Magnetic properties of γ-Fe2O3 nanoparticles in a porous SiO2 shell for drug delivery.

A method is presented for synthesizing core-shell nanoparticles with a magnetic core and a porous shell suitable for drug delivery and other medical applications. The core contains multiple γ-Fe2O3 nanoparticles (∼15 nm) enclosed in a SiO2 (∼100-200 nm) matrix using either methyl (denoted TMOS-γ-Fe2O3) or ethyl (TEOS-γ-Fe2O3) template groups. Low-temperature Mössbauer spectroscopy showed that the magnetic nanoparticles have the maghemite structure, γ-Fe2O3, with all the vacancies in the octahedral sites. Saturation magnetization measurements revealed that the density of γ-Fe2O3 was greater in the TMOS-γ-Fe2O3 nanoparticles than TEOS-γ-Fe2O3 nanoparticles, presumably because of the smaller methyl group. Magnetization measurements showed that the blocking temperature is around room temperature for the TMOS-γ-Fe2O3 and around 250 K for the TEOS-γ-Fe2O3. Three dimensional topography analysis shows clearly that the magnetic nanoparticles are not only at the surface but have penetrated deep in the silica to form the core-shell structure.

Cell toxicity of superparamagnetic iron oxide nanoparticles.

The performance of nanoparticles for biomedical applications is often assessed by their narrow size distribution, suitable magnetic saturation and low toxicity effects. In this work, superparamagnetic iron oxide nanoparticles (SPIONs) with different size, shape and saturation magnetization levels were synthesized via a co-precipitation technique using ferrous salts with a Fe(3+)/Fe(2+) mole ratio equal to 2. A parametric study is conducted, based on a uniform design-of-experiments methodology and a critical polymer/iron mass ratio (r-ratio) for obtaining SPION with narrow size distribution, suitable magnetic saturation, and optimum biocompatibility is identified. Polyvinyl alcohol (PVA) has been used as the nanoparticle coating material, owing to its low toxicity. A 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay is used to investigate the cell biocompatibility/toxicity effects of the samples. From the MTT assay results, it is observed that the biocompatibility of the nanoparticles, based on cell viabilities, can be enhanced by increasing the r-ratio, regardless of the stirring rate. This effect is mainly due to the growth of the particle hydrodynamic size, causing lower cell toxicity effects.

Phosphatidylserine/Cholesterol Bilayers Supported on a Polycation/Alkylthiol Layer Pair.

1-Stearoyl-2-oleoyl phosphatidylserine (SOPS)/cholesterol bilayers, supported on a polycation/alkylthiol layer pair on a gold surface, were investigated by surface plasmon resonance (SPR) and fluorescence recovery after photobleaching. The substrate was formed by electrostatic adsorbance of a hydrated poly(diallyldimethylammonium chloride) (PDDA) layer on the negatively charged surface of a self-assembled monolayer of 11-mercaptoundecanoic acid (MUA) on gold. Lipid membranes with different SOPS/cholesterol compositions were deposited on the PDDA/MUA layer pair by vesicle fusion. When the cholesterol content was below 20%, single bilayers were deposited. Fluorescence recovery after the bleaching experiments revealed that the SOPS/cholesterol bilayers were mobile at room temperature; lateral diffusion coefficients of a fluorescence probe were approximately 1x10(-9) cm(2)/s. The kinetics of the addition of the ion-channel-forming peptide gramicidin to the supported bilayers was detected by SPR. Copyright 2000 Academic Press.

Studies on the Diffusion of Molecules through Pores in Monolayer and Multilayer Films.

A one-parameter model for species flux through pores in a crystalline monolayer or multilayer film is developed. The model is based on surface diffusion of the species on the upstream surface of the monolayer and one-directional diffusion of the species into the pores of the monolayer. It is found that the Fickian diffusivity depends on the concentration of adsorbed species on surface sites and on the pore coverage. The model contains an important parameter, the rate constant of activation, which is function of the diffusing species and film surface properties. The model is compared with experimental data on ion and gas flux through single and multilayer films. Good agreement between theory and experiment is found with all sets of the data with the rate constant as a sole adjustable parameter. Copyright 1998 Academic Press.

Imaging of hard- and soft-tissue structure in the oral cavity by optical coherence tomography.

We have developed a prototype optical coherence tomography (OCT) system for the imaging of hard and soft tissue in the oral cavity. High-resolution images of in vitro porcine periodontal tissues have been obtained with this system. The images clearly show the enamel-cementum and the gingiva-tooth interfaces, indicating OCT is a potentially useful technique for diagnosis of periodontal diseases. To our knowledge, this is the first application of OCT for imaging biologic hard tissue.

Dental OCT.

We present here the first in vivo optical coherence tomography (OCT) images of human dental tissue. A novel dental optical coherence tomography system has been developed. This system incorporates the interferometer sample arm and transverse scanning optics into a handpiece that can be used intraorally to image human dental tissues. The average imaging depth of this system varied from 3 mm in hard tissues to 1.5 mm in soft tissues. We discuss the application of this imaging system for dentistry and illustrate the potential of our dental OCT system for diagnosis of periodontal disease, detection of caries, and evaluation of dental restorations.

Determination of cell membrane permeability in concentrated cell ensembles.

The method of volume averaging is used to analyze the process of diffusion in concentrated cell ensembles in which significant resistance to mass transfer is caused by the cellular membrane. A general closure scheme is given that allows for direct theoretical prediction of effective diffusivities for any cellular geometry. Numerical results are presented for the classical parallelepiped arrangement used to model cellular systems, and these results are used in conjunction with experimental studies of concentrated cell ensembles to determine membrane permeabilities for solute diffusion in several cellular systems. Membrane permeabilities are compared with predictions from other models of diffusion in cellular systems.

Nonequilibrium facilitated transport of carbon dioxide in bicarbonate and bovine albumin solutions.

The nonlinear diffusion-reaction equations describing the nonequilibrium transport of CO2 through flat layers of complex but homogeneous aqueous media were solved by an approximate analytical method called the "Combined Damköhler Number" (CDN) technique. Unlike other approximate analytical solutions, the CDN technique is valid for the full range of Damköhler numbers, i.e., for any layer thickness. The present theoretical treatment uses as a basis the equilibrium approach of Stroeve, Hoofd, and Kreuzer which accounts for any species in the solution except for possible carbamate formation (binding of CO2 by the protein). The nonequilibrium model developed here for CO2 transport is the most general technique currently available in the literature. Theoretical results were compared to experimental data from the literature for diffusion in bicarbonate and albumin solutions and were generally in good agreement. Results obtained from numerical calculations were also compared and were found to be in excellent agreement with the CDN results.

Facilitated carbon dioxide transport in bovine albumin solutions.

Steady-state CO2 diffusion in the presence of a CO2 gradient was measured in thin layers of bovine albumin solutions containing different amounts of buffer base, added as NaHCO3, and/or of NaCl. In the same solutions, electrical potentials due to the CO2 diffusion across the layers were measured. Addition of carbonic anhydrase induced a chemical reaction equilibrium to exist for the CO2 reaction system, and led to equilibrium values for facilitated CO2 transport due to a bicarbonate flux and to maximum values for the diffusion potential. The diffusion potentials are generated due to the large differences in the ionic mobilities of albumin and other ionic species such as bicarbonate. The diffusion potential markedly reduces the facilitated CO2 flux. The presence of sodium chloride had no significant effect on the CO2 transport rate. The total mass transfer rates of CO2 in albumin solutions were considerably lower than those found by Stroeve and Ziegler (23) in hemoglobin solutions at identical concentrations of buffer base.

Lateral diffusion of cholesterol in monolayers.

The surface diffusion coefficient of cholesterol in cholesterol monolayers has been measured as a function of cholesterol surface concentration. Two different radiochemical methods, one integral and the other differential, were developed which gave comparable results. In the integral method two cholesterol monolayers, one of which is radioactive, are isolated on inert hydrophilic supports and then brought into contact. After some time the supports are separated and the radioactivity of the supports is measured. The differential method is an autoradiographic experiment. Two cholesterol monolayers, one of which is radioactive, are separated by means of a thin barrier. Upon removal of the barrier and at later times, an autoradiographic plate is brought to within a fraction of a mm from the aqueous surface and exposed. The plates are developed and analysed. The data show that the cholesterol surface diffusion coefficient in the dilute monolayers is approximately 10(-6)cm2/s and is nearly independent of surface concentration up to a concentration corresponding to an area of 40 A2/molecule. As the monolayer becomes compressed beyond this surface concentration, the diffusion coefficient decreases ubruptly with the deeply decreasing surface tension to about 10(-7) cm2/s, when a fully condensed surface layer of 38 A2/molecule is reached. This diffusion coefficient is of the same order of magnitude as the diffusion coefficients measured in lipid bilayers and in membranes.