Solubilization in micelles

A very useful property of micellar aggregates is their ability to enhance the aqueous solubility of hydrophobic substances which otherwise are only sparingly soluble in water. The enhancement in the solubility arises from the fact that the micellar cores, for classical low 

For PPO-PEO block copolymer it could be found that the solubilization capacity of the micellar core is correlated to the Flory—Huggins interaction parameter Xs,core which can be expressed in terms of the solubility parameters 65 and Score for the solubilizate s and the core-forming block, respectively  

A good example of the biological relevance of solubilization in micelles is provided by the mechanism by which fats are digested by animals. This is achieved using bile salts, which act as surfactants in the stomach and intestine. Examples of cholesterol derivatives that are bile salts are illustrated in Fig. 4.21. Cholesterol itself is weakly amphiphilic due to the presence of a terminal -OH group (in fact, it is an example of a lipid 

Vesicles and liposomes (vesicles formed by lipids) are also important in solubilization applications, as discussed further in Section 4.11.4. 

The phase behaviour of surfactants at high concentration is described by two types of model. The first is based on the curvature of a surfactant film at an interface. The second is based on the shape of the surfactant molecules themselves. We now consider each of these approaches in turn. 

In the model for interfacial curvature of a continuous surfactant film, we use results from the differential geometry of surfaces. A surface can be described by two fundamental types of curvature at each point P in it mean and Gaussian curvatures. Both can be defined in terms of the principal curvatures c = /R and ci = 1/Ri, where Ri and Ri are the radii of curvature. The mean curvature is 

Radii of curvature for a portion of a so-called saddle surface (a portion of a surfactant film in a bicontinuous cubic structure) are shown in Fig. 4.23, although they can equally well be defined for other types of surface, such as convex or concave surfaces found in micellar phases. To define the signs 

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Surfactants have also been of interest for their ability to support reactions in normally inhospitable environments. Reactions such as hydrolysis, aminolysis, solvolysis, and, in inorganic chemistry, of aquation of complex ions, may be retarded, accelerated, or differently sensitive to catalysts relative to the behavior in ordinary solutions (see Refs. 205 and 206 for reviews). The acid-base chemistry in micellar solutions has been investigated by Drummond and co-workers [207]. A useful model has been the pseudophase model [206-209] in which reactants are either in solution or solubilized in micelles and partition between the two as though two distinct phases were involved. In inverse micelles in nonpolar media, water is concentrated in the micellar core and reactions in the micelle may be greatly accelerated [206, 210]. The confining environment of a solubilized reactant may lead to stereochemical consequences as in photodimerization reactions in micelles [211] or vesicles [212] or in the generation of radical pairs [213]. 

As shown in Fig. 6, the amount of polymerized monomer droplets strongly depends on the emulsifier concentration. With increasing emulsifier concentration, the amount of monomer initially present in the monomer droplets decreases in favor of monomer solubilized in micelles. Concurrently the fraction of polymerized monomer droplets decreases and more microgels are formed. Above a certain emulsifier concentration which is about 0.8 mol/1 in thermal initiation, the monomer is completely solubilized prior to polymerization and no polymerized monomer droplets are formed. 

Continuous aqueous phase emulsion polymerization is one of the most widely used procedures to make nanoparticles for drug delivery purposes, especially those prepared from the alkylcyanoacrylate monomers. An oil-in-water emulsion system is employed where the monomer is emulsified in a continuous aqueous phase containing soluble initiator and surfactant [39, 40]. Under these conditions, the monomer is partly solubilized in micelles (5-10 nm), emulsified as large... 

In contrast to the above results, all three "picket fence" porphyrins are solubilized in an oil-in-water microemulsion to yield a clear solution having a Soret band at 419-421 nm resembling that of H2PF,TPro solubilized in micelles. In this case the microemulsion (composed of SDS, n-pentanol and dodecane) consists of oil "droplets" dissolved in bulk water the radius of the droplet has been estimated to be 37 A ( ), well over twice that estimated for an SDS micelle (16 A). Since the droplet in the microemulsion contains a much larger "interior", it is reasonable that it may be a better medium for solubilizing the porphyrin. 

Emulsion polymerization is applicable only to monomers that are relatively insoluble in water, such as styrene. A coarse emulsion of monomer in aqueous surfactant is prepared with a water-soluble initiator, say, H202 in the solution. The surfactant concentration is above the CMC, so surfactant molecules are present as monomers, micelles, and emulsifiers at the oil-water interface. Even an insoluble liquid like styrene dissolves in water to some extent. Therefore the monomer is present in coarse emulsion drops, solubilized in micelles, and as dissolved molecules in water. A schematic illustration of the distribution of surfactant, monomer, and polymer in an emulsion polymerization process is shown in Figure 8.14. 

FIG. 2 Transport of cholesterol (CHOL) and plant sterols (PS) in the enterocyte. CHOL, PS, and other lipids are solubilized in micelles that deliver the lipids to the brush border membrane. CHOL and PS are transported into the enterocyte by NPC1L1. Nearly all of the PS are redirected back to the intestinal lumen by the transporters ABCG5 and ABCG8. The extent to which CHOL is transported by ABCG5 and ABCG8 is not known. CHOL within the enterocyte is packaged into lipoproteins (chylomicrons) and secreted into lymph and eventually the bloodstream for transport to the liver. 

The cholesterol-lowering properties of dietary plant sterols have been known for decades (Best et al., 1954 Peterson, 1951 Poliak, 1953), due specifically to reductions in cholesterol absorption. Inverse correlations between plant sterol intake and cholesterol absorption have been reported in animals (Carr et al., 2002 Ntanios and Jones, 1999) and humans (Ellegard et al., 2000). The exact mechanism by which plant sterols inhibit cholesterol absorption is unclear, and several mechanisms of action have been proposed, including (1) competition with cholesterol for solubilization in micelles within the intestinal lumen, (2) cocrystallization with cholesterol to form insoluble crystals, (3) interaction with digestive enzymes, and (4) regulation of intestinal transporters of cholesterol. 

Jesch, E.D. and Carr, T.P. 2005. Plant sterols inhibit cholesterol solubilization in micelles. FASEB J. 19, A1011. 

Solubilization in micelles can provide a means of delivering otherwise insoluble drugs or improving the transport of agrochemicals across plant membranes. Some ways in which a substrate can be solubilized by a microemulsion include [236] ... 

Figure 5. Transport through a membrane when solubilizing micelles are present on both sides. The dye may cross as if it were unsolubilized (bottom) and perhaps also solubilized in micelles (middle). Monomeric surfactant may also cross (top) but does not affect dye transport...

This review will focus on a variety of photochemical reactions which have been studied in micellar solutions, and will show how the micelle affects the outcome of these reactions. Photochemical reactions can be altered by solubilization into micellar solutions, such that the products or the relative yield of products can change relative to homogeneous solution. Furthermore, an increase or decrease in the dynamics or the efficiencies of photochemical reactions may also occur upon solubilization in micelles. 

By use of the Taylor dispersion method, diffusion coefficients for pyrene solubilized in micelles of octadecyltrimethylammonium chloride (CigTAC) and tetradecyltrimethyl-ammonium bromide (C14TAB) have been measur in aqueous NaCl and NaBr solutions, respectively, at 35 °C. These values can be regarded as tracer diffusion coefficients for the micelles b use essentially all pyrene molecules are solubilized in the micelles. In the range... 

AU discussions of particle nudeation start with the Smith-Ewart theory in which Smith and Ewart (1948) in a quantitative treatment of Harkins micellar theory (Harkins, 1947, 1950) managed to obtain an equation for the particle number as a function of emulsifier concentration and initiation and polymerization rates. This equation was developed mainly for systems of monomers with low water solubility (e.g., styrene), partly solubilized in micelles of an emulsifier with low critical micelle concentration (CMC) and rseeited to work well for such systems (Gerrens, 1963). Other authors have, however, argued against the Smith-Ewart theory on the grounds that (i) particles are formed even if no micelles are present, (ii) the equation for the... 

Monomer (i) will usually exist as monomer droplets (ii) some monomer, depending on water solubility, will be dissolved in the continuous phase and (iii) some monomer will be solubilized in micelles. 

It was noted that activity and conformation change with the amount of water inside micelles, pointing out the importance of the aqueous environment, easily adjustable as a function of the water content, which is impossible when studies are performed in aqueous solutions. Furthermore, because many properties (9) of the water core resemble those of water present at interfaces in biological systems, reversed micelles provide an excellent system for studying the interactions between polypeptides and interfacial water (10-11) or more generally their conformation when solubilized in micelles (12-15), depending on where the biopolymer is located inside the micelle and what its conformation is. 

The method is based on the observation that chromophore-containing solutes undergo significant shifts in their UV spectra upon solubilization in micelles. The experimentally determined molar absorbance of a solute at a given wavelength in a micellar solution, E, will be an average value of the molar absorbance of the molecules in the micellar and the aqueous phase. 

If we look at the absolute values of partial molar volumes and compressibilites of alcohols solubilized in micelles, it appears that for the lower alcohols, up to heptanol, volumes and compressibilities exhibit lower values in SDS than in carboxylates. It also appears that the partial molar compressibilities of these alcohols are higher than the molar compressibility of the pure alcohols when solubilized in the carboxylate micelles and lower when solubilized in SDS. 

With appropriate values of the various parameters, this model yielded predictions in good agreement with experiment on such phenomena as the amounts of various pure hydrocarbons solubilized in micelles of sodium dodecyl sulfate SDS as well as the amounts of benzene and -hexane solubilized in the same micelles from various mixtures of the two hydrocarbons. It was also able to predict transformation of rodlike micelles to spherical microemulsion droplets as a result of hydrocarbon solubilization, an effect that has been observed experimentally. In the absence of hydrocarbon, films of these surfactants can attain their preferred curvatures only by forming cylindrical micelles, as micelle radius is limited to the extended length of a surfactant molecule. However, when considerable hydrocarbon is present, this constraint no longer applies, and spherical microemulsion droplets can grow until the preferred curvature is reached. 

Fig. 25. Frequency dependence of the water 2H longitudinal (circles) and transverse (filled squares) relaxation rates in an aqueous solution of bR solubilized in micelles of n-octyl-/)-D-glucoside at 4°C.The broken line refers to the relaxation rate of the bulk water, while the continuous curve results from a fit to the data of a biLorentzian function as described in the text.139 Reproduced with permission from Academic Press Ltd.

The orientation and concentration of molecules solubilized in micelles may lead to substantial changes in the kinetics of chemical interaction of solubilized molecules with each other and with other substances dissolved in the medium. In some cases solubilization causes a substantial increase in the rate of chemical interaction, which is the basis of micellar catalysis. 

Solubilization Media. Many investigations have been reported on the interaction between a solubilizate and a micellar system. Several solubilization media can constitute interesting drug delivery systems. In other cases, solubilization in micelles represents a simplified model for mimicking interactions with biological membranes as an alternative to bicelles, liposomes and PL bilayers. 

Organic Materials. Qrganic materials that have low water solubihty can be solubilized in micelles to produce systems with substantial organic content where no solubility would occur in the absence of micelles. More details on the phenomenon of solubilization in surfactant micelles will be presented below. In any case it is usually found that immiscible hydrophobic materials will have relatively little effect on cmc, although evidence for shght decreases has been reported. 

Ekwall, R, Mandell, L., and Fontell, K., Solubilization in micelles and mesophases and the transition from normal to reversed structures. Mol. Cryst. Liqd. Cryst, 8, 157, 1969. 

Substances that are solubilized in surfactant micelles can be separated by ultrafiltration through membranes whose pores are smaller in diameter than the micelle size. For a membrane molecular weight cutoff from 1 to 50kDa, the rejections are 98%. The stream of water-containing monomeric molecules of surfactant (permeate) flows through the membrane. The remaining solution (retentate) contains solutes solubilized in micelles. The MEUF process is used for the separation of organic substances and various ions, the latter after their previous complexation. 

Son et al. underlined the dilSculties in deciphering signals characteristic for proteins and for lipids and therefore suggested a q-titration of long-chain and short-chain lipids that allows differentiation between structured and mobile residues of membrane proteins. The term q-titration refers to the comparison of signal intensities in solution NMR spectra of uniformly labeled membrane proteins solubilized in micelles and isotropic bicelles as a function of the molar ratios (q) of the long-chain lipids e.g. DMPC) to short-chain lipids e.g. DHPC). 

Micellar solutions and microemulsions are also used for parenteral delivery of hydrophobic drugs. They are usually stabilized by large amounts of hydrophilic surfactants, such as bile salts and polysorbates. Owing to their small size, micelles are less readily recognized by the immune system, resulting in prolonged circulation [36]. An example of micellar formulation is Taxol , in which the active antitumor agent paclitaxel is solubilized in micelles of polyoxyl castor oil. 

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