Krister Thuresson

Binding of surfactants to hydrophobically modified polymers

Recent progress in the understanding of the binding of surfactants to hydrophobically modified polymers (HMP), and the consequences of such binding, is reviewed. HMP are water-soluble polymers onto which low proportions of hydrophobic sidechains (hydrophobes) have been grafted. In an aqueous environment, the HMP hydrophobes associate among themselves and with added surfactant molecules into micelle-like aggregates. An HMP may therefore be considered as a ‘modified surfactant’, and the binding of surfactants to HMP is analogous to the mixed micellisation in mixed surfactant solutions. The binding isotherm gives the concentration of free (monomeric) surfactant and the stoichiometry of the HMP/surfactant complex at different total compositions. In mixtures involving ionic surfactants, it is found that the free surfactant often dominates, and gives important contributions to the ionic strength. Characteristic properties of HMP/surfactant mixtures may be related to stoichiometries of the mixed complexes. Thus, the maximum in solution viscosity, which is commonly found in HMP/surfactant mixtures, occurs at a similar hydrophobe stoichiometry (ratio of bound surfactant to HMP hydrophobe) for many different systems, although the total concentrations of surfactant at the maximum may vary by orders of magnitude, depending on the surfactant cmc. The solubility of a complex of oppositely charged HMP and surfactant is related to the charge stoichiometry of the complex. The phase separation/redissolution phenomena occurring in the bulk solution influence the HMP adsorption to surfaces and the forces between surfaces with adsorbed HMP.

A water gradient can be used to regulate drug transport across skin

At normal conditions there is a substantial water gradient over the skin as it separates the water-rich inside of the body from the dry outside. This leads to a variation in the degree of hydration from the inside to the outside of skin and changes in this gradient may affect its structure and function. In this study we raise the question: How do changes in the water gradient across skin affect its permeability? We approach this problem in novel diffusion experiments that permit strict control of the gradient in the chemical potential of water and hence well-defined boundary conditions. The results demonstrate that a water gradient can be used to regulate transport of drugs with different lipophilic characteristics across the skin barrier. It is shown that the transport of metronidazole (log P(o/w)=0.0) and methyl salicylate (log P(o/w)=2.5) across skin increases abruptly at low water gradients, corresponding to high degrees of skin hydration, and that this effect is reversible. This phenomenon is highly relevant to drug delivery applications due to its potential of temporarily open the skin barrier for transdermal drug delivery and subsequently close the barrier after treatment. Further, the results contribute to the understanding of the occlusion effect and indicate the boundary conditions of the water gradient needed to make use of this effect.

Microemulsions in amphiphilic and polymer-surfactant systems

Microemulsions may have very different microstructures: discrete water or oil droplets and bicontinuous — depending, inter alia, on the surfactant polarity, salinity, temperature, and co-surfactant. A review is given on structure determination of microemulsions of different systems and the conditions for occurrence of different structures. Polymer addition may dramatically influence microemulsion stability and structure and examples are given for different types of polymers and discussed on the basis of mixed solutions of polymers and surfactants in general.

Mixed solutions of surfactant and hydrophobically modified polymer

The properties of mixed solutions of surfactants and hydrophobically modified polymers are reviewed, with a special emphasis on molecular interpretations. Aspects covered include self-assembly and mixed aggregation, phase behaviour, rheology, and interfacial behaviour. Copyright

Interactions between chitosan-modified particles and mucin-coated surfaces.

Lipid-based particles (Cubosome particles) were surface-modified by chitosan and the ratio between particles and chitosan was optimized to minimize the free chitosan concentration in the dispersion. The modified particles were characterized by electrophoretic measurements and the pH dependence of the zeta potential could be directly related to the protonation of chitosan. Interaction between the modified particles and mucin-coated silica surfaces were subsequently investigated in situ by ellipsometry to assess the mucoadhesive properties at physiologically relevant conditions. The result showed that a substantial amount of modified particles was adsorbed to mucin-coated silica surfaces at both pH 4 and pH 6, probably due to electrostatic interactions between amino groups in chitosan and negatively charged groups in mucin. Furthermore, the amount of bound particles decreased by less than 15% upon rinsing indicating relatively strong interactions. This investigation demonstrates that ellipsometry is a useful tool to study mucoadhesive properties of particles in the submicrometer range. Moreover, the novel chitosan-modified particles may be of interest for mucosal drug delivery applications.

Interactions between Drug Delivery Particles and Mucin in Solution and at Interfaces

Cubosome particles were produced by fragmenting a cubic crystalline phase of glycerol monooleate and water in the presence of a stabilizing poly(ethylene oxide)-based polymer. The aim of our investigation was to study the interaction between these particles and mucin to gain information on how they would perform as a vehicle for mucosal drug delivery. Particle electrophoresis was used to investigate the interactions between particles and mucin in solution, and ellipsometry was utilized to study the interactions between particles and mucin-coated silica surfaces. The interaction studies were performed at relevant physiological conditions, and the pH and ionic strength were varied to gain more information about the driving forces for the interaction. The results from electrophoretic measurements showed that mucin in solution adsorbed to the particles at pH 4, whereas at pH 6 no clear interaction was detected. From ellipsometric measurements it was evident that the particles adsorb reversibly to a mucin-coated silica surface at pH 4, while no adsorption of particles could be detected at pH 6. The overall conclusion is that the interaction between these particles and mucin is weak and pH-dependent. These findings are in agreement with other investigations of the interactions between mucin and poly(ethylene oxide) chains.

A rheological investigation of the complex formation between hydrophobically modified ethyl (hydroxy ethyl) cellulose and cyclodextrin

The thickening effect of a hydrophobically modified polymer in an aqueous solution is dependent on intermolecular hydrophobic associations, and if the polymer concentration is significantly above the overlap concentration also on chain entanglements. In this investigation we have added different cyclodextrins (CD) in order to decouple hydrophobic polymer-polymer associations via inclusion complex formation with the polymer hydrophobic tails. Both size and hydrophobicity of the cavity of the CD-molecules were found to have an effect on the process. In addition, the influence of chemical structure of the polymer hydrophobic tails was investigated. Either a linear C-14-chain or a more bulky nonylphenol group was used. The viscosity as a function of CD-concentration first decreased strongly, and then attained a constant value. At excess CD the viscosity became virtually the same as in a solution of the unmodified parent polymer, provided that complex formation was not sterically bindered. This suggests that all hydrophobic links, originating from the hydrophobic modification process, which influence the theology could be deactivated. On the other hand, with combinations where the complex formation was hindered to a certain degree the initial decrease was less accentuated, and also, the viscosity leveled out at a significantly higher value. In an attempt to rationalize the data a simple model based on the assumption that each complex formed deactivates one theologically active link was used. In combination with the Langmuir adsorption model the number of complexes as a function of CD concentration could be obtained. This model also gave a value of the complex formation constant. Furthermore, in solutions where all hydrophobic links could be deactivated the results from the model suggested that all polymer hydrophobic tails were originally active in forming the network

Phase behavior and rheology in water and in model paint formulations thickened with HM-EHEC: influence of the chemical structure and the distribution of hydrophobic tails

Abstract The phase behavior and rheology of aqueous solutions of hydrophobically modified ethyl(hydroxyethyl) cellulose have been investigated. Effects of variations in the chemical structure of the hydrophobic tails grafted to the polymer backbone were followed. When the length of the polymer hydrophobic tails was increased the effects caused by association between different polymer chains became more pronounced. This was manifested by an increased tendency of the solution to phase separate, a higher viscosity, and a more elastic rheological response. The higher elasticity and viscosity was ascribed to slower polymer dynamics following from stronger hydrophobic associations. A separation of chemically different polymer chains into two coexisting phases was strongly promoted by modification with long hydrophobic tails. It was found that one of the coexisting phases contained highly substituted polymer chains, while in the other phase, less substituted polymer chains were found. It is proposed that this type of phase separation occurs because the highly substituted polymer chains have a pronounced tendency to form a network. Model paint formulations prepared with the different polymers showed that an increasing length of the polymer hydrophobic tails slowed down the dynamics of the formulation. This was manifested as a higher thickening efficiency (a smaller amount of polymer material was needed to obtain the desired viscosity), and a more pronounced shear-thinning behavior of formulations comprising polymers with long hydrophobic tails. Compared to the simpler systems, which only contained polymer and water, the model paint formulations were less prone to phase separation. It is suggested that, in the paint formulation, surfactants, latex particles, pigment, and fillers increase the number of possible association sites for the polymer hydrophobic tails.

Glycerol and urea can be used to increase skin permeability in reduced hydration conditions.

The natural moisturizing factor (NMF) is a group of hygroscopic molecules that is naturally present in skin and protects from severe drying. Glycerol and urea are two examples of NMF components that are also used in skin care applications. In the present study, we investigate the influence of glycerol and urea on the permeability of a model drug (metronidazole, Mz) across excised pig skin membranes at different hydrating conditions. The degree of skin hydration is regulated by the gradient in water activity across the membrane, which in turn depends on the water activity of the formulation in contact with the skin membrane. Here, we determine the water activity of all formulations employed using an isothermal calorimetric method. Thus, the gradient in water activity is controlled by a novel experimental set-up with well-defined boundary conditions on both sides of the skin membrane. The results demonstrate that glycerol and urea can retain high steady state flux of Mz across skin membranes at dehydrating conditions, which otherwise would decrease the permeability due to dehydration. X-ray diffraction measurements are performed to give insight into the effects of glycerol and urea on SC molecular organization. The novel steady state flux results can be related to the observation that water, glycerol, and urea all affect the structural features of the SC molecular components in a similar manner.

Surfactant binding and micellisation in polymer solutions and gels: binding isotherms and their consequences

Transient networks are formed by many pairs of polymer and surfactant that associate into mixed micelles. Generally, for a given polymer concentration, the viscosity or the elastic shear modulus of such mixtures first increases and then decreases with the concentration of added surfactant. We point to the importance of considering the general features of the isotherm for the binding of the surfactant to the polymer when analysing these effects. We argue that a break-down of mixed micellar crosslinks between polymers should typically occur only when the added surfactant dominates in the mixed micelles. At this point, the concentration of monomeric surfactant should be of the same order as the relevant c.m.c. of the surfactant. The relevant c.m.c. is not generally the bulk c.m.c. but, rather, the c.m.c. in the same system but in the absence of those hydrophobic parts of the polymer that are responsible for the interpolymer crosslinking. We use this approach to analyse new and previously published experimental data on a range of ionic and non-ionic hydrophobically modified polymers mixed with surfactants that form spherical micelles, but have widely different c.m.c.s. A consistent picture of the mixed micellar stoichiometries at the point of the maximum viscosity, and at the point of final dissolution of the mixed micellar crosslinks, emerges from this analysis.