Approximate analytic expressions for the electrophoretic mobility of spherical soft particles.

Approximate analytic expressions are derived for the electrophoretic mobility of a weakly charged spherical soft particle consisting of the particle core covered with a surface layer of polymers in an electrolyte solution. The particle core and the surface polymer layer may be charged or uncharged. The obtained electrophoretic mobility expressions, which involve neither numerical integration nor exponential integrals, are found to be in excellent agreement with the exact numerical results. It is also found that the obtained mobility expressions reproduce all the previously derived limiting expressions and approximate analytic expressions for the electrophoretic mobility of a weakly charged spherical soft particle.

Use of Membrane Potential to Achieve Transmembrane Modification with an Artificial Receptor.

We developed a strategy to modify cell membranes with an artificial transmembrane receptor. Coulomb force on the receptor, caused by the membrane potential, was used to achieve membrane penetration. A hydrophobically modified cationic peptide was used as a membrane potential sensitive region that was connected to biotin through a transmembrane oligoethylene glycol (OEG) chain. This artificial receptor gradually disappeared from the cell membrane via penetration despite the presence of a hydrophilic OEG chain. However, when the receptor was bound to streptavidin (SA), it remained on the cell membrane because of the large and hydrophilic nature of SA.

Electrical phenomena of soft particles. A soft step function model.

Simple analytic expressions are derived for the electrophoretic mobility of a soft particle consisting of the hard particle core covered with an ion-penetrable surface layer of polyelectrolyte for the case where the electric potential is low. The effect of the distribution of the polymer segments is taken into account by modeling the surface layer as a soft step function with the inhomogeneous distribution width δ. It is shown that the electrophoretic mobility becomes lower than that for the hard step function model and that the maximum deviation of the soft step function model from the hard step function model, which is a function of λδ (where 1/λ is the softness parameter) and κ/λ (where κ is the Debye-Hückel parameter), is 2.7% at λδ = 0.1, 5.1% at λδ = 0.2, and 11% at λδ = 0.5. In the limit of very high electrolyte concentrations, the obtained mobility expression tends to the result derived from the conventional hard step function model. In addition, an analytic expression for the interaction energy between two similar soft plates is derived on the basis of the present soft step function model. The magnitude of the interaction energy is shown to decrease by a factor 1/(1 + κδ)(2). Approximate analytic expressions for the interaction energies between two similar soft spheres and between two similar soft cylinders are also derived with the help of Derjaguin's approximation.

Effective viscosity of a concentrated suspension of uncharged spherical soft particles.

We present a theory of the effective viscosity eta(s) of a concentrated suspension of uncharged polymer-coated spherical particles, which are termed uncharged spherical soft particles, in a liquid of viscosity eta on the basis of a cell model. These particles consist of the uncharged particle core of radius a covered with an uncharged polymer layer of thickness d (a polymer-coated particle thus has an inner radius a and an outer radius b = a + d). We assume that polymer segments are regarded as resistance centers, exerting frictional forces--gamma u on the liquid flowing in the polymer layer, where u is the liquid velocity and gamma is the frictional coefficient. We derive an analytic expression for the effective viscosity eta(s) of the suspension, which depends on the radii a and b, and volume fraction phi of the spheres and a parameter lambda = (gamma/eta)(1/2). The obtained expression for eta(s) exhibits the correct limiting behaviors. That is, as phi --> 0, the obtained expression for eta(s) becomes that for a dilute suspension of uncharged soft spheres (Ohshima, Langmuir 2008, 24, 6453). As a --> 0, the obtained viscosity expression becomes that for the case of a concentrated suspension of uncharged porous spheres (Ohshima, Colloids Surf. A: Physicochem. Eng. Aspects 2009, 347, 33). In the further limit of a --> 0 and phi --> 0, the obtained viscosity expression becomes the viscosity expression derived for the case of a dilute suspension of uncharged porous spheres by Natraj and Chen (J. Colloid Interface Sci. 2002, 251, 200). As lambda --> infinity or a --> b, the obtained viscosity expression tends to Simha's result (J. Appl. Phys. 1952, 23, 1020) for a concentrated suspension of uncharged rigid spheres of radius b, while as lambda --> 0, it becomes that for uncharged rigid spheres of radius a.

Effect of geometrical structure on the biodegradation of a three-dimensionally perforated porous apatite/collagen composite bone cell scaffold.

A Biodegradable artificial bone with inter-connective pores was prepared using a self-setting apatite/collagen composite cement as a cell scaffold for bone regenerative medicine, and investigated as to biocompatibility by X-ray computed tomography (CT) after its implantation into rats. Blocks (APN, APC and ACC) of apatite cement, apatite cement with continuous holes, and apatite/collagen composite cement with continuous holes were prepared. The APC and ACC blocks had 16 (8x2) interconnecting holes 500 microm in diameter. After the APN, APC, and ACC blocks were implanted in the back of the rats, X-ray CT images were measured every week. Before and after implantation, powder X-ray diffraction profiles of APN, APC and ACC showed diffraction patterns of hydroxyapatite with low crystallinity. Changes in the volume, inorganic content and density of the blocks in the rats were evaluated based on X-ray CT images. The volume and inorganic content of ACC decreased continuously at a constant rate. In contrast, the volume and inorganic content of APN and APC didn't show major changes. After implantation, the absorption of X-rays by ACC decreased with time. This suggested that the block was bioabsorbed significantly with time. In contrast, the absorption of APC and APN did not decrease, indicating that the blocks were not bioabsorbed.

The Donnan potential-surface potential relationship for a cylindrical soft particle in an electrolyte solution.

Transcendental equations, which avoid integration of the nonlinear Poisson-Boltzmann equations, are presented for obtaining the relationship between the Donnan potential and surface potential of a cylindrical soft particle (i.e., a polyelectrolyte-coated cylindrical particle) in a symmetrical electrolyte solution. Numerical results obtained by the present method are in excellent agreement with exact results obtained by solving the nonlinear cylindrical Poisson-Boltzmann equations both inside and outside the polyelectrolyte layer.

Push-Pull Controlled Drug Release Systems: Effect of Molecular Weight of Polyethylene Oxide on Drug Release.

First, an elementary osmotic pump (EOP) with a simple structure was prepared using polyethylene oxide (PEO) and NaCl as an excipient, and the influence of the molecular weight (Mw) of PEO on drug release was investigated. In the dissolution test of EOP, it was observed that the gelated core tablet was pushed out through the orifice. The dissolution profile of EOP was sigmoidal, and despite the short time, a zero-order release region was observed. The gel swelling rate in the zero-order region was independent of the Mw of PEO. It was also found that higher the Mw of PEO, the larger the saturated swelling amount. Next, a push-pull pump (PPP) with almost identical formulation to that of EOP was prepared, and its drug release characteristics were investigated. PPPs were prepared by varying the combination of Mws of PEO in both layers, and their dissolution profiles were compared. It was found that PPP using a low-Mw PEO for the drug layer and PEO with a high-Mw in the push layer showed the longest dissolution profile of the linear region. The obtained findings suggested that the properties of PEO and its hydrogel play a crucial role in the drug release of PPP.

Colloidal stability of aqueous polymeric dispersions: effect of pH and salt concentration.

Aqueous film coatings often contain some electrolytes, organic acids, and pigments to give functions of sustained release, time-controlled release, or protection against light. Additions of some electrolytes or organic acids into latex dispersion for an aqueous film coating affect its colloidal stability. We characterized the aqueous polymeric latexes used in the pharmaceutical industry by measuring zeta potential and particle size, and evaluated this colloidal stability using DLVO theory. Three polymethacrylate-based aqueous polymeric latexes, Eudragit L30D-55, Eudragit RS30D and Eudragit NE30D, having anionic, cationic, and neutral polymer, respectively, were used in this study. The Hamaker constant of the polymethacrylate-based latex was determined to be 6.35 x 10(-21) J, and the total potential energy of the latex dispersion was calculated. The total potential energy of interaction between pairs of latex particles changes by altering the salt concentration and pH. The experimental results of stability in the anionic and the cationic latex dispersions can be explained by the total interaction energies. However, the stabilization of the neutral latex did not match the calculated result. The steric interaction produced by the surfactant likely resulted in the stable dispersion of this latex.

Characterization of latex particles for aqueous polymeric coating by electroacoustic method.

Concentrated dispersions are used as coating dispersions for aqueous polymeric coatings, and characterization of the actual concentrated dispersions is an important in the pharmaceutical industry. The commonly used aqueous coating polymers are acrylic polymers and cellulose derivatives. We conducted a characterization study of polymethacrylate-based aqueous polymeric latex for aqueous coating, Eudragit L30D-55 (A-latex) and Eudragit RL30D (C-latex), by electroacoustic method. Colloidal Vibration Current (CVI) is one of the most important parameters relating to dynamic electrophoretic mobility and zeta potential, so we evaluated this parameter first. Volume fractions var of the latex in concentrated dispersions affect the CVIs according to the theory of Dukhin et al. The A-latex and C-latex CVI(*)s which were corrected with regard to the effect of volume fraction by the theoretical equation were nearly constant independent of phi in the ranges >0.04 and >0.03, respectively. The zeta potentials and colloidal stabilities of the concentrated dispersions were evaluated using an electroacoustic method by altering the pH and salt concentration. A-latex strongly aggregated at and below pH 2.5 and at and beyond 0.06 mol/L of electrolyte concentration. Regarding C-latex, instable dispersion was observed at 0.3 and 1 mol/L of NaCl concentration. The total potential energy of interaction between pairs of latex particles was changed by altering the salt concentration in this dispersion based on DLVO theory. The experimental results of stability in the concentrated latex dispersions can be explained by the total interaction energies.

Colloidal stability of aqueous polymeric dispersions: effect of water insoluble excipients.

An important issue in the aqueous coating process is dispersion stability. An unstable dispersion results in aggregation of the colloidal particles, thereby affecting the film coating process. In the coating suspension containing pigment, a latex for aqueous film coating might interact with pigment, resulting in unstable dispersion. We therefore conducted a stability investigation in a mixed dispersion including latexes, EudragitL30D-55 (A-latex), EudragitRL30D (C-latex) and EudragitNE30D (N-latex) and pigments, titanium dioxide and iron oxide yellow. An aggregation of the dispersion containing A-latex was observed at pH 2. Regarding the dispersions with C-latex and N-latex, no aggregation was observed in the range pH 2-11. We calculated total interaction energy between latex-latex particles, pigment-pigment particles and latex-pigment particles based on DLVO theory. The calculated results explained two mechanisms of the stable mixed dispersion. The first was that the individual latex particle and the pigment particle dispersed without aggregation in the mixed dispersion because of the electrostatic interaction. The next was that the latexes adsorbed onto the surface of the pigments, making electrostatically stable heterocoaggregates. We also calculated the binding constant of iron oxide yellow for C-latex at pH 10. The value of the constant was determined to be 1.1 x 10(-2).

A theory of overshoot phenomena in an ion-exchange membrane system.

A simple theory based on a kinetics equation with time delay is presented for ion permeation through an ion-exchange membrane for the case where two or more species of ions of the same charge are permeating from solutions 1 to 2 through the membrane. This theory explains the observation of Neihof and Sollner that if the exchange rates of ionic species are quite different from each other, then the concentration of the fastest exchanging species of ions in solution 2 exhibits overshoot [R. Neihof, K. Sollner, J. Phys. Chem. 61 (1957) 159].

Overshoot and oscillation in surface tension of gelatin solutions.

The experimental data of the surface tension of aqueous gelatin solution reported by Sato and Ueberreiter [H. Sato, K. Ueberreiter, Macromol. Chem. 180 (1979) 829; H. Sato, K. Ueberreiter, Macromol. Chem. 180 (1979) 1107; H. Sato, K. Ueberreiter, ACS Polym. Preprints 20 (1979) 907] were analyzed with a theory of adsorption kinetics with time delay. It is found that the observed overshoot and oscillation of the surface tension are well explained by the present theory. The delay time and the rate constants of adsorption and desorption of gelatin molecules onto the air/gelatin solution interface have been evaluated.

Therapeutic effect of in vivo sustained estradiol release from poly (lactide-co-glycolide) microspheres on bone mineral density of osteoporosis rats.

Poly (lactide-co-glycolide or PLGA) microspheres containing 0.3% (w/w) of estradiol were prepared by a solvent evaporation method. These PLGA microspheres had a wide particle distribution between 0.5 and more than 100 microm. The average size was 76 microm. Physicochemical properties of the microspheres were characterized by X-ray diffraction patterns, FT-IR spectra and DSC. In vitro estradiol release was maintained at a constant rate from these PLGA microspheres for 1 month. The loaded drug was totally recovered in the collection buffer within this time period. In vivo experiments were performed on Wistar rats that had received ovariectomy. These rats were fed with a vitamin D-deficient and Ca-deficient diet. The combination of ovariectomy and diet induced osteoporosis. PLGA microspheres containing either 50, 100, or 200 microg estradiol were injected into these rats. The plasma estradiol in each rat was monitored for 50 days. These in vivo drug release patterns were found to be different from the one obtained from in vitro release. The Ca-AUC was not significant different among various dosages administered. However, bone mineral density for rats after the injection of estradiol loaded microspheres was higher than that obtained for the control. This suggested that all estradiol microspheres administration induced bone generation in osteoporosis rats.

Double-phase-functionalized magnetic Janus polymer microparticles containing TiO2 and Fe2O3 nanoparticles encapsulated in mussel-inspired amphiphilic polymers.

Recently, anisotropic colloidal polymeric materials including Janus microparticles, which have two distinct aspects on their surfaces or interiors, have garnered much interest due to their anisotropic alignment and rotational orientation with respect to external electric or magnetic fields. Janus microparticles are also good candidates for pigments in "twisting ball type" electronic paper, which is considered promising for next-generation flexible display devices. We demonstrate here a universal strategy to encapsulate inorganic nanoparticles and to introduce different such inorganic nanoparticles into distinct polymer phases in Janus microparticles. TiO2 and Fe2O3 nanoparticles were separately encapsulated in two different mussel-inspired amphiphilic copolymers, and then organic-inorganic composite Janus microparticles were prepared by simple evaporation of solvent from the dispersion containing the polymer and nanoparticle. These Janus microparticles were observed to rotate quickly in response to applied magnetic fields.

Dissolution medium responsive simvastatin release from biodegradable apatite cements and the therapeutic effect in osteoporosis rats.

Bio-convertible artificial bone with slow release of anti-osteoporosis drug is useful to treat osteoporosis. Apatite cement containing 6% simvastatin (APD) had lower crystallinity than natural bone. In-vitro drug release tests in simulated body fluid (pH 7.8) and acetate buffer (pH 4.5) were performed at 37.0 C as physical models of osteoblast and osteoclast conditions (SOB and SOC). The device had lower drug release rate under SOB, but significantly higher rates under SOC. The simvastatin release rate changed depending on dissolution media, it repeated twice, and the rate under SOC was 15 times higher than under SOB. The device showed dissolution medium responsive drug release. After implantation of the APD in osteoporosis rats, the bone mineral density was evaluated by the x-ray computed tomography. The result indicated that the bone mineral density of APD implanted rat was significantly higher than that of control diseased. The result indicated that the device was therapeutically useful to bone regeneration.

Determination of effective charge of small ions, polyelectrolytes and nanoparticles by capillary electrophoresis.

In this paper, a systematic and comparative study related to the effective charge determination of three kinds of solutes (small ions, polyelectrolytes and nanoparticles) was performed. Four approaches were compared regarding their conditions of validity and their advantages/disadvantages. Three of them allow the effective charge determination from the electrophoretic mobility and the hydrodynamic radius of the solutes using electrophoretic mobility modelings based on Nernst-Einstein (NE), O'Brien-White-Ohshima (OWO) and Yoon and Kim (YK) equations. Electrophoretic mobility and hydrodynamic radius were determined by capillary electrophoresis and Taylor dispersion analysis, respectively, using the same instrumentation in similar conditions, on a large set of samples. A fourth experimental approach based on the sensitivity of detection in indirect UV detection mode (IUV) was compared to the previously mentioned methods. OWO and YK modelings are well adapted for the effective charge determination of small ions and nanoparticles, while IUV is the only method adapted for polyelectrolytes.

Electrostatic interaction between two cylindrical soft particles.

An expression for the potential energy of electrostatic interaction between two soft cylinders (i.e., polyelectrolyte-coated cylindrical particles) in an electrolyte solution is derived by applying Derjaguin's approximation to the corresponding interaction energy between two parallel soft plates for the case where the density of fixed charges within the polyelectrolyte layer is low. The interaction between two parallel cylinders and that between two crossed cylinders are considered. The obtained expression covers various limiting cases that include hard cylinder/hard cylinder interaction, cylindrical polyelectrolyte/cylindrical polyelectrolyte interaction, soft cylinder/cylindrical polyelectrolyte interaction, soft cylinder/hard cylinder interaction, and cylindrical polyelectrolyte/hard cylinder interaction.

Electrostatic interaction between soft particles.

Electrostatic interaction between two soft particles (i.e., polyelectrolyte-coated particles) in an electrolyte solution is discussed. An approximate analytic expression for the interaction energy between two dissimilar soft spheres is derived by applying Derjaguin's approximation to the corresponding interaction energy between two parallel dissimilar soft plates for the case where the density of fixed charges within the polyelectrolyte layer is low. The obtained expression covers various limiting cases that include hard sphere/hard sphere interaction, spherical polyelectrolyte/spherical polyelectrolyte interaction, soft sphere/spherical polyelectrolyte interaction, soft sphere/hard sphere interaction, and spherical polyelectrolyte/hard sphere interaction.

Electrophoresis of diffuse soft particles.

A theory is presented for the electrophoresis of diffuse soft particles in a steady dc electric field. The particles investigated consist of an uncharged impenetrable core and a charged diffuse polyelectrolytic shell, which is to some extent permeable to ions and solvent molecules. The diffuse character of the shell is defined by a gradual distribution of the density of polymer segments in the interspatial region separating the core from the bulk electrolyte solution. The hydrodynamic impact of the polymer chains on the electrophoretic motion of the particle is accounted for by a distribution of Stokes resistance centers. The numerical treatment of the electrostatics includes the possibility of partial dissociation of the hydrodynamically immobile ionogenic groups distributed throughout the shell as well as specific interaction between those sites with ions from the background electrolyte other than charge-determining ions. Electrophoretic mobilities are computed on the basis of an original numerical scheme allowing rigorous evaluation of the governing transport and electrostatic equations derived following the strategy reported by Ohshima, albeit within the restricted context of a discontinuous chain distribution. Attention is particularly paid to the influence of the type of distribution adopted on the electrophoretic mobility of the particle as a function of its size, charge, degree of permeability, and solution composition. The results are systematically compared with those obtained with a discontinuous representation of the interface. The theory constitutes a basis for interpreting electrophoretic mobilities of heterogeneous systems such as environmental or biological colloids or swollen/deswollen microgel particles.

Modified Henry function for the electrophoretic mobility of a charged spherical colloidal particle covered with an ion-penetrable uncharged polymer layer.

An approximate expression is derived for the electrophoretic mobility of a spherical charged colloidal particle carrying low zeta potential covered with an ion-penetrable uncharged polymer layer in an electrolyte solution. This expression, which becomes Henry's mobility formula in the absence of the polymer layer, is a modification of Henry's mobility formula by taking into account the presence of the uncharged polymer layer.