J. Callejas-Fernández

Soft nanoparticles (thermo-responsive nanogels and bicelles) with biotechnological applications: from synthesis to simulation through colloidal characterization

The use of nanotechnology in biotechnological applications has attracted tremendous attention from researchers. Currently many nanomaterials, such as soft nanoparticles, are under investigation and development for their use in biomedicine. Among soft nanoparticles, polymeric gels in the nanometre range, known as nanogel particles, have received considerable attention. Nanogel particles, which are formed by polymeric chains loosely cross-linked to form a three-dimensional network, swell by a thermodynamically good solvent but do not dissolve in it. Nanogels are composed of hydrophilic polymers capable of undergoing reversible volume-phase transitions in response to environmental stimuli. Among them, temperature-sensitive nanogels showing a volume phase transition temperature (VPTT) near physiological temperature have been investigated in detail. Nanogels based on biocompatible and temperature-sensitive polymers having a lower critical solution temperature (LCST) around 32 °C in aqueous solutions swell at low temperatures and collapse at high ones. This unique behavior makes these nanogels attractive for pharmaceutical, therapeutical, and biomedical applications. In this review, different synthesis strategies to produce this type of nanogels in dispersed media are revised. Special attention is paid to poly(N-vinylcaprolactam) (PVCL)-based nanogels due to their proven biocompatibility. On the other hand, an extensive review on the characteristics, preparation, and physicochemical properties of another type of soft nanoparticles, which are the bicelles, is presented. The different morphologies obtained depending on experimental conditions such as temperature, lipid concentration, and long- and short-chain phospholipids molar ratio are revised, emphasizing on an important property of bicelles: their alignment in the presence of a magnetic field, and presenting the most important applications of bicelles as membrane models in diverse conformational studies of proteins and membrane peptides, together with the possibilities of administration of such vesicles by systemic routes. A key challenge for the characterization of both soft nanoparticles (nanogels and bicelles) involves the elucidation of their colloidal properties. In this work, some colloidal features of these nanoparticles such as their size, electric double layer or the internal structure and motions of their chains are analyzed. In addition, an overview on the previous and current understanding of the methods and techniques employed in this colloidal characterization is presented, mainly from an experimental point of view. Finally, the most recent results on polyelectrolyte gels and bicelles obtained from computer simulations are also briefly commented. Concerning polyelectrolyte gels, this review is mainly focused on the most important feature of these systems, their large capacity of swelling, which has been explored by simulation in the last decade.

Interaction potentials, structural ordering and effective charges in dispersions of charged colloidal particles.

As colloidal dispersions of charged particles exhibit a wide variety of commercial, technological and scientific applications, a considerable theoretical effort has been devoted to finding an effective interaction potential from primitive models. The forces derived from this potential should justify the spatial ordering experimentally observed under certain conditions. This paper reviews the advances in these theoretical studies as well as some experiments (based on the mentioned order) that try to corroborate them. Special attention has been paid to the Derjaguin-Landau-Verwey-Overbeek (DLVO) potential. Nowadays, many of these theoretical investigations suggest that it could be applied if some of its parameters are renormalized. Nevertheless, to achieve a renormalization procedure in a strict way (from a primitive model) is a difficult task as a result of the size and charge asymmetries between small ions and macroions. Thus, several procedures for computing renormalized charges in a simple way have been developed. However, the notion of effective charge has also been widely used (as a adjustable parameter) in order to justify results found for several kinds of colloids (like solid particle dispersions or micellar systems) by means of quite different experimental techniques. Renormalization (as well as ion condensation) approaches, experiments and the controversial relationship between theoretical and phenomenological effective charges are also reviewed in this work.

The aggregation behaviour of protein-coated particles: a light scattering study

The different mechanisms involved in the aggregation of spherical latex particles coated with bovine serum albumin (BSA) have been studied using static and dynamic light scattering. These techniques assess the fractal dimension of the aggregates and their mean hydrodynamic radius. Particles with different degrees of surface coverage have been prepared. The net charge of the covered particles has been modified by varying the pH of the aqueous phase. The aggregation rate was measured and used to determine the importance of the different aggregation mechanisms that are responsible for these types of flocculation processes. At low and intermediate degrees of surface coverage, bridging flocculation is the principal aggregation mechanism irrespective of the electrical state of the protein-particle complexes. At high degree of surface coverage, however, weak flocculation is important only when the BSA molecules are at their isoelectric point.

Effective electrostatic interactions arising in core-shell charged microgel suspensions with added salt

The mixture formed by charged (ionic) microgels in the presence of 1:1 added salt, with explicit consideration of a core-shell structure of the microgel particles, is studied. By solving numerically the three-component Ornstein-Zernike integral equations, the counter- and coion penetration inside the microgel network and the resulting effective microgel-microgel electrostatic interaction are calculated. This is done in the limit of very low microgel concentration, so that the resulting pair-wise effective potential is not affected by many-body particle-particle interactions. The ion-ion, microgel-ion, and microgel-microgel correlations are all treated within the Hypernetted-Chain approximation. The results obtained clearly show that the addition of salt to the microgel suspension has a deep impact on the screening of the bare charge of the particles, confirming an already well-known result: the strong reduction of the effective charge of the microgel occurring even for diluted electrolyte concentrations. We show that this effect becomes more important as we increase the shell size of the particle and derive a semi-empirical model for the effective charge as a function of the electrolyte concentration and the shell extension. The resulting microgel-microgel effective pair potential is analysed as a function of the shell extension and salt concentration. In all cases the interaction is a soft potential when particles overlap. For non-overlapping distances, our theoretical results indicate that microgel particles can be regarded as hard spherical colloids bearing an effective charge given by the net charge inside the particle and the microgel-microgel interaction shows a Yukawa-like behaviour as a function of the interparticle distance. It is also observed that increasing the bare-charge of the microgel induces a strong microgel-counterion coupling in the limit of very low electrolyte concentrations, which cannot be justified using linearized theories. This leads to an even more important adsorption of counterions inside the microgel network and to a reduction of the microgel-microgel effective repulsion.

Dynamic scaling concepts applied to numerical solutions of Smoluchowski's rate equation

Smoluchowski’s equation is widely applied to describe the time evolution of the cluster-size distribution during aggregation processes. Analytical solutions for this equation, however, are known only for a very limited number of kernels. Therefore, numerical methods have to be used for describing the time evolution of the cluster-size distribution. In this work, we present a novel self-consistent method for solving Smoluchowski’s equation for any homogeneous kernel. The method considers dynamic scaling to be valid but does not need to assume a given form for the scaling distribution Φ(x). Moreover, the scaling distribution Φ(x) is obtained as a natural result of the algorithm. Due to the implementation of dynamic scaling concepts, the algorithm converges almost immediately with a minimal calculation effort. Comparing calculated size distributions with the corresponding analytical solutions shows the validity of the method. The method is then used to fit experimental data for diffusion limited aggregation....

Effective charges of colloidal particles obtained from collective diffusion experiments

In this work, the collective diffusion coefficient of highly charged colloidal particles in dilute dispersions has been measured by means of dynamic light scattering. The possibility of obtaining valuable information about the particle charge from these data is looked into with the help of electrophoresis experiments. Our results suggest that this is possible in the case of slight or moderately interacting particles as long as experimental data are properly treated. For highly interacting colloids, however, such information could not be so reliable, presumably due to certain shortcomings of the experimental technique at low angle. The role of charge renormalization is also discussed in this work.

Structure of charged colloid-polymer mixtures

We use a light scattering technique to investigate the effect of adding non-adsorbing charged polymers to a very dilute electrostatically stabilized colloidal suspension at low electrolyte concentration. The experimental results show that, as the polymer concentration increases, the main peak of the colloid-colloid structure factor moves to higher q-values, which cannot be only due to the screening of the direct colloid-colloid electrostatic repulsion. We show that the colloid-polymer electrostatic repulsions lead to enhanced depletion forces that have a strong influence on the colloid structure, even for diluted suspensions. The experimental results are interpreted using the off-lattice Polymer Reference Interaction Site Model (PRISM), and very good agreement is found for all polymer concentrations.

Renormalization processes in the charge density of polymer colloids

Abstract The spatial microstructure exhibited by charge stabilized colloidal dispersion at very low ionic strength has been determined using static light scattering. The obtained structure factors have been analyzed assuming a DLVO type effective particle–particle interaction potential, and with the aid of the Ornstein–Zernike equation and the hyper-netted-chain closure. The effective charges needed to fit the experimental data in this way are found to be considerably smaller than the total number of ionizable groups on the surface. In order to account for this behavior, two approaches have been taken. Firstly, a widely used charge renormalization approach was applied. It is based on the idea that the potentials derived with linear approximations underestimate the actual charge characterizing the interaction. The surface charge does not seem to be an appropriate input parameter for this model. Secondly, electrophoretic mobilities were measured and converted into ζ-potential (using the O’Brien–White theory). The electrokinetic charges were also calculated. A discussion in terms of these electrokinetic data is presented. The similar behavior found between the effective and electrokinetic charges seems to point out that not only the renormalization has to be considered, but also the structure of the electric double layer.

Dynamic scaling and fractal structure of small colloidal clusters

Abstract We studied the aggregation of small colloidal polystyrene spheres during the limiting growth regime of diffusion-limited aggregation. The number-average mean cluster size and the fractal dimension of the aggregates were obtained by dynamic and static light scattering (DLS and SLS). The experimental results are interpreted using the spatial and dynamic scaling formalism. The homogeneity exponent λ was used to identify the aggregation mechanism. An unexpected cluster size scaling was observed for early aggregation stages. This feature allowed the use of spatial and dynamic scaling concepts as an alternative method for determining the Smoluchowski rate constant k 11 .

Simulated Reversible Aggregation Processes for Different Interparticle Potentials: The Cluster Aging Phenomenon

The kinetics of reversible 3D aggregation processes was studied for different interparticle potentials by means of simulations. In previous work ( Phys. ReV. E 2002, 65, 031405), 1 freely diffusing particles were considered that aggregate whenever a collision occurs but disintegrate only with a single given breakup probability. The DLVO theory, however, predicts also interparticle potentials showing two minima of different depths separated by an energetic barrier. Hence, two different kind of bonds, primary and secondary ones, can be formed and should be treated separately. In the present work, this behavior was implemented by considering bonds with different breakup probabilities. The data obtained from simulations were compared with the stochastic solutions of the corresponding master equation. For this purpose, the Brownian kernel was employed together with novel fragmentation kernels. The agreement between the simulations and the kinetic description was found to be quite satisfactory. Moreover, studying the time evolution of the bond population showed that cluster aging appears as a natural consequence of the employed model.