Physicochemical characterization of phospholipid solubilized mixed micelles and a hydrodynamic model of interfacial fluorescence quenching

Mixed micelles of solubilized dimyristoyl phosphatidylcholine (DMPC) and the zwitterionic detergent dodecyldimethylammoniopropane sulfonate are characterized employing time-resolved fluorescence quenching (TRFQ), electron spin resonance (ESR), and surface tensiometry toward the goal of investigating interfacial reactions using these micelles as host reaction media. The properties measured are the micelle aggregation numbers, interfacial hydration index, microviscosity, and the critical micelle concentrations for various molar fractions, XDMPC, of DMPC, 0相似文献   

Small-angle neutron scattering of ionic perfluoropolyether micellar solutions: role of counterions and temperature

This paper reports a small-angle neutron scattering (SANS) characterization of perfluoropolyether (PFPE) aqueous micellar solutions with lithium, sodium, cesium and diethanol ammonium salts obtained from a chlorine terminated carboxylic acid and with two perfluoroisopropoxy units in the tail (n(2)). The counterion and temperature effects on the micelle formation and micellar growth extend our previous work on ammonium and potassium salts n(2) micellar solutions. Lithium, sodium, cesium and diethanol ammonium salts are studied at 0.1 and 0.2 M surfactant concentration in the temperature interval 28-67 degrees C. SANS spectra have been analyzed by a two-shell model for the micellar form factor and a screened Coulombic plus steric repulsion potential for the structure factor in the frame of the mean spherical approximation of a multicomponent system reduced to a generalized one component macroions system (GOCM). At 28 degrees C, for all the salts, the micelles are ellipsoidal with an axial ratio that increases from 1.6 to 4.2 as the counterion volume increases. The micellar core short axis is 13 A and the shell thickness 4.0 A for the alkali micelles, and 14 and 5.1 A for the diethanol ammonium micelles. Therefore, the core short axis mainly depends on the surfactant tail length and the shell thickness on the carboxylate polar head. The bulky diethanol ammonium counterion solely influences the shell thickness. Micellar charge and average aggregation number depend on concentration, temperature and counterion. At 28 degrees C, the fractional ionization decreases vs the counterion volume (or molecular weight) increase at constant concentration for both C = 0.1 M and C = 0.2 M. The increase of the counterion volume leads also to more ellipsoidal shapes. At C = 0.2 M, at 67 degrees C, for sodium and cesium micelles the axial ratio changes significantly, leading to spherical micelles with a core radius of 15 A, lower average aggregation number, and larger fractional ionization.     

Effect of Increasing Concentration of Each of Three Polar Solvents (1,4-Dioxane, Dimethyl Sulfoxide, N,N-Dimethylformamide) on Changes in the Shape of Polysorbate 20 Micelles

The effect of increasing concentration of each of three polar solvents [0–40 % (v/v) 1,4-dioxane, 0–40 % (v/v) dimethyl sulfoxide (DMSO), and 0–60 % (v/v) N,N-dimethylformamide (DMF)] on changes in the shape of the surfactant polysorbate 20 (Tween 20) micelles in the aqueous, polar solvent, sodium phosphate buffer solutions (pH = 7.2, ionic strength 2.44 mmol·L^?1) were investigated by using small-angle X-ray scattering. The effect of increasing concentration of 1,4-dioxane is that the micelle shape changed from core–shell cylindrical micelles to core–shell disc micelles between concentrations of 10 and 20 % (v/v) 1,4-dioxane, and then from core–shell disc micelles to core–shell elliptic disc micelles between concentrations of 30 and 40 % (v/v) 1,4-dioxane. The effect of increasing concentration of DMSO is that the micelles changed from core–shell cylindrical micelles to core–shell disc micelles between concentrations of 0 and 10 % (v/v) DMSO. The effect of increasing concentration of DMF is that it changed the core–shell cylindrical micelles to core–shell disc micelles between concentrations of 30 and 40 % (v/v) DMF. The common effect is that the solvents shortened the height of the micelle, that is, they squashed the micelle. Moreover, the specific effect of 1,4-dioxane is that this solvent squashed and squeezed the micelle.     

The structure and properties of medium-chain surfactant solutions: a case study of sodium octanoate

In the paper the most characteristic properties of binary sodium octanoate solutions of variable ion strengths are discussed. Both pre- and postmicellar association is investigated with reference to available scattering, spectroscopic and thermodynamic data. The focus is then placed on references dealing with, or referring to, results including sodium octanoate. A picture is offered illustrating the sodium octanoate micelle as a rather unstable entity including micelle sizes from oligomeric pre-associates up to some 20 monomers. Due to this circumstance the molecular features obtained with different scattering and spectroscopic techniques are rather divergent. However, the structure emerging describes the micelle as consisting of a small “dry” hydro-carbon core with a radius shorter than the fully extended heptyle chain of the octanoate. Instead a “rough shell” encompassing the hydrated polar head groups, some “wet” methylene/methyle groups and the hydrated counterions separates the micelle from the surrounding solvent. On purely geometric grounds this hydrated shell represent, however, more than 50% of the micellar volume. The numerous distinct properties of medium-chain surfactants should thence not, as is frequently done, be related to those of long-chain surfactants! At high concentrations of octanoate or salt, or upon solubilization, the average degree of water contact seem to diminish due to an increased aggregation number or a lack of available “free” hydration water. The latter effect is suggested to produce observable effects at the second critical concentration as well as close to the phase boundary. The influence of solubilizates are dealth with only when the results provide significant information on the properties of the binary system.     

Effect of N-glycinylmaleamic acid on microstructural characteristics and solubilization properties of sodium dodecyl sulfate micellar assemblies

The cosurfactant activity of N-glycinylmaleamic acid (NGMA) in sodium dodecyl sulfate (SDS) micelles has been demonstrated. The complementary techniques of electron spin resonance (ESR) and fluorescence spectroscopy have been used to draw information on hydration index (H), microviscosity (eta), and aggregation number (N) of micellar assemblies. The estimate of the critical micelle concentration of SDS in the presence of NGMA suggests a synergistic effect of NGMA. The enhanced solubilization of butyl propionate in the presence of NGMA in SDS micelles is explained on the basis of availability of larger interfacial area calculated from a simple spherical geometric model, combined with a low hydrophilicity index as estimated from ESR. Thus, addition of NGMA contributes to an increase of about 50% in ratio of area of polar shell (AP)/volume of hydration (Vh) ratio. The decrease in H accompanied by a decrease in eta with the incorporation of butyl propionate probably arises from solubilization of a butyl component inside the core with the adsorption of propionate ester on the interface.     

Structure and dynamics of concentrated micellar solutions of sodium dodecyl sulfate

In micellar solutions of sodium dodecyl sulfate, as the concentration of surfactants increases, the spheroid shape of the micelles changes from almost spherical to ellipsoidal with increasing ratio of half-axes ratio, and further the transition to cylindrical micelles occurs. The micelles in an aqueous solution can directly contact (compact aggregates) or be separated from one another by layers of intermicellar medium (periodical colloid structures). In the latter case, the thickness of the layer can significantly exceed the micelle size, and then no mutual correlation in micelle arrangement is observed. According to the data of small-angle X-ray scattering, the relationship between the surfactant concentration and formation of “quasi-crystalline” micellar structure is nonlinear, which can be due to both micelle aggregation processes and nonuniformity of their structure. The possible influence of ordered micellar structures on the diffusion mobility of micelles is shown.     

Prediction of conformational characteristics and micellar solution properties of fluorocarbon surfactants

A molecular-thermodynamic theory is developed to model the micellization of fluorocarbon surfactants in aqueous solutions, by combining a molecular model that evaluates the free energy of micellization of fluorocarbon surfactant micelles with a previously developed thermodynamic framework describing the free energy of the micellar solution. In the molecular model of micellization developed, a single-chain mean-field theory is combined with an appropriate rotational isomeric state model of fluorocarbon chains to describe the packing of the fluorocarbon surfactant tails inside the micelle core. Utilizing this single-chain mean-field theory, the packing free energies of fluorocarbon surfactants are evaluated and compared with those of their hydrocarbon analogues. We find that the greater rigidity of the fluorocarbon chain promotes its packing in micellar aggregates of low curvatures, such as bilayers. In addition, the mean-field approach is utilized to predict the average conformational characteristics (specifically, the bond order parameters) of fluorocarbon and hydrocarbon surfactant tails within the micelle core, and the predictions are found to agree well with the available experimental results. The electrostatic effects in fluorocarbon ionic surfactant micelles are modeled by allowing for counterion binding onto the charged micelle surface, which accounts explicitly for the effect of the counterion type on the micellar solution properties. In addition, a theoretical formulation is developed to evaluate the free energy of micellization and the size distribution of finite disklike micelles, which often form in the case of fluorocarbon surfactants. We find that, compared to their hydrocarbon analogues, fluorocarbon surfactants exhibit a greater tendency to form cylindrical or disklike micelles, as a result of their larger molecular volume as well as due to the greater conformational rigidity of the fluorocarbon tails. The molecular-thermodynamic theory developed is then applied to several ionic fluorocarbon surfactant-electrolyte systems, including perfluoroalkanoates and perfluorosulfonates with added LiCl or NH(4)Cl, and various micellar solution properties, including critical micelle concentrations (cmc's), optimal micelle shapes, and average micelle aggregation numbers, are predicted. The predicted micellar solution properties agree reasonably well with the available experimental results.     

全氟辛酸钠与十二烷基三甲基溴化铵混合胶束微环境性质的NMR,ESR研究

应用表面张力法、NMR法和ESR法研究了全氟辛酸钠(SPFO)-十二烷基三甲基溴化铵(DTAB)混合体系水溶液胶束形成及混合胶束的微环境性质(微观粘度、微观极性等)。结果表明, 碳氟表面活性剂碳氟链和碳氢表面活性剂碳氢链之间具有强烈的相互作用, DTAB与SPFO在水溶液中形成混合胶束。DTAB与SPFO混合体系的表面活性高于单一的DTAB或SPFO, 混合体系cmc较单一的DTAB和SPFO低。DTAB与SPFO混合胶束的微观粘度较DTAB胶束的大, 而微观极性较DTAB的小。     

Analytical micelles containing amphiphilic aminoanthraquinone solvatochromic reporter receptor

The feasibility of using an amphiphilic photoactive derivative of aminoanthraquinone (C18) as both a local solvatochromic probe reporting its position in a micelle and a component of an analytical supramolecular unit in mixed micelles based on a nonionic surfactant, Triton X100, has been considered. The solvatochromism of the 1,8-anthraquinone derivative (C18) has, for the first time, been investigated. Dipole moments of C18 molecules have been determined within the frameworks of the Lippert–Mataga, Kawski, and Reichardt approaches. It has been found that the Δμ values, as calculated with the help of the first two approaches and the Onsager radius, which is, for C18, equal to 5.8 Å, are markedly higher than the value obtained in terms of the Reichardt model. Possible reasons for discrepancies, which arise between experimental data and theoretical predictions when analyzing the solvatochromic properties of dyes, have been briefly discussed. C18 has been employed as an example to show that, for chromophores capable of donor–acceptor interactions, the use of protic solvents is more reasonable, because they ensure realization of a wider spectrum of interactions with a probe, among which the van der Waals interactions play an important role. Therewith, polarization effects, rather than charge separation, make a substantial contribution. In the case of amphiphilic chromophores, “enveloping” of polar groups with hydrocarbon chains decreases the local dielectric permittivity and the probability of intermolecular donor–acceptor interactions (hydrogen bonding). The character of the microenvironment of C18 reporter in micelles has been determined with the use of the “relative polarity parameter” proposed in this work. This parameter makes it possible to compare results obtained for different models of solvatochromism. It has been shown that the characteristics of C18 microenvironment in micelles correspond to those of water–alcohol solutions, with the chromophoric moieties of dye molecules located in the polar region of a micelle, this region being formed by hydrated ethylene-oxide chains of Triton X100. Polar receptor groups of C18, which face the aqueous phase, complete the hydrophilic shell of a micelle, while hydrocarbon chains of both components compose its hydrophobic core. This structure of the normal micelle and the markedly higher intensity of fluorescence of the micellar system than that of an aqueous C18 solution make possible the analytical determination of metal ions in aqueous media.     

From crystal to micelle: A new approach to the micellar structure

The structure of sodium and rubidium deoxycholate micellar aggregates in aqueous solutions was found to be helical and to be stabilized mainly by polar interactions. Astonishingly, the lateral surface of the helix is covered by nonpolar groups and the interior part is filled with cations surrounded by water molecules, as in the case of an inverted micelle. This helical model was inferred from the crystal structures of sodium and rubidium deoxycholates and proved by spectroscopic and diffractometric experimental data. The strategy of the approach to the determination of the micellar structure and the comparison with another model, previously proposed for the bile salt micelles, are reported. On the basis of some results obtained for sodium tauro- and glyco-deoxycholates, micellar models are suggested which could account for the biological function of these important conjugated bile salts.     

A small-angle X-ray scattering study of the structure of lysozyme-sodium dodecyl sulfate complexes

The structure of lysozyme-sodium dodecyl sulfate (SDS) complexes in solution is studied using small-angle X-ray scattering (SAXS). The SAXS data cannot be explained by the necklace and bead model for unfolded polypeptide chain interspersed with surfactant micelles. For the protein and surfactant concentrations used in the study, there is only marginal growth of SDS micelles as they complex with the protein. Being a small and rather rigid protein, lysozyme can penetrate the micellar core which is occupied by flexible and disordered paraffin chains and also the shell occupied by the hydrated head groups. A partially embedded swollen micellar model seems appropriate and describes well the scattering data. The SAXS intensity profiles are analyzed by considering the change in the electron scattering length density of the micellar core and shell due to complexation with protein and treating the intermicellar interaction using rescaled mean spherical approximation (RMSA) for charged spheres.     

A molecular modeling study of pentanol solubilized in a sodium octanoate micelle

In order to study the structural and dynamical aspects of the solubilization process of pentanol within a sodium octanoate micelle a molecular dynamics simulation is presented. In this initial study we discuss the results and detailed insights into the interactions between sodium octanoate, pentanol, and water. The total micellar radius and the hydrophobic core radius were determined. The calculated values are in fairly good agreement with experimental results. In contrast to pure sodium octanoate micelles the aggregate with dissolved pentanol attained a more spherical shape related to the time interval of the simulation. It is clear that the results of a molecular dynamics computer simulation are always limited by its total length and the total time used for data analysis. Nevertheless, from our simulation study it turned out that a part of the pentanol hydroxyl groups were located within the micellar core and some alcohol molecules were also observed at the surface region of the micelle. The corresponding partition coefficient was calculated and agreed well with the experiment. The evaluated radial distribution functions of the sodium ions, the octanoate oxygens, and the hydroxyl hydrogens reveal details of the interface region of the micelle and the bulk phase. Additionally, it was possible to calculate the trans-to-gauche ratios of the alkyl chains and to compare these results with the simulation of a pure octanoate micelle.     

Hexagonal close packing of nonionic surfactant micelles in water

The knowledge of the exact shapes of micelles in various micellar phases found in both lyotropic and thermotropic liquid crystals is very important to our understanding of the underlying principles of molecular self-assembly. In the current paper we present a detailed structural study of the hexagonal close packed (hcp, space group P63/mmc) micellar phase, observed in the binary mixtures of nonionic surfactant C12EO8 and water. The reconstructed electron density map of the phase shows perfectly spherical micelles. A spherical core/shell model of micelles, which fits the observed X-ray diffraction pattern satisfactorily, is subsequently constructed. The results confirm the previous assumption that the hcp phase consists of spherical close contacting micelles, each of which contains a low-density core of aliphatic parts and a high-density shell of hydrated ethylene oxide segments, with the gaps between the micelles filled by pure water.     

Hollow nanoparticles prepared from pH‐responsive template polymer micelles

Water‐soluble crosslinked hollow nanoparticles were prepared using pH‐responsive anionic polymer micelles as templates. The template micelles were formed from pH‐responsive diblock copolymers (PAMPS‐PAaH) composed of the poly(sodium 2‐(acrylamido)‐2‐methylpropanesulfonate) and poly(6‐(acrylamido)hexanoic acid) blocks in an aqueous acidic solution. The PAMPS and PAaH blocks form a hydrophilic anionic shell and hydrophobic core of the core‐shell polymer micelle, respectively. A cationic diblock copolymer (PEG‐P(APTAC/CEA)) with the poly(ethylene glycol) block and random copolymer block composed of poly((3‐acrylamidopropyl)trimethylammonium chloride) containing a small amount of the 2‐(cinnamoyl)ethylacrylate photo‐crosslinkable unit can be adsorbed to the anionic shell of the template micelle due to electrostatic interaction, which form a core‐shell‐corona three‐layered micelle. The shell of the core‐shell‐corona micelle is formed from a polyion complex with anionic PAMPS and cationic P(APTAC/CEA) chains. The P(APTAC/CEA) chains in the shell of the core‐shell‐corona micelle can be photo‐crosslinked with UV irradiation. The template micelle can be dissociated using NaOH, because the PAaH blocks are ionized. Furthermore, electrostatic interactions between PAMPS and PAPTAC in the shell are screened by adding excess NaCl in water. The template micelles can be completely removed by dialysis against water containing NaOH and NaCl to prepare the crosslinked hollow nanoparticles. Transmission electron microscopy observations confirmed the hollow structure. © 2012 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2012     

温度对Pluronic嵌段共聚物胶束结构的影响

温度对Ｐｌｕｒｏｎｉｃ嵌段共聚物Ｆ１０８、Ｆ６８、Ｐ９４和Ｌ６４胶束结构影响的研究结果表明,随着温度上升,胶束外壳ＰＥＯ链的水化度急剧减小,胶束趋于形成聚集更为密实、尺寸较均匀的球形结构。在较高温度时,胶束内核基本上以ＰＰＯ链为主构成。     

A small-angle neutron scattering study of sodium dodecyl sulfate-poly(propylene oxide) methacrylate mixed micelles

Mixed micelle of protonated or deuterated sodium dodecyl sulfate (SDS and SDSd25, respectively) and poly(propylene oxide) methacrylate (PPOMA) are studied by small-angle neutron scattering (SANS). In all the cases the scattering curves exhibit a peak whose position changes with the composition of the system. The main parameters which characterize mixed micelles, i.e., aggregation numbers of SDS and PPOMA, geometrical dimensions of the micelles and degree of ionisation are evaluated from the analysis of the SANS curves. The position q(max) of the correlation peak can be related to the average aggregation numbers of SDS-PPOMA and SDSd25-PPOMA mixed micelles. It is found that the aggregation number of SDS decreases upon increasing the weight ratio PPOMA/SDS (or SDSd25). The isotopic combination, which uses the "contrast effect" between the two micellar systems, has allowed us to determine the mixed micelle composition. Finally, the SANS curves were adjusted using the RMSA for the structure factor S(q) of charged spherical particles and the form factor P(q) of spherical core-shell particle. This analysis confirms the particular core-shell structure of the SDS-PPOMA mixed micelle, i.e., a SDS "core" micelle surrounded by the shell formed by PPOMA macromonomers. The structural parameters of mixed micelles obtained from the analysis of the SANS data are in good agreement with those determined previously by conductimetry and fluorescence studies.     

Partitioning of macrocyclic compounds in a cationic and an anionic micellar solution: a small-angle neutron scattering study

Following a previous investigation on partitioning of some macrocycle compounds in sodium dodecyl sulfate (SDS) and dodecyltrimethylammonium bromide (DTAB) aqueous solutions and their effect on the micellar structure, a small-angle neutron scattering (SANS) study has been performed at fixed surfactant content (0.20 mol/L) and varying macrocycle concentrations from 0.20 up to 1.0 mol/L. Conductivity measurements have been also performed in order to evaluate the effect of the presence of macrocycles on the critical micellar concentration (cmc) of the two surfactants. SANS experimental data were fitted successfully by means of a core-plus-shell monodisperse prolate ellipsoid model. It has been found that 1,4,7,10,13,16-esaoxacyclooctadecane (18C6) and 4,7,13,16-tetraoxa-1,10-diazacyclooctadecane (22) do not interact with DTAB micelles whereas their sodium complexes interact with SDS aggregates and partially localize, as a consequence of electrostatic interaction, on the micellar surface or in the Stern layer. 2,5,8,11,14,17-Hexaoxabicyclo[16.4.0] dicosane (B18C6), as a consequence of the increased hydrophobic character with respect to 18C6, interacts with DTAB hydrocarbon chains and partially localizes in the inner part of micelles. This finding has been successfully used to justify the higher amount of B18C6 compared to the 18C6 one found in the SDS micellar phase. The substituted crown ether has been found localized both on the micelle surface via complex formation and in the inner part of micelles as a consequence of the increased hydrophobic character. For all systems, the aggregate size primarily decreases with the amount of macrocycle in the micellar phase. The interpretation of cmc trends as a function ofmacrocycle concentration gives information on its distribution between micellar and aqueous phases that is in line with SANS results.     

Micellar solubilization of biopolymers in hydrocarbon solvents. I. a structural model for protein-containing reverse micelles

Three proteins (horse liver alcohol dehydrogenase, ribonuclease, lysozyme) were solubilized in hydrocarbon with the help of reverse micelles formed by aqueous di(2-ethyl-hexyl) sodium sulfosuccinate (AOT). Sedimentation and diffusion coefficients of the micellar aggregates were measured with an analytical ultracentrifuge. Partial specific volumes were also evaluated from density measurements. The molecular weight of the protein-containing reverse micelles (M _t ) could thus be determined for each protein system at various w₀ values (w₀ - [H₂O]/[AOT]). For horse liver alcohol dehydrogenase at w₀ = 46.4, for example,M _t is ca. 2,670,000 Daltons; for lysozyme at wo = 22.5,M _t is ca. 323,000 Daltons and increases by increasing w₀. On the basis of these experimentally determined molecular weights, a structural model for the protein-containing reverse micelle is proposed. The model is based upon the assumption that the protein is confined in the water pool of a spherical micelle, and that the inner core volume is the sum of the protein volume and the volume of all water molecules present in a micelle. It is possible then to calculate the micellar structure at each w₀ value. For example, in the case of ribonuclease at w₀ = 20, the inner core radius is ca. 37.5 A, and a layer of water of ca. 22 A separates the protein surface from the surfactant layer. The possible implications of this model for the reactivity of enzymes solubilized in hydrocarbons by reverse micelles are discussed.     

Activity of Subtilisin Carlsberg in macromolecular crowding

Enzymatic activity of a proteolytic enzyme Subtilisin Carlsberg (SC) in anionic sodium dodecyl sulfate (SDS) micellar medium has been explored and found to be retarded compared to that in bulk buffer. Circular dichroism (CD) study reveals that SDS, which is a potential protein denaturant, has an insignificant denaturation effect on SC. The structural integrity of the protein offers an opportunity to study the functionality of the enzyme SC in a macromolecular crowding of micelles. Dynamic light scattering (DLS) data indicates no sandwich-like micelle-SC complex formation ruling out the possibility of interaction of the enzyme with the hydrophobic core of the micelle. However, steady state and time resolved emission studies on specific and nonspecific fluorescent probes indicate the proximity effect at the surface of the enzyme due to macromolecular crowding of the micelles. The agreement of retarded enzymatic activity in the micellar crowd with a theoretical model ascribed to the facts that substrates are compartmentalized in the micelles and enzyme interacts with the micelle through stern layer.     

SDS对SB3-12胶束表面电荷密度的调控作用及对药物增溶的影响

两性离子甜菜碱表面活性剂(SB3-12)胶束具有较好的生物相容性,由于相反电荷的极性头之间具有静电中和作用,胶束表面具有小的负电荷密度。当加入阴离子的十二烷基硫酸钠(SDS)以后,负离子SD-与SB3-12胶束极性区内层季铵正电荷的静电中和作用,能连续地调节胶束表面磺酸基的负电荷密度,这有利于对药物分子的选择性增溶和调节在生理条件下的药物的输送。等温滴定量热(ITC)研究发现SB3-12和SDS有强的协同效应,混合临界胶束浓度(CMC)和胶束化焓明显降低,并得到两者协同效应的弱静电作用机理。当模型药物分子芦丁(Rutin)与SB3-12/SDS混合胶束作用时,芦丁7位羟基的氢解离后的阴离子与SDS共同作用于SB3-12形成混合胶束。UV-Vis吸收光谱和~1H NMR谱研究发现,在SB3-12胶束中,芦丁分子的A环位于季铵阳离子附近,B环位于两个相反电荷之间的弱极性区域。在SDS胶束中,B环位于栅栏层,而A环和二糖暴露于水相侧。在混合胶束中,随着SDS摩尔分数增加,对A环的静电吸引变弱。离子表面活性剂对两性离子表面活性剂胶束表面电荷密度的调节作用,本质上是对胶束极性区域的物理及化学性质的微调,进而实现对药物的可控增溶。