Static Light Scattering Data Research Articles

Predicting Experimental B22 Values and the Effects of Histidine Charge States for Monoclonal Antibodies Using Coarse-Grained Molecular Simulations.

Static light scattering (SLS) was used to characterize five monoclonal antibodies (MAbs) as a function of total ionic strength (TIS) at pH values between 5.5 and 7.0. Second osmotic virial coefficient (B22) values were determined experimentally for each MAb as a function of TIS using low protein concentration SLS data. Coarse-grained molecular simulations were performed to predict the B22 values for each MAb at a given pH and TIS. To include the effect of charge fluctuations of titratable residues in the B22 calculations, a statistical approach was introduced in the Monte Carlo algorithm based on the protonation probability based on a given pH value and the Henderson-Hasselbalch equation. The charged residues were allowed to fluctuate individually, based on the sampled microstates and the influence of electrostatic interactions on net protein-protein interactions during the simulations. Compared to static charge simulations, the new approach provided improved results compared to experimental B22 values at pH conditions near the pKa of titratable residues.

Ultra-/Small Angle X-ray Scattering (USAXS/SAXS) and Static Light Scattering (SLS) Modeling as a Tool to Determine Structural Changes and Effect on Growth in S. epidermidis.

Usually, to characterize bacterial cells' susceptibility to antimicrobials, basic microbiology techniques such as serial dilutions or disk assays are used. In this work, we present an approach focused on combining static light scattering (SLS) and ultra-/small angle X-ray scattering (USAXS/SAXS). This approach was used to support microbiology techniques, with the aim of understanding the structural changes caused to bacteria when they are exposed to different stresses like pH, oxidation, and surfactants. Using USAXS/SAXS and SLS data, we developed a detailed multiscale model for a Gram-positive bacterium, S. epidermidis, and we extracted information regarding changes in the overall size and cell thickness induced by different stresses (i.e., pH and hydrogen peroxide). Increasing the concentration of hydrogen peroxide leads to a progressive reduction in cell wall thickness. Moreover, the concomitant use of pH and hydrogen peroxide provides evidence for a synergy in inhibiting the S. epidermidis growth. These promising results will be used as a starting base to further investigate more complex formulations and improve/refine the data modeling of bacteria in the small angle scattering regime.

Protein-Protein Interactions of Highly Concentrated Monoclonal Antibody Solutions via Static Light Scattering and Influence on the Viscosity.

The ability to design and formulate mAbs to minimize attractive interactions at high concentrations is important for protein processing, stability, and administration, particularly in subcutaneous delivery, where high viscosities are often challenging. The strength of protein-protein interactions (PPIs) of an IgG1 and IgG4 monoclonal antibody (mAb) from low to high concentration was determined by static light scattering (SLS) and used to understand viscosity data. The PPI were tuned using NaCl and five organic ionic co-solutes. The PPI strength was quantified by the normalized structure factor S(0)/ S(0)HS and Kirkwood-Buff integral G22/ G22,HS (HS = hard sphere) determined from the SLS data and also by fits with (1) a spherical Yukawa potential and (2) an interacting hard sphere (IHS) model, which describes attraction in terms of hypothetical oligomers. The IHS model was better able to capture the scattering behavior of the more strongly interacting systems (mAb and/or co-solute) than the spherical Yukawa potential. For each descriptor of PPI, linear correlations were obtained between the viscosity at high concentration (200 mg/mL) and the interaction strengths evaluated both at low (20 mg/mL) and high concentrations (200 mg/mL) for a given mAb. However, the only parameter that provided a correlation across both mAbs was the oligomer mass ratio ( moligomer/ mmonomer+dimer) from the IHS model, indicating the importance of self-association (in addition to the direct influence of the attractive PPI) on the viscosity.

Light-scattering data of protein and polymer solutions: A new approach for model validation and parameter estimation

The development of separation processes for polymers or proteins from aqueous solutions requires a high amount of experimental effort, including phase-equilibrium data such as solid-liquid, liquid-liquid or vapor-liquid equilibria. This effort can be reduced by means of thermodynamic models. This work presents a new method for parameter estimation and validation of thermodynamic models by means of static-light-scattering (SLS) measurements. In this work the Perturbed-Chain Statistical Associating Fluid Theory (PC-SAFT) was used to predict directly the SLS data (Rayleigh ratio) of macromolecular solutions. In a first step, SLS data were measured for binary water/polyethylene glycol (PEG molecular weight ranging from 2000 to 12000 g/mol) mixtures and for binary water/lysozyme mixtures. Applying pure-component PC-SAFT parameters from literature, the SLS data of these binary mixtures were successfully predicted with PC-SAFT. In a second step, one binary interaction parameter between lysozyme and PEG was adjusted to new experimental SLS data of buffered PEG/lysozyme/water solutions with PEG6000 concentration of 20 g/L. Finally, SLS data for buffered ternary PEG/lysozyme/water solutions with PEG of different molecular weights (2000–12000 g/mol) and different concentrations (1–50 g/L) were accurately predicted with PC-SAFT. Thus, (1) the proposed approach allows predicting SLS data, and (2) the method provides an access to the estimation of model parameters by means of experimental SLS data, which are accessible with much less effort than experimental phase-equilibrium data.

The Use of Size Exclusion Chromatography to Monitor Protein Self-Assembly

High resolution size exclusion chromatography (SEC) coupled with static light scattering (SLS) analyses were conducted to study the effect of the mobile phase ionic strength and protein concentration on the output of SEC experiments. The results highlight the effect of small changes in the mobile phase composition on the estimation of molar masses estimated from retention time-based calibration curve compared with those obtained from SLS analysis. By comparing the SLS data with the SEC chromatograms, we show that SEC can provide helpful information on the protein aggregation state as macromolecules approach known precipitation points in their phase diagrams. This suggests the potential use of SEC as an easily accessible lab-based scanning methodology to monitor protein self-assembly prior to nucleation and crystallization. Implications for the use of SEC to study protein phase diagrams are discussed.

Mesoscopic Structural Aspects of Ca2+-Triggered Polymer Chain Folding of a Tetraphenylethene-Appended Poly(acrylic acid) in Relation to Its Aggregation-Induced Emission Behavior

We recently reported that tetraphenylethene-appended poly(acrylic acid) derivatives [PAA-TPEx (x = 0.01–0.05)] provide a fluorescent Ca2+ sensor, where aggregation-induced emission (AIE) of the TPE pendants occurs in conjunction with Ca2+-triggered polymer-chain folding. On the basis of dynamic and static light-scattering data, here we discuss the hydrodynamic radius and molar mass of PAA-TPE0.01 in the presence of Ca2+, Mg2+, or Na+ at various concentrations and elucidate the origin of the Ca2+ selectivity. In contrast to Na+, which exclusively triggered nonfluorescent interpolymer aggregation of PAA-TPE0.01, Ca2+ and Mg2+ induced polymer-chain folding associated with AIE from the TPE pendants. Importantly, Ca2+ caused polymer-chain folding more effectively than Mg2+. Consequently, polymer aggregates formed in the presence of Ca2+ possessed a much higher inner density than those formed in the presence of Mg2+, leading to a more pronounced AIE behavior and, in turn, the Ca2+ ion selectivity over Mg2+.

Colloidal Aggregates of Pd Nanoparticles Supported by Larch Arabinogalactan

Palladium nanoparticles (PdNPs) are used in catalysis, hydrogen storage, biomedicine, and so on. Arranging the self-assembly of PdNPs within colloidal aggregates is desirable for improving their consumer properties. Stable widely dispersed colloidal aggregates of larch arabinogalactan (LARB) containing nanosized (5-nm) PdNPs were obtained by reducing Pd ions in alkaline solutions of LARB. Centrifugation resulted in a set of LARB-PdNP colloids ranging from 60 to 240 nm. The colloids were studied by static light scattering (SLS) and dynamic light scattering (DLS). The SLS data presented as Kratki plots correspond to a particle scattering factor of linear rather than branched chains. The fractal dimension of the LARB-PdNP colloids was found by SLS to be d = 1.96, which is between the values for diffusion- and reaction-limited aggregation. This result is ascribed to the aggregate's internal motion, which is evident from the power-law exponent of the dependence of the DLS relaxation rate on the scattering vector, <Γ> ~ q(α) with α = 2.24. The structure-sensitive ratio of the radius of gyration to the hydrodynamic radius was found to vary within the interval of 0.8 ≤ R(g)/R(h) ≤ 1.2 corresponding, to the spherical form of LARB-PdNP colloids. A spiderweblike PdNP distribution pattern was observed by transmission electron microscopy. Insertion of PdNPs did not affect the fractal dimension, the power-law exponent α, or the architecture of the pristine LARB aggregates in water. The red shift of the surface plasmon extinction observed with increasing LARB-PdNP colloidal size indicates the collective optical response of the PdNP ensemble in the colloid.

Structure of PEP–PEO block copolymer micelles: exploiting the complementarity of small-angle X-ray scattering and static light scattering

The structure of large block copolymer micelles is traditionally determined by small-angle neutron scattering (SANS), covering a large range of scattering vectors and employing contrast variation to determine the overall micelle morphology as well as the internal structure on shorter length scales. The present work shows that the same information can be obtained by combining static light scattering (SLS) and small-angle X-ray scattering (SAXS), which provide information on, respectively, large and short length scales. Micelles of a series of block copolymers of poly(ethylene propylene)-b-poly(ethylene oxide) (PEP–PEO) in a 70% ethanol solution are investigated. The polymers have identical PEP blocks of 5.0 kDa and varying PEO blocks of 2.8–49 kDa. The SLS contrasts of PEP and PEO are similar, providing a homogeneous contrast, making SLS ideal for determining the overall micelle morphology. The SAXS contrasts of the two components are very different, allowing for resolution of the internal micelle structure. A core–shell model with a PEP core and PEO corona is fitted simultaneously to the SAXS and SLS data using the different contrasts of the two blocks for each technique. With increasing PEO molecular weight, a transition from cylindrical to spherical micelles is observed. This transition cannot be identified from the SAXS data alone, but only from the SLS data.

Polymorph‐ and Size‐Dependent Uptake and Toxicity of TiO2 Nanoparticles in Living Lung Epithelial Cells

The cellular uptake and distribution of five types of well-characterized anatase and rutile TiO(2) nanoparticles (NPs) in A549 lung epithelial cells is reported. Static light scattering (SLS), in-vitro Raman microspectroscopy (μ-Raman) and transmission electron spectroscopy (TEM) reveal an intimate correlation between the intrinsic physicochemical properties of the NPs, particle agglomeration, and cellular NP uptake. It is shown that μ-Raman facilitates chemical-, polymorph-, and size-specific discrimination of endosomal-particle cell uptake and the retention of particles in the vicinity of organelles, including the cell nucleus, which quantitatively correlates with TEM and SLS data. Depth-profiling μ-Raman coupled with hyperspectral data analysis confirms the location of the NPs in the cells and shows that the NPs induce modifications of the biological matrix. NP uptake is found to be kinetically activated and strongly dependent on the hard agglomeration size-not the primary particle size-which quantitatively agrees with the measured intracellular oxidative stress. Pro-inflammatory responses are also found to be sensitive to primary particle size.

Static Light Scattering of Concentrated Particle Systems in the Rayleigh-Debye-Gans Regime: Modeling and Data Analysis

In this work we give an overview of the Rayleigh-Debye-Gans (RDG) theory applied to the analysis of static light scattering (SLS) data of different types of concentrated particle systems. First some useful models needed to analyze SLS data under the RDG regime for concentrated particle systems are presented. We consider monodisperse as well as polydisperse systems of spherical particles. Then we present some techniques for analyzing the SLS data in different contexts with the aim of gathering information about: particle size and shape, particle size distribution, particle concentration, and some other useful parameters characterizing the particle systems. Finally, we report an application of some of the models and methods illustrated previously. They were used to characterize a system of concentrated polymer particles embedded in a polymer matrix, formed as the result of a phase separation induced by polymerization in a polymer blend.

Structure and Gelation Mechanism of Tunable Guanosine-Based Supramolecular Hydrogels

The mechanism of gelation of 50/50 w/w mixtures of guanosine (G) and 2',3',5'-tri-O-acetylguanosine (TAcG) in aqueous 0.354 M KCl was investigated using a combination of static light scattering (SLS), polarized and depolarized dynamic light scattering (VV and VH DLS), small-angle neutron and X-ray scattering (SANS and SAXS), and viscometric experiments. SLS and viscometry show a dramatic increase in apparent molecular weight and hydrodynamic volume at 0.2 wt % and 0.3 wt %, respectively, indicating the critical concentration for self-association of G/TAcG quartets into columnar assemblies lies below 0.2 wt %. Above this concentration, SANS and SAXS generate complementary information on the structure of the individual columnar stacks. VV and VH DLS results indicate bimodal correlation functions, whose properties suggest, respectively, translational and rotational diffusion of a bimodal distribution of particles. The fast mode appears to originate from fibrillar agglomerates of G/TAcG columnar quartet assemblies, while the slow mode comes from microgel domains. Guinier plot analysis of the SLS data probes the internal structure of the microgel domains. Collectively, the results suggest that sol and microgel phases coexist below the macroscopic gel point, and that the sol phase contains individual columnar stacks of G/TAcG quartets and fibrillar aggregates formed via lateral aggregation of these columnar assemblies. With increasing concentration, the DLS data indicate a progressive increase in the volume fraction of microgel domains, which ultimately leads to macroscopic gelation. Prior observation of a transient network contribution to the gel rheology at low temperature is attributed to the presence of individual columnar stacks within the gel network.

Evaluation of light scattering models to characterize concentrated polymer particles embedded in a solid polymer matrix

This work deals with the application of the static light scattering (SLS) model of Vrij (VM) for the characterization of a spherical polydisperse concentrated polymer particle system. This model is the exact solution for the SLS of such mixture of particles in the Percus–Yevick approximation. The analyzed polymer particle samples are obtained by solution polymerization of isobornyl methacrylate in polyisobutylene. At the end of the polymerization, as a result of phase separation, a particle system of micrometer sized particles with a moderate distribution of sizes and a volume fraction between 5 and 10% is formed. The SLS data were also analyzed using the local monodisperse approximation (LMA), a well-known approximation to the model of Vrij. As expected, the estimations with the VM gave better results than those performed with the LMA model for the parameters related to the shape of the particle size distribution as compared with independent determinations of these quantities obtained from scanning electron microscopy micrographs. However, the main motivation to use the more rigorous model seems to be the fact that the volume fraction of particles can be extracted from the data even when relative SLS measurements are used. © 2010 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 48: 958–963, 2010

New insights regarding the cyclodextrin/AAS self-assembly: A molar ratio dependent system

The assembly between acetylsalicylic acid (AAS) and β-cyclodextrin (βCD), was characterized using NMR spectroscopy ( 1H, T 1, and NOESY), Isothermal Titration Calorimetry (ITC) and Static Light Scattering (SLS). NMR data showed the preferential orientation inside the cyclodextrin cavity, yet suggests the formation of high ordered complexes. Calorimetric titration showed a gradually less exothermic signal in an overall range of analyzed βCD concentrations, suggesting simultaneous aggregation and dessolvation of inclusion compounds. SLS data confirmed the self assembly hypothesis above 10 − 4 mM, bringing new insights regarding aggregation in cyclodextrin system, which could act as modulator of supramolecular structure of complex and consequently influence its use as control release system.

Solution properties of polyaniline

AbstractSolution properties of polyaniline (PANI) synthesized at various temperatures were studied using static light scattering (SLS), intrinsic viscosity, and dynamic light scattering (DLS). We demonstrated that average radius of gyration 〈Rg〉, intrinsic viscosity [η], and average hydrodynamic radius 〈RH〉, of polyaniline molecules in dilute N‐methyl‐2‐pyrrolidinone (NMP) solutions increased with decreasing synthesis temperatures, i.e.; increasing molecular weight. SLS data demonstrate that second virial coefficient (A2) decreased with increasing particle sizes suggesting that solubility of PANI in NMP decreased with increasing particle sizes. We also find that the polymers extend as the polymer concentration is lowered and that the increase in the hydrodynamic radius can be expressed by a power law of the electrostatic screening length. This behavior is typical of polyelectrolytes in dilute solution, providing a basis for understanding the conformation changes of this metallic polymer in solution. Copyright © 2009 Society of Chemical Industry

Synthesis, micelle formation, and bulk properties of poly(ethylene glycol)‐b‐poly(pentafluorostyrene)‐g‐polyhedral oligomeric silsesquioxane amphiphilic hybrid copolymers

AbstractThe synthesis, micelle formation, and bulk properties of semifluorinated amphiphilic poly(ethylene glycol)‐b‐poly(pentafluorostyrene)‐g‐cubic polyhedral oligomeric silsesquioxane (PEG‐b‐PPFS‐g‐POSS) hybrid copolymers is reported. The synthesis of amphiphilic PEG‐b‐PPFS block copolymers are achieved using atom transfer radical polymerization (ATRP) at 100 °C in trifluorotoluene using modified poly(ethylene glycol) as a macroinitiator. Subsequently, a proportion of the reactive para‐F functionality on the pentafluorostyrene units was replaced with aminopropylisobutyl POSS through aromatic nucleophilic substitution reactions. The products were fully characterized by 1H‐NMR and GPC. The products, PEG‐b‐PPFS and PEG‐b‐PPFS‐g‐POSS, were subsequently self‐assembled in aqueous solutions to form micellar structures. The critical micelle concentrations (cmc) were estimated using two different techniques: fluorescence spectroscopy and dynamic light scattering (DLS). The cmc was found to decrease concomitantly with the number of POSS particles grafted per copolymer chain. The hydrodynamic particle sizes (Rh) of the micelles, calculated from DLS data, increase as the number of POSS molecules grafted per copolymer chain increases. For example, Rh increased from ∼60 nm for PEG‐b‐PPFS to ∼80 nm for PEG‐b‐PPFS‐g‐POSS25 (25 is the average number of POSS particles grafted copolymer chain). Static light scattering (SLS) data confirm that the formation of larger micelles by higher POSS containing copolymers results from higher aggregation numbers (Nagg), caused by increased hydrophobicity. The Rg/Rh values, where Rg is the radius of gyration calculated from SLS data, are consistent with a spherical particle model having a core‐shell structure. Thermal characterization by differential scanning calorimetry (DSC) reveals that the grafted POSS acts as a plasticizer; the glass transition temperature (Tg) of the PPFS block in the copolymer decreases significantly with increasing POSS content. Finally, the rhombohedral crystal structure of POSS in PEG‐b‐PPFS‐g‐POSS was verified by wide angle X‐ray diffraction measurements. © 2009 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 48: 152–163, 2010

Unusual behavior in light scattering experiments of poly(N-vinylimidazole) prepared by precipitation polymerization

Poly(N-vinylimidazole) (PVI) was synthesized by the precipitation polymerization using 2,2’-azobis(isobutyronitrile) (AIBN; initiator) and benzene (solvent) at two different monomer/initiator ratios. The solution polymerization was also performed with the following initiator/solvent systems: AIBN/water–methanol mixture (1:1 by volume) and 4,4’-azobis(4-cyanovaleric acid)/aqueous HCl solution (pH 0.8). All the four preparations of PVI in ethanol and in 0.2 M NaCl (pH 3 with HCl) were examined by dynamic light scattering (DLS). The CONTIN analysis of DLS data for each preparation from the solution polymerization showed a unimodal distribution in both ethanol and aqueous solvents. A good agreement was obtained between the molar masses in these different solvents by static light scattering (SLS). However, the polymers from the precipitation polymerization exhibited a heterogeneous bimodal distribution in DLS under the same conditions as above, indicating that the SLS data as in reference [6] (Savin et al. Macromolecules 37:6565) cause a serious error in the understanding of solution behavior of PVI.

Interaction of cylindrical polymer brushes in dilute and semi-dilute solution

We present a systematic study of flexible cylindrical brush-shaped macromolecules in a good solvent by small-angle neutron scattering (SANS), static light scattering (SLS), and by dynamic light scattering (DLS) in dilute and semi-dilute solution. The SLS and SANS data extrapolated to infinite dilution lead to the shape of the polymer that can be modeled in terms of a worm-like chain with a contour length of 380 nm and a persistence length of 17.5 nm. SANS data taken at higher polymer concentration were evaluated by using the polymer reference interaction site model (PRISM). We find that the persistence length reduce from 17.5 nm at infinite dilution to 5.3 nm at the highest concentration (volume fraction 0.038). This is comparable with the decrease of the persistence length in semi-dilute concentration predicted theoretically for polyelectrolytes. This finding reveals a softening of stiffness of the polymer brushes caused by their mutual interaction.

Softening of the stiffness of bottle-brush polymers by mutual interaction

We study bottle-brush macromolecules in a good solvent by small-angle neutron scattering (SANS), static light scattering (SLS), and dynamic light scattering (DLS). These polymers consist of a linear backbone to which long side chains are chemically grafted. The backbone contains about 1600 monomer units (weight average) and every second monomer unit carries side chains with approximately 60 monomer units. The SLS and SANS data extrapolated to infinite dilution lead to the form factor of the polymer that can be described in terms of a wormlike chain with a contour length of 380 nm and a persistence length of 17.5 nm. An analysis of the DLS data confirms these model parameters. The scattering intensities taken at finite concentration can be modeled using the polymer reference interaction site model. It reveals a softening of the bottle-brush polymers caused by their mutual interaction. We demonstrate that the persistence decreases from 17.5 nm down to 5 nm upon increasing the concentration from dilute solution to the highest concentration (40.59 gl) under consideration. The observed softening of the chains is comparable to the theoretically predicted decrease of the electrostatic persistence length of linear polyelectrolyte chains at finite concentrations.

Static light scattering study of complex formation between protein and neutral water-soluble polymer

Complex formation of poly( N-isopropylacrylamide) (PNIPA) having a weight-average molecular weight of 1,720,000 g/mol with human serum albumin (HSA), ovalbumin (OVA) and lysozyme (LYZ) was studied in an aqueous medium containing 0.01 M NaCl and adjusted to pH 3. The polymer–protein mixtures at different molar ratios ( r m) were examined by static light scattering (SLS). The analysis of SLS data using our own approach [Kokufuta et al., Langmuir 15 (1999) 940; Biomacromolecules 4 (2003) 728] showed that the molecular weight of each resulting complex is smaller than that of the interpolymer complex composed of two polymer chains plus one protein. This indicates the formation of an intrapolymer complex in all the polymer–protein systems studied. Thus, at each r m we calculated the number of bound proteins per polymer, the value of which was OVA > HSA > LYZ in order. These results were compared with the hydropathy profiles of each protein which are a good tool for obtaining an information about distribution of hydrophobic and hydrophilic segments in a protein. It has become apparent that the hydrophobic interaction between polymer and protein plays an important role in the intrapolymer complex formation.

Synthesis of Well-Defined Amphiphilic Block Copolymers Having Phospholipid Polymer Sequences as a Novel Biocompatible Polymer Micelle Reagent

To realize safer and effective drug administration, novel well-defined and biocompatible amphiphilic block copolymers containing phospholipid polymer sequences were synthesized. At first, the homopolymer of 2-methacryloyloxyethylphosphorylcholine (MPC) was synthesized in water by reversible addition-fragmentation chain transfer (RAFT) controlled radical polymerization. The "living" polymerization was confirmed by the fact that the number-average molecular weight increased linearly with monomer conversion while the molecular weight distribution remained narrow independent of the conversion. The poly(MPC) thus prepared is end-capped with a dithioester moiety. Using the dithioester-capped poly(MPC) as a macro chain transfer agent, AB diblock copolymers of MPC and n-butyl methacrylate (BMA) were synthesized. Associative properties of the amphiphilic block copolymer (pMPC(m)-BMA(n)) with varying poly(BMA) block lengths were investigated using NMR, fluorescence probe, static light scattering (SLS), and quasi-elastic light scattering (QELS) techniques. Proton NMR data in D2O indicated highly restricted motions of the n-butyl moieties, arising from hydrophobic associations of poly(BMA) blocks. Fluorescence spectra of N-phenyl-1-naphthylamine indicated that the probes were solubilized in the polymer micelles in water. The formation of polymer micelles comprising a core with poly(BMA) blocks and shell with hydrophilic poly(MPC) blocks was suggested by SLS and QELS data. The size and mass of the micelle increased with increasing poly(BMA) block length. With an expectation of a pharmaceutical application of pMPC(m)-BMA(n), solubilization of a poorly water-soluble anticancer agent, paclitaxel (PTX), was investigated. PTX dissolved well in aqueous solutions of pMPC(m)-BMA(n) as compared with pure water, implying that PTX is incorporated into the hydrophobic core of the polymer micelle. Since excellent biocompatible poly(MPC) sequences form an outer shell of the micelle, pMPC(m)-BMA(n) may find application as a promising reagent to make a good formulation with a hydrophobic drug.