Stability Of Mixed Micelles Research Articles

Mixed Micellization of Ionic and Nonionic Surfactants in Aqueous Solution

Mixed micelles of binary surfactant mixtures consisting of nonionic/nonionic and cationic/nonionic surfactants have been prepared in different compositions of the components in aqueous solution in order to study their stability and ideality. Interfacial adsorption, minimum area per surfactant molecule at the interface, thermodynamics of micellization, and stability of mixed micelles have been investigated. The surfactant‐surfactant interaction in the mixed micelle has been determined employing regular solution theory to interpret the experimental findings. Effect of chain length of hydrophobic and hydrophilic moiety on the stability of mixed micelles has been included in the present study.

NMR study of the tetrameric KcsA potassium channel in detergent micelles

Nuclear magnetic resonance (NMR) studies of large membrane-associated proteins are limited by the difficulties in preparation of stable protein-detergent mixed micelles and by line broadening, which is typical of these macroassemblies. We have used the 68-kDa homotetrameric KcsA, a thermostable N-terminal deletion mutant of a bacterial potassium channel from Streptomyces lividans, as a model system for applying NMR methods to membrane proteins. Optimization of measurement conditions enabled us to perform the backbone assignment of KcsA in SDS micelles and establish its secondary structure, which was found to closely agree with the KcsA crystal structure. The C-terminal cytoplasmic domain, absent in the original structure, contains a 14-residue helix that could participate in tetramerization by forming an intersubunit four-helix bundle. A quantitative estimate of cross- relaxation between detergent and KcsA backbone amide protons, together with relaxation and light scattering data, suggests SDS-KcsA mixed micelles form an oblate spheroid with approximately 180 SDS molecules per channel. K(+) ions bind to the micelle-solubilized channel with a K(D) of 3 +/- 0.5 mM, resulting in chemical shift changes in the selectivity filter. Related pH-induced changes in chemical shift along the "outer" transmembrane helix and the cytoplasmic membrane interface hint at a possible structural explanation for the observed pH-gating of the potassium channel.

Adsorption dynamics of binary mixture of Gemini surfactant and opposite-charged conventional surfactant in aqueous solution

The maximum bubble pressure technique has been used to study the adsorption kinetics of binary mixtures of an anionic Gemini surfactant C9 pPHCNa with a cationic conventional surfactant C 10TABr in aqueous solutions. The dynamic surface tension data were analyzed using the revised Ward and Tordai equations as well as the micelle dissociation kinetic model suggested by Joos et al. The apparent diffusion coefficient D a below the cmc, the adsorption barrier ε a and the micelle dissociation constant k mic were obtained. The D a s at short times and at long times were respectively 0.2 – 16 × 10 10 and 0.08 – 0.9 × 10 10 m 2 s −1 , the latter corresponded to the adsorption barrier ε a of 10–20 kJ mol −1. The minimum ε a appeared at the mole fraction of C9 pPHCNa ( α 1 , on a surfactant-only basis) in the bulk solution being 0.33. The k mic s of the mixed micelles were about 16–2300 s −1. The most stable mixed micelles were formed at α 1 = 0.2 rather than at α 1 = 0.33 owing to great discrepancy of hydrophobicity between the two components. These results indicated that the composition of mixed solution was an important factor affecting the adsorption kinetics and the micelle stability.

The influence of bile salts and mixed micelles on the pharmacokinetics of quinine in rabbits

The bioavailability of orally administered drugs can be influenced by interactions with food components and by physico-chemical conditions in the upper gastrointestinal tract. Normally, bile salts enhance the transport of lipophilic drugs across mucosal membranes. Bile salts are able to form stable mixed micelles consisting of fatty acids and phospholipids. Conventional micellar systems are known to solubilize lipophilic drugs having a low bioavailability. The influence of bile salts and mixed micelles on the pharmacokinetics of the lipophilic drug quinine was investigated in rabbits. Female rabbits were given intraduadenally quinine (5 mg/kg body weight) without and with incorporation into the micellar or mixed micellar systems. Blood was collected every 30 min for 6 h. In plasma, concentration of quinine was measured using HPLC. The plasma concentration–time profiles of quinine were significantly lower within the first 2 h after administration in presence of both the sodium salt of glycodeoxycholic acid (above the critical micellar concentration) as well as of mixed micellar systems consisting of glycodeoxycholic acid and palmitic acid and/or lecithin. The pharmacokinetic parameters AUC (relative bioavailability) and c max of quinine were significantly decreased by micellar systems in rabbits. These mixed micellar systems lower and not as expected, increase the absorption of quinine in vivo. Therefore, quinine should be orally administered at least 1 h before food intake, particularly before fat intake.

High-temperature synthesis of stable ordered mesoporous silica materials by using fluorocarbon-hydrocarbon surfactant mixtures.

Highly ordered hexagonal mesoporous silica materials (JLU-20) with uniform pore sizes have been successfully synthesized at high temperature (150-220 degrees C) by using fluorocarbon-hydrocarbon surfactant mixtures. The fluorocarbon-hydrocarbon surfactant mixtures combine the advantages of both stable fluorocarbon surfactants and ordered hydrocarbon surfactants, giving ordered and stable mixed micelles at high temperature (150-220 degrees C). Mesoporous JLU-20 shows extraordinary stability towards hydrothermal treatment (100 % steam at 800 degrees C for 2 h or boiling water for 80 h), thermal treatment (calcination at 1000 degrees C for 4 h), and toward mechanical treatment (compressed at 740 MPa). Transmission electron microscopy images of JLU-20 show well-ordered hexagonal arrays of mesopores with one-dimensional (1D) channels and further confirm that JLU-20 has a two-dimensional (2D) hexagonal (P6 mm) mesostructure. 29Si HR MAS NMR spectra of as-synthesized JLU-20 shows that JLU-20 is primarily made up of fully condensed Q4 silica units (delta=-112 ppm) with a small contribution from incompletely cross-linked Q3 (delta=-102 ppm) as deduced from the very high Q4/Q3 ratio of 6.5, indicating that the mesoporous walls of JLU-20 are fully condensed. Such unique structural features should be directly attributed to the high-temperature synthesis, which is responsible for the observed high thermal, hydrothermal, and mechanical stability of the mesoporous silica materials with well-ordered hexagonal symmetry. Furthermore, the concept of "high-temperature synthesis" is successfully extended to the preparation of three-dimensional (3D) cubic mesoporous silica materials by the assistance of a fluorocarbon surfactant as a co-template. The obtained material, designated JLU-21, has a well-ordered cubic Im3m mesostructure with fully condensed pore walls and shows unusually high hydrothermal stability, as compared with conventional cubic mesoporous silica materials such as SBA-16.

Gadolinium-Containing Mixed Micelle Formulations: A New Class of Blood Pool MRI/MRA Contrast Agents

Because cardiovascular diseases have been the leading cause of death in the United States and Europe since 1900, it is evident that there is a medical need for noninvasive diagnostic procedures for the detection and assessment of coronary artery disease. In the future, magnetic resonance coronary angiography could be an alternative procedure to the largely used but invasive x-ray coronary angiography. In today’s health care environment, an alternative procedure offering the same information at a substantially lower degree of invasiveness and at a fraction of the cost would probably be capable of overcoming even strong resistance to change. A major problem is related to spatial resolution; to improve it, the use of an efficient contrast agent is necessary. Several products have been proposed and studied as blood pool contrast agents for magnetic resonance angiography (MRA), in particular gadolinium chelates bound to albumin (1), polylysine, dextran or carboxydextran (2), and dendrimers (3). Other approaches investigated included magnetites (4–6) and albumin-binding agents (7). The use of liposomes as MR contrast agents has also been evaluated and described by various authors in recent years (8). Contrast agents entrapped within the internal aqueous space of liposomes (9), as well as liposomes incorporating lipophilic contrast agents in the lipid bilayer (10,11), have been prepared and tested. When chelates such as gadopentetate dimeglumine (Gd-DTPA), gadobenate dimeglumine (Gd-BOPTA), and gadoteridol (GdHP-DO3A) are entrapped within the internal aqueous space of lipid vesicles, the main target is the liver (Kupffer cells), and clearance of gadolinium is slow (12). While investigating blood vessels and the possibility of using these liposomes for MRA application, it was observed that their enhancement capacity is limited because the relaxivity of liposomes entrapping gadolinium chelates is about two to five times lower than that of the free gadolinium chelate in solution. It was also observed that the relaxivity depends on the size of the liposomes, with smaller vesicles showing higher relaxivity than larger ones. We are proposing a new approach based on mixed micelle formulations. Physically stable mixed micelle formulations can be obtained by mixing a lipophilic gadolinium chelate, a phospholipid (or phospholipids), and a surfactant. In this way, the relative concentration of gadolinium can be strongly increased compared to liposomes because the physical stability of the mixed micelles is easily achieved with relatively low amounts of lipids and surfactants. It is a large advantage compared to liposomes, for which the relative weight ratio of the lipophilic gadolinium chelate to the other lipids forming the liposome membrane has to be low (10%–20%) to obtain physically stable vesicles. Moreover, with mixed micelles, all gadolinium ions are exposed to the outside and can interact directly with water molecules.

Interaction, Stability, and Microenvironmental Properties of Mixed Micelles of Triton X100 and n-Alkyltrimethylammonium Bromides: Influence of Alkyl Chain Length

Micellar properties of binary surfactant systems of Triton X100 (TX100) with three different n-alkyltrimethylammonium bromides (n = 12 (DTAB), 14 (TTAB), and 16 (CTAB)) were investigated by the fluorescence probe technique. The critical micelle concentration (cmc) values of the corresponding mixtures in the whole range of composition were obtained by the pyrene 1:3 ratio method. In order to estimate the interaction between the surfactants in the mixed micelles, the cmc data were treated by using the conventional regular solution approach for mixed micelles. It was found that whereas the interaction parameter values (β12) remained fairly constant for the TX100−TTAB and TX100−CTAB systems, the TX100−DTAB system was not well modeled by using that theory. However, in all cases the results showed deviation from ideal behavior. The stability of the mixed micelles was also discussed in the light of Maeda's treatment (J. Colloid Interface Sci. 1995, 172, 98), and the observed differences between the three systems were justified on the basis of a certain steric factor due mainly to the presence of the phenyl group of TX100 in connection with the length of the monomer of the cationic component. The micropolarity of the mixed aggregates was examined by the pyrene 1:3 ratio index in micellar solutions of concentration well above the cmc. It was observed that the increasing participation of the ionic component induces the formation of more closed micelles with a more dehydrated structure. The polarized fluorescence measurements, by using diphenylbutadiene as a probe, were interpreted by using the wobbling in cone model. It was found that the order parameter decreases as the participation of the cationic surfactant in the micelle increases, indicating the formation of a less ordered structure than that of pure TX100 micelles. Data obtained in this investigation allowed to establish a clear correlation between micellar stability and microenvironmental properties of the mixed aggregates.

Analysis of Polydispersity of Mixed Micelles of TX-100/SDS and C12E8/SDS by Capillary Electrophoresis

Capillary electrophoresis (CE) was used to study the polydispersity of TX-100/SDS and C12E8/SDS micelle systems. Compared with other techniques, CE provides more specific and graphically detailed information on the compositional polydispersity of such micellar systems. Clear evidence of the coexistence of micelles rich in either nonionic or anionic component has been obtained. This coexistence is explained by considering that the stability of mixed micelles is affected by several factors, including counterion binding, and steric shielding of the electrostatic repulsive interaction among the headgroups of SDS by the bulky EO groups of TX-100. Due to these two factors, micelles with different compositions may be energetically equivalent, leading to a broad distribution of micelle size and composition. In this study, we observe how the pattern of the distribution changes with the mole fraction of SDS. Electrophoretographic patterns also showed that broader compositional distribution of the original components produces a wider distribution of mobilities.

Transport of monooleoylglycerol mediated by bile salt micelles across porous membranes

In order to study how the bile salts and lipids behave in the vicinity of microvillus, the transport properties of a sodium salt of deoxycholic acid (NaDC) and its mixture with monooleoylglycerol (MO) through artificial membranes were investigated in 0.15 M NaCl saline solution at 37°C. The hydrodynamic radius of MO-solubilized micelles was estimated to be approximately 17–20 A from the transport study. The thermodynamically stable MO-NaDC mixed micelles formed above critical micelle concentration in the higher region of mole fraction of NaDC in the mixture (X NaDC>ca. 0.6), can behave as a single species in transport process and freely pass through the porous membranes of both pore sizes, 0.01 μm and 0.1 μm. The permeabilities of MO-NaDC mixed micelles are large compared with those of pure NaDC micelles. MO molecules solubilized may probably enhance the interaction between MO and NaDC molecules by better contacting with the respective hydrophobic groups in a mixed micelle (the flexible structure of MO molecule enables it), and in this situation, the smaller micelles compared with those of pure NaDC must be more favorable.

Mixed micelles as a proliposomal, lymphotropic drug carrier.

Four lipophilic, low molecular weight drugs solubilized in phosphatidylcholine-bile salt mixed micelles were injected s.c. into the hind legs of sheep and their cumulative recoveries in lymph draining from the site of application were determined. Surprisingly, the cumulative recoveries (percentage of dose) varied between less than 1 and 60%. We found that there is a correlation between the lipophilicity of the drug (log P octanol/water approximately Rm degrees value) and the proportion of the dose absorbed by the lymphatic route. Drugs with Rm degrees values greater than 10 are absorbed preferentially by the lymphatics (greater than 50% of dose), whereas compounds with Rm degrees values less than 4 are hardly absorbed at all by the lymphatics (less than 10% of dose). By applying the prodrug principle we demonstrated that it is also possible to target drugs with Rm degrees values less than 4 to the lymphatics. Furthermore, the analysis of the collected lymph samples by gel filtration, quasi-elastic light scattering, and electron microscopy revealed that, following s.c. administration, mixed micelles are converted into homogeneous, unilamellar vesicles. In conclusion, these results suggest that mixed micelles may represent a suitable delivery system for low molecular weight drugs whose targets are lymphoid cells. In addition, for drugs where liposomal application leads to a therapeutic advantage, the thermodynamically stable mixed micelle could be a good alternative to the liposome. However, for both applications a high drug lipophilicity is a prerequisite.

Kinetics and thermodynamics of dissolution of lecithin by bile salts.

The kinetics of dissolution of dispersions of egg phosphatidylcholine (lecithin) by bile salts was studied by observing the decrease in turbidity as mixed micelles of lecithin and bile salts were formed. The rate of dissolution of lecithin corresponding to formation of mixed micelles was studied in the presence of dihydroxy bile salts, sodium deoxycholate, sodium chenodeoxycholate, sodium ursodeoxycholate and one trihydroxy bile salt, sodium cholate. The rate of dissolution of lecithin and mixed micelle formation decreased in the order: chenodeoxycholate greater than deoxycholate greater than cholate greater than ursodeoxycholate. Kinetic solvent isotope studies in D2O, along with measurement of enthalpies of mixed micelle formation both in H2O and D2O, suggest that formation and stabilization of mixed micelles are related to "hydrophobicity" as estimated by high performance liquid chromatography retention factors.

Preparation of monodisperse vesicles with variable size by dilution of mixed micellar solutions of bile salt and phosphatidylcholine

We have investigated by means of quasi-elastic light scattering the aggregative behavior of aqueous mixed micellar solutions of glycocholate and phosphatidylcholine. Upon dilution with buffer the micellar size and the polydispersity increases dramatically, and, as the system is diluted beyond the mixed micellar phase boundary, a spontaneous transition from polydisperse micelles to monodisperse vesicles occurs. The radius of the vesicles formed upon dilution depends strongly upon the final composition of the solution and can be varied between 120 and 550 Å. In contrast to the thermodynamically stable mixed micelles these vesicle solutions can be brought into a metastable state in which it is possible to remove by dialysis the bile salt molecules from the mixed vesicles without changing their radius by more then 10%. The combination of dilution and dialysis thus represents a method for the preparation of unilamellar, monodisperse and detergent-free vesicles with a desired radius that can be chosen between 120 and 500 Å.

Kinetics and thermodynamics of the formation of mixed micelles of egg phosphatidylcholine and bile salts.

The kinetics of dissolution of dispersions of egg phosphatidylcholine (lecithin) by bile salts was studied by observing the decrease in turbidity as mixed micelles of lecithin and bile salt were formed. The rate of dissolution of lecithin corresponding to the formation of mixed micelles was studied in the presence of dihydroxy bile salts, sodium deoxycholate, sodium chenodeoxycholate, sodium ursodeoxycholate, and one trihydroxy bile salt, sodium cholate. The rate of dissolution of lecithin and mixed micelle formation decreased in the order: chenodeoxycholate greater than deoxycholate greater than cholate greater than ursodeoxycholate. Kinetic solvent isotope studies in D2O, along with measurement of enthalpies of mixed micelle formation both in H2O and D2O, appear to indicate that the formation and stabilization of mixed micelles is related to "hydrophobicity" as estimated by high performance liquid chromatography retention factors.

O-95) - Stability of mixed micelle in bile from mice fed a diet containing 1% cholic acid

O-95) - Stability of mixed micelle in bile from mice fed a diet containing 1% cholic acid

Solubilization of homopolymers and copolymers by block copolymer micelles in dilute solutions

AbstractSolubilization by micelles of a three‐block copolymer poly(styrene‐butadiene‐styrene) with a polybutadiene core was studied by the light scattering method on three types of solubilizate: polybutadiene with (a) low and (b) high molar mass (with respect to the polybutadiene block of the copolymer), and (c) a block copolymer poly(styrene‐butadiene‐styrene) with a high content of butadiene. True solubilization of polybutadiene into the cores of spherical micelles occurs in case (a); in case (b) polybutadiene forms partially stabilized, emulsion‐like large droplets. In case (c) stable mixed micelles are formed having either lower or higher molar mass with respect to that of the original micelles, depending on the ratio of molar masses and on the composition of both copolymers. A similarity between solubilization of hydrocarbons by micelles of soaps or surfactants in aqueous solutions and solubilization of polymers by copolymer micelles in selective solvents is pointed out.

The equilibrium and structure of lecithin-cholate mixed micelles

The nature of the equilibrium: mixed micelles-intermicellar solution, has been determined for the system Lecithin-Sodium Cholate. The composition of the intermicellar solution has been estimated after light scattering data, and the results confirmed by other methods. The composition and size of the mixed micelles have then been evaluated. Provided that the mixed micelles are in equilibrium with a solution containing at least the CMC of cholate, their size was shown to diminish progressively as the ratio Lecithin/Cholate present in the mixed micelles decreased. At the same time the concentration of the free cholate dissolved in the intermicellar solution, in equilibrium with the mixed micelles, was shown to increase continuously as the size of the mixed micelles decreased. The thermodynamic equilibrium of these systems has been treated in a simple manner. The existence of stable mixed micelles in equilibrium with a free cholate concentration below the CMC was seen to correspond to a metastable state, and in the presence of small amounts of salt such systems immediately coagulated. Finally it is shown that the proposed model satisfactorily accounted for the variation in size of the mixed micelles with the micellar Lecithin/Cholate ratio.