Mechanism Of Solubilization Research Articles

Sorption of water–ethanol mixtures by poplar wood: swelling and viscoelastic behaviour

The swelling of wood upon impregnation by aqueous solutions of organic solvents is larger than swelling by pure water. This phenomenon, described as “hyperswelling”, results from specific interactions with components of the complex wood microstructure. To understand the combined effect of mixed solvents on wood properties, the specific influence of each solvent on wood biopolymers and structure must be first characterized. In this study, the effect of the impregnation of aqueous solutions of ethanol with concentrations from 0 to 100% on the physico-mechanical properties of poplar wood was investigated. For each solution, the sorption behaviour of veneer sapwood samples and the effect of sorption on wood viscoelasticity and microstructure were measured through vapour sorption gravimetry, dynamic mechanical analysis and optical microscopy monitoring. Pure water and pure ethanol showed contrasting sorption behaviour, ethanol leading to a much lower swelling and a very limited softening compared to water, despite comparable sorbed amounts. This result suggests different affinities of water and ethanol for biopolymers within wood microstructure. With mixed solutions, larger swelling and stronger variations in viscoelastic behaviour than in pure solvents were observed, confirming the synergistic effect of water/ethanol mixtures on structure and properties of wood cells. Microscopic observations evidenced that ethanol, both alone and in aqueous solutions, generates intercellular decohesion and disbonding of the different wood cell wall layers. These observations are consistent with a mechanism of partial solubilization by ethanol of lignin-related phenolic. This could lead to a release of the constraints which limit the swelling of the polysaccharide fraction of the cell wall by water. Such phenomenon is likely to be at the origin of the hyperswelling observed in mixed water/organic solvent systems.

Isolation and characterization of phosphofungi, and screening of their plant growth-promoting activities

Rhizospheric microorganisms can increase phosphorus availability in the soil. In this regard, the ability of phosphofungi to dissolve insoluble phosphorus compounds is greater than that of phosphate-solubilizing bacteria. The aim of the current study was to identify efficient phosphofungi that could be developed as commercial microbial agents. Among several phosphate-solubilizing fungal isolates screened, strain CS-1 showed the highest phosphorus-solubilization ability. Based on phylogenetic analysis of the internal transcribed spacer region sequence, it was identified as Aspergillus niger. High-performance liquid chromatography analysis revealed that the mechanism of phosphorus solubilization by CS-1 involved the synthesis and secretion of organic acids, mainly oxalic, tartaric, and citric acids. Furthermore, strain CS-1 exhibited other growth-promoting abilities, including efficient potassium release and degradation of crop straw cellulose. These properties help to returning crop residues to the soil, thereby increasing nutrient availability and sustaining organic matter concentration therein. A pot experiment revealed that CS-1 apparently increased the assessed biometric parameters of wheat seedlings, implying the potential of this strain to be developed as a commercial microbial agent. We used Illumina MiSeq sequencing to investigate the microbial community composition in the rhizosphere of uninoculated wheat plants and wheat plants inoculated with the CS-1 strain to obtain insight into the effect of the CS-1 strain inoculation. The data clearly demonstrated that CS-1 significantly reduced the content of pathogenic fungi, including Gibberella, Fusarium, Monographella, Bipolaris, and Volutella, which cause soil-borne diseases in various crops. Strain CS-1 may hence be developed into a microbial agent for plant growth improvement.

Combined UV–Vis-absorbance and reflectance spectroscopy study of dye transfer kinetics in aqueous mixtures of surfactants

We report an analytical approach to study the competitive processes of solubilisation in micelles and of adsorption onto hydrophobic surfaces of poorly soluble hydrophobic dyes. The method is demonstrated on model systems containing two sources of Disperse Red 60: a bulk powder and a donor red textile, with molecularly dissolved dye stabilised in an aqueous environment by mixed micelles of anionic and non-ionic surfactants. The process of dye transfer between a donor textile (red polyester), surfactant micelles and an acceptor textile (white polyamide) was quantified by a combination of colorimetric analyses. UV–Vis absorbance was used to follow the extraction of the dye and to evaluate the solubilisation capacity of the micellar solution. A calibration curve for textile reflectance versus the adsorbed dye was generated to quantify the mass of dye transferred onto the acceptor textile. A combination of both techniques allowed us to compare the amount of dye desorbed from the donor textile and adsorbed onto the acceptor textile as a function of time for systems undergoing exhaustion-solubilisation mechanisms and only solubilisation mechanism. Up to ≃10 min of the washing process, the released dye is predominantly solubilised in surfactant micelles. At later times, the adsorption of the dye on the hydrophobic surface is energetically favoured. The shift of the desorption equilibrium in the presence of the acceptor textile results in ≃30% increase in the release of the dye. The reported methodology provides direct comparative analysis between the solubilisation capacity of amphiphilic stabilisers and the tendency of the dye to adsorb on solid substrates, important for designing novel concepts of disperse dye solubilisation and dye transfer inhibition during textile washing.

Predictive Modeling of Micellar Solubilization by Single and Mixed Nonionic Surfactants

Micellar solubilization is an important concept in the delivery of poorly water-soluble drugs. The rational selection of the type and the amount of surfactant to be incorporated in a formulation require comprehensive solubility studies. These studies are time and material demanding, both of which are scarce, especially during late discovery and early development stages. We hypothesized that, if the solubilization mechanism or molecular interaction is similar, the solubilization capacity ratio (a newly defined parameter) is dictated by micellar structures, independent of drugs. We tested this hypothesis by performing solubility studies using 8 commonly used nonionic surfactants and 17 insoluble compounds with diverse characteristics. The results show a striking constant solubilization capacity ratio among the 8 nonionic surfactants, which allow us to develop predictive solubility models for both single and mixed surfactant systems. The vast majority of the predicted solubility values, using our developed models, fall within 2-fold of the experimentally determined values with high correlation coefficients. As expected, systems involving ionic surfactant sodium dodecyl sulfate, used as a negative control, do not follow this trend. Deviations from the model, observed in this study or envisioned, were discussed. In conclusion, we have established predictive models that are capable of predicting solubility in a wide range of nonionic micellar solutions with only 1 experimental measurement. The application of such a model will significantly reduce resource and greatly enhance drug product development efficiency.

Strain Serratia sp. S119: A potential biofertilizer for peanut and maize and a model bacterium to study phosphate solubilization mechanisms

Strain Serratia sp. S119 is a peanut native bacterium with high phosphate solubilizing activity that promotes the growth of peanut and maize in the cultivation area of Córdoba in Argentina. The aims of this study were to obtain and analyze the genome sequence of Serratia sp. S119 to understand the genetic basis of its beneficial properties on plant growth, and to demonstrate phosphate solubilizing ability in early stages of bacterial growth. Results obtained indicated that soluble P and gluconic acid were detected during exponential growth phase in bacterial supernatant. Analysis of the genome sequence of Serratia sp. S119 obtained from this study showed the presence of genes related to several plant growth promoting traits. The genome sequence of this strain is a valuable source of information to study bacterial response to phosphate starvation and to investigate interaction between this bacterium with host plants under nutritional deficient environments.

Mechanistic insights into the role of prenyl-binding protein PrBP/\u03b4 in membrane dissociation of phosphodiesterase 6

Isoprenylated proteins are associated with membranes and their inter-compartmental distribution is regulated by solubilization factors, which incorporate lipid moieties in hydrophobic cavities and thereby facilitate free diffusion during trafficking. Here we report the crystal structure of a solubilization factor, the prenyl-binding protein (PrBP/δ), at 1.81 Å resolution in its ligand-free apo-form. Apo-PrBP/δ harbors a preshaped, deep hydrophobic cavity, capacitating apo-PrBP/δ to readily bind its prenylated cargo. To investigate the molecular mechanism of cargo solubilization we analyzed the PrBP/δ-induced membrane dissociation of rod photoreceptor phosphodiesterase (PDE6). The results suggest that PrBP/δ exclusively interacts with the soluble fraction of PDE6. Depletion of soluble species in turn leads to dissociation of membrane-bound PDE6, as both are in equilibrium. This “solubilization by depletion” mechanism of PrBP/δ differs from the extraction of prenylated proteins by the similar folded solubilization factor RhoGDI, which interacts with membrane bound cargo via an N-terminal structural element lacking in PrBP/δ.

Phosphate-solubilizing fungi for efficient soil phosphorus management

Rhizosphere soil extracts obtained from eight cinnamon species and three pepper species cultivated organically were inoculated initially on Pikovskaya (PVK) medium. The twelve fungal isolates that solubilized the insoluble phosphates were further tested on the same medium added with both insoluble tricalcium phosphate and soluble dipotassium hydrogen phosphate to detect the expression of the trait in the presence of soluble phosphates in soil, for which all twelve qualified. The efficiencies of phosphate solubilization were investigated in two liquid media: PVK medium to represent soil phosphate pool and a rock phosphate (RP) medium, by determining the available phosphorus concentration in the liquid media at the end of the 24 h and 72 h incubation periods, respectively. The pH reduction in the medium was measured to ascertain the organic acid production by fungal isolates as a mechanism of solubilization. Three fungal isolates showing the highest efficiencies in phosphate solubilization were taxonomically identified based on the micromorphological characteristics and molecular techniques. Two isolates were identified as Penicillium oxalicum and Trichorderma virens and the other was belonging to the genus Aspergillus. A possible synergism between the three fungal species towards phosphate dissolution was detected using the broth culture procedure. Aspergillus sp. in combination with P. oxalicum dissolved both Ca3(PO4)2 and RP recording the highest significant dissolved phosphate levels of 893.43 (±56.768) mg P/L and 309.42 (±42.52) mg P/L, respectively, within 72 h post inoculation, making them prospective candidates for increased phosphate availability of soil phosphate pool and rock phosphates.

Dicationic hydroxylic surfactants: Aggregation behavior, guest-host interaction and catalytic effect

Herein, supramolecular systems with improved aggregation, solubilization and catalytic activity have been constructed by self-assembly of gemini surfactants with two cationic centers separated by the spacer chain of 10 atoms long and hydroxyl functionality in their head group or in the spacer. It was found that hydroxylic dicationic surfactants capable of forming hydrogen bonds exhibit the ability to micelle formation at a concentration substantially lower than that of their monocationic and non-functionalized dicationic counterparts. They are capable of initiating additional solubilization mechanisms, which are responsible for the enhanced solubilization capacity of the surfactants. The use of the dicationic hydroxylic surfactants in hydrolytic decomposition of esters gives rise to the high catalytic effect and substrate selectivity: the highest, 430-fold, acceleration was observed for p-nitrophenyl caprate.

Polymorphic transformation as a result of atovaquone incompatibility with selected excipients

Differential scanning calorimetry (DSC), Fourier transform infrared spectroscopy, and hot-stage microscopy were employed to evaluate the drug–excipient compatibility of atovaquone with commonly used tablet excipients. The DSC curves of pure drug and excipients were compared with their physical mixtures. Microcrystalline cellulose, titanium dioxide, colloidal silica, ferric oxide, lactose monohydrate, and sodium starch glycolate were compatible, while magnesium stearate, polyethylene glycol (PEG) 8000, Poloxamer 188, and hydroxypropyl methyl cellulose (HPMC) E15 showed incompatibility with the drug. Heat–cool–heat analysis of the physical and the ground mixture of later three excipients showed polymorphic transformation of atovaquone form III to form I, which occurred via amorphization with HPMC E15 and through solubilization mechanism with remaining two excipients. These outcomes were further supported by hot-stage microscopy. Results of milling experiments revealed a milling time-dependent polymorphic transformation and solubilization with HPMC E15 and PEG 8000, respectively. This study highlights the importance of compatibility assessment for selection of excipients in specific unit operations such as milling and grinding.

Investigation of parameters and mechanism of ultrasound-assisted wet reclamation of waste sodium silicate sands

In this paper, an ultrasound method was applied in the wet reclamation process, and the feasibility and parameters of the ultrasound-assisted wet reclamation were studied, and the mechanism of the ultrasonic solubilization was also analyzed. The effects of ultrasonic power, time, water consumption, and reclamation times on the de-skinning rate were systematically investigated. The results indicated that the ultrasonic-assisted wet reclamation of the waste sodium silicate sands was feasible. The ultrasonic mechanical effect, cavitation, and thermal effect could accelerate the dissolution of the sodium silicate and improve the de-skinning rate significantly. Orthogonal experiment analysis showed that increasing the ultrasonic power, prolonging the time as well as increasing the water consumption could improve the de-skinning rate. Under the condition of the low water consumption, the de-skinning rate of the ultrasound-assisted wet reclamation reached 90.58%, while the total water consumption was 0.9 t for 1 t of the waste sodium silicate sands.

Identification of Heterotrophic Zinc Mobilization Processes among Bacterial Strains Isolated from Wheat Rhizosphere (Triticum aestivum L.).

Soil and plant inoculation with heterotrophic zinc-solubilizing bacteria (ZSB) is considered a promising approach for increasing zinc (Zn) phytoavailability and enhancing crop growth and nutritional quality. Nevertheless, it is necessary to understand the underlying bacterial solubilization processes to predict their repeatability in inoculation strategies. Acidification via gluconic acid production remains the most reported process. In this study, wheat rhizosphere soil serial dilutions were plated on several solid microbiological media supplemented with scarcely soluble Zn oxide (ZnO), and 115 putative Zn-solubilizing isolates were directly detected based on the formation of solubilization halos around the colonies. Eight strains were selected based on their Zn solubilization efficiency and siderophore production capacity. These included one strain of Curtobacterium, two of Plantibacter, three strains of Pseudomonas, one of Stenotrophomonas, and one strain of Streptomyces In ZnO liquid solubilization assays, the presence of glucose clearly stimulated organic acid production, leading to medium acidification and ZnO solubilization. While solubilization by Streptomyces and Curtobacterium was attributed to the accumulated production of six and seven different organic acids, respectively, the other strains solubilized Zn via gluconic, malonic, and oxalic acids exclusively. In contrast, in the absence of glucose, ZnO dissolution resulted from proton extrusion (e.g., via ammonia consumption by Plantibacter strains) and complexation processes (i.e., complexation with glutamic acid in cultures of Curtobacterium). Therefore, while gluconic acid production was described as a major Zn solubilization mechanism in the literature, this study goes beyond and shows that solubilization mechanisms vary among ZSB and are strongly affected by growth conditions.IMPORTANCE Barriers toward a better understanding of the mechanisms underlying zinc (Zn) solubilization by bacteria include the lack of methodological tools for isolation, discrimination, and identification of such organisms. Our study proposes a direct bacterial isolation procedure, which prevents the need to screen numerous bacterial candidates (for which the ability to solubilize Zn is unknown) for recovering Zn-solubilizing bacteria (ZSB). Moreover, we confirm the potential of matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) as a quick and accurate tool for the identification and discrimination of environmental bacterial isolates. This work also describes various Zn solubilization processes used by wheat rhizosphere bacteria, including proton extrusion and the production of different organic acids among bacterial strains. These processes were also clearly affected by growth conditions (i.e., solid versus liquid cultures and the presence and absence of glucose). Although highlighted mechanisms may have significant effects at the soil-plant interface, these should only be transposed cautiously to real ecological situations.

Solubilization of the serotonin1A receptor monitored utilizing membrane dipole potential

Solubilization of membrane proteins by amphiphilic detergents represents a crucial step in studies of membrane proteins in which proteins and lipids in natural membranes are dissociated giving rise to mixed clusters of proteins, lipids and detergents in the aqueous dispersion. Although solubilization is a popular method, physicochemical principles underlying solubilization are not well understood. In this work, we monitored solubilization of the bovine hippocampal serotonin1A receptor, a representative member of the GPCR family, using membrane dipole potential measured by a dual fluorescence ratiometric approach with a potential-sensitive fluorophore. Our results show that membrane dipole potential is a good indicator of solubilization and reflects the change in dipolar environment upon solubilization due to dipolar reorganization associated with solubilization. To the best of our knowledge, these results constitute the first report linking membrane dipole potential with solubilization. We envision that these results are potentially useful in providing a molecular mechanism for membrane protein solubilization.

Effect of organic acids production and bacterial community on the possible mechanism of phosphorus solubilization during composting with enriched phosphate-solubilizing bacteria inoculation

Enriched phosphate-solubilizing bacteria (PSB) agent were acquired by domesticated cultivation, and inoculated into kitchen waste composting in different stages. The effect of different treatments on organic acids production, tricalcium phosphate (TCP) solubilization and their relationship with bacterial community were investigated during composting. Our results pointed out that inoculation affected pH, total acidity and the production of oxalic, lactic, citric, succinic, acetic and formic acids. We also found a strong advantage in the solubilization of TCP and phosphorus (P) availability for PSB inoculation especially in the cooling stage. Redundancy analysis and structural equation models demonstrated inoculation by different methods changed the correlation of the bacterial community composition with P fractions as well as organic acids, and strengthened the cooperative function related to P transformation among species during composting. Finally, we proposed a possible mechanism of P solubilization with enriched PSB inoculation, which was induced by bacterial community and organic acids production.

Phenotypic and genotypic characterization of phosphate solubilizing bacteria and their efficiency on the growth of maize.

Phosphate solubilizing bacteria (PSB) has ability to convert insoluble form of phosphorous to an available form. Applications of PSB as inoculants increase the phosphorus uptake by plant in the agriculture field. In this study, isolation and identification of PSB were carried out in Indian agriculture field (Nainital region, Uttarakhand). A total of 8 phosphate solubilizing bacterial colonies were isolated on the Pikovskaya’s (PKV) agar medium, containing insoluble tricalcium phosphate (TCP). The colonies showed clear halo zones around the bacterial growth were considered as phosphate solubilizers. Out of 8 bacterial isolates, 3 isolates showed high phosphate solubilization index (PSI) ranged from 4.88 ± 0.69 to 4.48 ± 0.30, lower pH ranging 3.08 ± 0.08 to 3.82 ± 0.12 and high phosphate solubilization varied from 305.49 ± 10 μg/ml to 277.72 ± 1.45 μg/ml, were selected for further characterization. Based on the 16 S rRNA gene sequence analysis A4 isolate and H6 isolate were closely related to Alcaligenes aquatilis (99%), and C1 isolate was closely related to Burkholderia cepacia (99%). In addition, pot examination also showed the greatest efficiency in promotion of maize growth compared to uninoculated plant. Isolated PSB were able to produce different organic acids (such as gluconic acids, formic acid, and citric acid) in the culture supernatant and may consider as the principle mechanism for phosphate solubilization. This study clearly indicates that A4, C1 and H6 isolates may use as a biofertilizers in ecological agricultural systems instead of synthetic chemicals and may help to sustain environmental health and soil productivity.

Complete Genome Sequence of Burkholderia cenocepacia CR318, a Phosphate-Solubilizing Bacterium Isolated from Corn Root.

ABSTRACTHere, we report the complete genome sequence of the phosphate-solubilizing bacterium Burkholderia cenocepacia CR318, consisting of three circular chromosomes of 3,511,146 bp, 3,097,552 bp, and 1,056,069 bp. The data presented will facilitate further insight into the mechanisms of phosphate solubilization and its application for agricultural and ecological sustainability.

Spectroscopic characterization of dissolved organic matter from sludge solubilization treatment by micro-bubble technology

In this study, the micro-bubble were used for the sludge solubilization process. In order to investigate the enhancement of sludge solubilization by micro-bubbles, the performance of the micro-bubble system and a conventional bubble system (the control one) was compared in terms of sludge solubilization. The performance in the micro-bubble reactor was much better than the control one, as a result total suspended solid (TSS) was rapidly decreased to 2325.19TSSL−1. To investigate the mechanism of the sludge solubilization, the constituents of dissolved organic matter (DOM) from the sludge solubilization was investigated using fluorescence spectroscopy. Compared to the DOM from the reactor using conventional bubbles, the DOM from the micro-bubbles reactor contained higher protein- and humic-like substances. Moreover, the total integrated fluorescence intensity (TOT) were constantly decreased by 18.37% in the control one and increased by 34.39% in the micro-bubble reactor. The results mean that the sludge were effectively solubilized, and organic molecules were released. Polymerase chain reactions-denaturing gradient gel electrophoresis (PCR-DGGE) was used to analyse the microbial communities after a micro-bubble process. The dominant bacteria in the micro-bubble reactor were identified as Delftia sp., Sphenophorus levis and Stenotrophomonas sp., which were benefit to the cleavage of refractory organics. Scanning Electron Microscopy (SEM) inspection showed that the sludge after the micro-bubble process presented more pores and channels on the sludge surface; the micro-bubbles was good at forming zoogloea, which was helpful for oxygen and mass transfer. Overall, the results indicate that the micro-bubbles aeration could improve the solubilization of sludge.

Microbial Phosphorus Solubilization and Its Potential for Use in Sustainable Agriculture.

The use of excess conventional Phosphorus (P) fertilizers to improve agricultural productivity, in order to meet constantly increasing global food demand, potentially causes surface and ground water pollution, waterway eutrophication, soil fertility depletion, and accumulation of toxic elements such as high concentration of selenium (Se), arsenic (As) in the soil. Quite a number of soil microorganisms are capable of solubilizing/mineralizing insoluble soil phosphate to release soluble P and making it available to plants. These microorganisms improve the growth and yield of a wide variety of crops. Thus, inoculating seeds/crops/soil with Phosphate Solubilizing Microorganisms (PSM) is a promising strategy to improve world food production without causing any environmental hazard. Despite their great significance in soil fertility improvement, phosphorus-solubilizing microorganisms have yet to replace conventional chemical fertilizers in commercial agriculture. A better understanding of recent developments in PSM functional diversity, colonizing ability, mode of actions and judicious application should facilitate their use as reliable components of sustainable agricultural systems. In this review, we discussed various soil microorganisms that have the ability to solubilize phosphorus and hence have the potential to be used as bio fertilizers. The mechanisms of inorganic phosphate solubilization by PSM and the mechanisms of organic phosphorus mineralization are highlighted together with some factors that determine the success of this technology. Finally we provide some indications that the use of PSM will promote sustainable agriculture and conclude that this technology is ready for commercial exploitation in various regions worldwide.

Effect of acid phosphatase produced by Trichoderma asperellum Q1 on growth of Arabidopsis under salt stress

Salt stress is a major environmental factor that inhibits crop growth. Trichoderma spp. are the most efficient biocontrol fungi and some of the strains can stimulate plant growth. Phosphate solubilization is known as one of the main mechanisms in promoting plant growth, but the underlying mechanisms of phosphate solubilization in the salinity still need to be explored. The Trichoderma asperellum Q1 isolated and identified in our lab is a beneficial rhizosphere biocontrol fungus with a high phosphate solubilization activity. It could produce acid and alkaline phosphatases when using insoluble organic phosphorus as the sole phosphorus source, the salt stress increased the phosphorus-solubilization ability of the strain and the activities of the two enzymes. Furthermore, an acid phosphatase was purified from the fermentation broth by ammonium sulphate precipitation, ion-exchange, and gel filtration chromatography. Its molecular weight was 55 kDa as determined by SDS-PAGE. The purified acid phosphatase was used to investigate growth performance of Arabidopsis thaliana by plate assay and the result showed that it contributed to Arabidopsis growth by transforming organic phosphate into a soluble inorganic form under salt stress. To our knowledge, this is the first report on acid phosphatase purification from T. asperellum and its function in regulation of plant growth under salt stress.

Impact of Micellar Surfactant on Supersaturation and Insight into Solubilization Mechanisms in Supersaturated Solutions of Atazanavir.

The goals of this study were to determine: 1) the impact of surfactants on the "amorphous solubility"; 2) the thermodynamic supersaturation in the presence of surfactant micelles; 3) the mechanism of solute solubilization by surfactant micelles in supersaturated solutions. The crystalline and amorphous solubility of atazanavir was determined in the presence of varying concentrations of micellar sodium dodecyl sulfate (SDS). Flux measurements, using a side-by-side diffusion cell, were employed to determine the free and micellar-bound drug concentrations. The solubilization mechanism as a function of atazanavir concentration was probed using fluorescence spectroscopy. Pulsed gradient spin-echo proton nuclear magnetic resonance (PGSE-NMR) spectroscopy was used to determine the change in micelle size with a change in drug concentration. Changes in the micelle/water partition coefficient, K m/w , as a function of atazanavir concentration led to erroneous estimates of the supersaturation when using concentration ratios. In contrast, determining the free drug concentration using flux measurements enabled improved determination of the thermodynamic supersaturation in the presence of micelles. Fluorescence spectroscopic studies suggested that K m/w changed based on the location of atazanavir solubilization which in turn changed with concentration. Thus, at a concentration equivalent to the crystalline solubility, atazanavir is solubilized by adsorption at the micelle corona, whereas in highly supersaturated solutions it is also solubilized in the micellar core. This difference in solubilization mechanism can lead to a breakdown in the prediction of amorphous solubility in the presence of SDS as well as challenges with determining supersaturation. PGSE-NMR suggested that the size of the SDS micelle is not impacted at the crystalline solubility of the drug but increases when the drug concentration reaches the amorphous solubility, in agreement with the proposed changes in solubilization mechanism. Micellar solubilization of atazanavir is complex, with the solubilization mechanism changing with differences in the degree of (super)saturation. This can result in erroneous predictions of the amorphous solubility and thermodynamic supersaturation in the presence of solubilizing additives. This in turn hinders understanding of the driving force for phase transformations and membrane transport, which is essential to better understand supersaturating dosage forms.

Biomembrane solubilization mechanism by Triton X-100: a computational study of the three stage model.

The solubilization mechanism of lipid membranes in the presence of Triton X-100 (TX-100) is investigated at molecular resolution using molecular dynamics (MD) simulations. Thanks to the large time and length scales accessible by the hybrid particle-field formulation of the models employed here, the complex process of membrane solubilization has been studied, with the goal of verifying the three stage model reported in the literature. DPPC lipid bilayers and vesicles have been studied at different concentrations of the TX-100 detergent employing coarse grained (CG) models. Systems up to ∼600.000 beads, corresponding to more than 2 millions heavy atoms, have been simulated. Moreover, in order to clarify several experimental pieces of evidence, both slow and fast detergent partition scenarios have been investigated. Flat and curved (vesicles) lipid bilayer surfaces, interacting with TX-100, have been considered to study the curvature effects on the detergent partition rate in the membrane. Shape and conformational changes of mixed DPPC/TX-100 vesicles, as a function of TX-100 content, have also been studied. In particular, high curvature surfaces, corresponding to a higher local TX-100 content, promote a membrane rupture. In flat lipid surfaces, on the time scale simulated the detergent partition is almost absent, following a different pathway of the solubilization membrane mechanism.