure by ultra-high temperature solubilization method

Removal of ammonia from chicken manure by ultra-high temperature solubilization method

Effects of pressure-assisted enzymatic hydrolysis on functional and bioactive properties of tilapia (Oreochromis niloticus) by-product protein hydrolysates

Fish by-product protein can be converted into valuable food and nutraceutical ingredients via proteolysis. The existing process suffers from many limitations such as extended reaction time and nonselective hydrolysis. In this study, protein from tilapia fish by-products was transformed into functional peptides using pressure-assisted enzymatic hydrolysis. Proteins were extracted from the tilapia by-products by isoelectric solubilization and precipitation method. The effects of pressure (38–462 MPa) and hydrolysis time (6–35 min) on the properties of the hydrolysates were investigated using a central composite design. Pressure enhanced protein hydrolysis with a maximum trichloroacetic acid-solubility index (TCA-SI) of 23% obtained at 250 MPa for 35 min. Pressure and time were also vital in improving soluble protein content (5.7 mg/mL), reducing power (44 μg AAE/g), and solubility (71%) of the hydrolyzed products. Improved antioxidant activity, indicated by a significant decrease in IC50 values from 653 μg/mL to 304 μg/mL, was recorded. The combined process facilitated the release of low-molecular-weight peptides and essential amino acids. However, water and oil holding capacities were found to be decreased. Pressure-assisted enzymatic hydrolysis could provide an effective approach for recovering bioactive peptides from fish by-products for industrial applications.

Aqueous Solubility Enhancement and Thermodynamic Aggregation Behavior of Resveratrol Using an Eco-Friendly Hydrotropic Phenomenon

Resveratrol, a stilbenoid polyphenol compound found in the skin and seeds of black grapes, which is supposed to have biological activity as an anti-inflammatory, anti-tumor, and anti-aging agent. Low oral bioavailability of resveratrol is determined by its low solubility in water. To overcome this, a biocompatible solubilization method is used to intensify the solubility of resveratrol. Hydrotropes (solubilizing agents) such as sodium caprylate, and sodium benzoate under a wide range of concentrations (0‒3 mol/L) and temperature (303–333 K) were used to study the aqueous solubility of resveratrol. It is observed that the solubility of resveratrol is enhanced by 16 times in the presence of sodium caprylate as hydrotrope. Thermodynamic properties like entropy, Gibbs free energy, and enthalpy were determined, and the solubilization process was found to be entropy-driven.

Toxicity of dextran stabilized fullerene C60 against C6 Glial cells

Elevated application potential of fullerene C60 paved the way to think on its adverse effect when it reaches to biological system and environment. Though fullerenes are insoluble in water, various strategies are employed to make it soluble. Method of solubilization with organic solvents, yield cytotoxic responses both in vitro and in vivo. In this study, dextran was used to stabilize C60 particle. Fourier transformed-infrared spectroscopy (FT-IR) and transition electron microscopy (TEM) were used for characterization and it confirms effective surface stabilization and morphological characteristics. This was followed by various cytotoxicity studies to evaluate its bio-nano interactions. The results of the study suggest that the dextran stabilized C60 nanoparticles (Dex-C60) forms uniform suspension in water and was stable up to 72 h. The C6 glial cell-Dex-C60 interactions indicated that the Dex-C60 nanoparticles penetrate deeper into the cells and cause dose dependent toxic response. The result of the study recommended that Dex-C60 nanoparticles should undergo intensive risk assessment before biomedical applications and should take proper safety measure to avoid its entry to the environment.

Proteomics analysis of the matrisome from MC38 experimental mouse liver metastases.

Dissemination of primary tumors to distant anatomical sites has a substantial negative impact on patient prognosis. The liver is a common site for metastases from colorectal cancer, and patients with hepatic metastases have generally much shorter survival, raising a need to develop and implement novel strategies for targeting metastatic disease. The extracellular matrix (ECM) is a meshwork of highly crosslinked, insoluble high-molecular-mass proteins maintaining tissue integrity and establishing cell-cell interactions. Emerging evidence identifies the importance of the ECM in cancer cell migration, invasion, intravasation, and metastasis. Here, we isolated the ECM from MC38 mouse liver metastases using our optimized method of mild detergent solubilization followed by biochemical enrichment. The matrices were subjected to label-free quantitative mass spectrometry analysis, revealing proteins highly abundant in the metastatic matrisome. The resulting list of proteins upregulated in the ECM significantly predicted survival in patients with colorectal cancer but not other cancers with strong involvement of the ECM component. One of the proteins upregulated in liver metastatic ECM, annexin A1, was not previously studied in the context of cancer-associated matrisome. Here, we show that annexin A1 was markedly upregulated in colon cancer cell lines compared with cancer cells of other origin and also over-represented in human primary colorectal lesions, as well as hepatic metastases, compared with their adjacent healthy tissue counterparts. In conclusion, our study provides a comprehensive ECM characterization of MC38 experimental liver metastases and proposes annexin A1 as a putative target for this disease.NEW & NOTEWORTHY Here, the authors provide an extensive proteomics characterization of murine colorectal cancer liver metastasis matrisome (the ensemble of all extracellular matrix molecules). The findings presented in this study may enable identification of therapeutic targets or biomarkers of hepatic metastases.

S-rGO/ZnS nanocomposite-mediated photocatalytic pretreatment of dairy wastewater to enhance aerobic digestion

The treatment of real dairy wastewater by aerobic digestion is a time taking process due to the complex nature of organics present in dairy effluent. Herein, solar light-mediated photocatalytic pretreatment of the dairy wastewater was performed to decompose the complexed organic into shorter chair organics. The sulfur-doped reduced graphene oxide/zinc sulfide (S-rGO/ZnS) nanocomposite was applied as an efficient photocatalyst to solubilize and decompose the organic components in dairy wastewater under natural solar light. The results showed that the photocatalytic treatment enhanced the solubilized chemical oxygen demand (SCOD) by 113% after 6 h of sunlight exposure as compared to 28.1% of SCOD under the photolysis conditions. The aerobic digestion of the pretreated dairy wastewater showed 94% removal of total chemical oxygen demand (TCOD) after 36 days. TCOD of pretreated and untreated dairy wastewater was decreased to the level 71mg/L and 257mg/L after the aerobic digestion, indicating the effectiveness of the pretreatment process. A water quality analysis of photocatalysis-aerobic treatment showed that the values for various parameters such as COD, total solids, nitrogen, alkalinity, oil and grease content, electrical conductivity and pH were at acceptable limits for environmental discharge of dairy effluent. This study reveals that photocatalytic pretreatment of dairy wastewater is an effective method for solubilization of the complex organic components of dairy effluents which can be easily decomposed by the microbes during the aerobic digestion process.

Ketoconazole solubility in aqueous binary mixtures of 1‑propanol at various temperatures

The aim of this work is to have a brief overview on various solubilization methods reported for ketoconazole and using a commonly used method, i.e. cosolvency for enhancement of ketoconazole in binary mixtures of 1‑propanol and water at different temperatures. The generated data are correlated with eight cosolvency mathematical models including the van't Hoff, the double log-log, the mixture response surface, Yalkowsky, Jouyban-Acree, Jouyban-Acree-van't Hoff, modified Jouyban-Acree-van't Hoff, and the modified Wilson models. The mean relative deviations (MRD%) of the back-calculated solubility for each investigated models are calculated as an accuracy criterion. Density of the ketoconazole saturated solutions as another physico-chemical properties is also fitted by the Jouyban-Acree model. Moreover, standard enthalpy, entropy and Gibbs free energy change for ketoconazole dissolution process were obtained by using van't Hoff and Gibbs equations. Finally, preferential solvation analysis based on the inverse Kirkwood-Buff integrals demonstrates that ketoconazole is preferentially solvated by water in water-rich mixtures but preferentially solvated by 1‑propanol in mixtures of 0.19 < x1 < 1.00.