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## Publications

Publications (58)

To measure progress and evaluate performance of the newest UB/UC/P&G skin penetration model we simulated an 18-compound subset of finite dose in vitro human skin permeation data taken from a solvent-deposition study of cosmetic-relevant compounds (Hewitt et al., J. Appl. Toxicol. 2019, 1-13). The recent model extension involved slowly reversible bi...

Interpretation of experiments involving transient solute binding to isolated keratin substrates is analyzed and discussed in terms of their impact on transient permeation of topically-applied compounds through human stratum corneum. The analysis builds upon an earlier model (Nitsche and Frasch 2011 Chem Eng Sci 66:2019-41) by adding a second level...

This paper develops a detailed model of human and bovine erythrocytes quantifying the dependence of total cell volume upon composition of an aqueous solution in which it is immersed. The cytoplasm is represented as an aqueous solution of hemoglobin and salt (KCl or NaCl). Model-based analysis of literature data on human erythrocytes, and of new exp...

Owing to the systematic alignment and ordering of fatty acid and/or ceramide chains, lipid layers in biological membranes have strongly anisotropic diffusion properties. The diffusivity D||lip for solute transport in the direction parallel to the lipid layer is typically 103-105 times the diffusivity D⊥lip for the perpendicular direction. This pape...

Partition coefficients between human stratum corneum lipids and water (K(sclip/w)) are collected or deduced from a variety of sources in a manner that approximately doubles the available data compared to the current state-of-the-art model [Hansen et al., Adv Drug Deliv Rev 65:252-264 (2013)]. An additional datum for water itself in porcine SC that...

The permeability of gel-phase phospholipids is typically about an order of magnitude lower than that of the same compositions in the fluid phase, yet a quantitative description of the ordering factors leading to this difference has been elusive. The present analysis examines these factors with particular focus on the area per phospholipid chain, Ac...

Permeability data (P(lip/w) ) for liquid crystalline phospholipid bilayers composed of egg lecithin and dimyristoylphosphatidylcholine (DMPC) are analyzed in terms of a mathematical model that accounts for free surface area and chain-ordering effects in the bilayer as well as size and lipophilicity of the permeating species. Free surface area and c...

A microscopic model of passive transverse mass transport of small solutes in the viable epidermal layer of human skin is formulated on the basis of a hexagonal array of cells (i.e., keratinocytes) bounded by 4-nm-thick, anisotropic lipid bilayers and separated by 1-μm layers of extracellular fluid. Gap junctions and tight junctions with adjustable...

This letter critiques a new correlation for deca-1,9-diene/water partition coefficients reported by Abraham and Acree. Solvation parameters used as independent variables should represent fundamental molecular properties, yet they are assigned revised values apparently based partly on the very data being fitted. The result is a self-fulfilling proph...

An important series of papers by Xiang, Anderson, and coworkers has established the strong correlation between phospholipid bilayer membrane permeability and the 1,9-decadiene/water partition coefficient over a wide range of compounds, elevating the importance of K(decadiene/w) as a predictor of molecular bioavailability. On the basis of a 58-point...

A computational model for estimating dermal clearance in humans of arbitrary, nonmetabolized solutes is presented. The blood capillary component employs slit theory with contributions from both small (10 nm) and large (50 nm) slits. The lymphatic component is derived from previously reported clearance measurements of dermal and subcutaneous injecti...

New data sets on both (i) equilibrium theophylline (TH) partitioning/binding in stratum corneum and (ii) transient TH diffusion through human epidermis are explained by an extended partition-diffusion model with reversible binding. Data conform to a linear binding isotherm within the tested concentration range (0-2000 μg/mL) with an equilibrium rat...

DNA microarrays have the potential to revolutionize medical diagnostics and development of individualized medical treatments. However, accurate quantification of scantily expressed genes and precise measurement of small differences between different treatments is not currently feasible. A major challenge remains the understanding of physicochemical...

The full parameterization for the stratum corneum biphasic microtransport model presented previously in this Journal [95:620-648 (2006)] is developed through a combination of fundamental transport theory and calibration with existing data. Of the five microscopic transport properties, four (D(cor), K(cor/w), D(lip), K(lip/w)) are developed from sou...

Absorption of molecules (applied drugs and chemicals) through the skin proceeds by sequential diffusion steps through the stratum corneum (SC, barrier), viable epidermal, and dermal layers (1-3). Within each of these strata, absorption involves partitioning into and diffusion within several components of an inherently heterogeneous microstructure,...

A two-dimensional microscopic transport model of the stratum corneum (SC) incorporating corneocytes of varying hydration and permeability embedded in an anisotropic lipid matrix is presented. Results are expressed in terms of a dimensionless permeability (P(SC/w)(comp), which is a function of two dimensionless parameters, R and sigma. R is a ratio...

An analysis is presented of partition coefficients K(SC/w) describing solute distribution into fully hydrated stratum corneum (SC) from dilute aqueous solution (w). A comprehensive database is compiled from the experimental literature covering more than eight decades in the octanol/water partition coefficient K(o/w). It is analyzed according to a t...

This paper addresses the manner in which drugs and chemicals applied to skin penetrate into dermal tissue around hair follicles. Aside from follicular drug delivery per se, quantitative modeling of this process is important to topical and transdermal drug delivery generally, as well as risk assessment of chemical exposure, because hair follicles an...

Quantitative predictions of molecular transport rates through the skin are key to the development of topically applied and transdermally delivered drugs, as well as risk assessment associated with dermal exposure. Most research to date has focused on correlations for the permeability of the stratum corneum, and transient diffusion models that overs...

Gap junctions have traditionally been characterized as nonspecific pores between cells passing molecules up to 1 kDa in molecular mass. Nonetheless, it has become increasingly evident that different members of the connexin (Cx) family mediate quite distinct physiological processes and are often not interchangeable. Consistent with this observation,...

As ubiquitous conduits for intercellular transport and communication, gap junctional pores have been the subject of numerous investigations aimed at elucidating the molecular mechanisms underlying permeability and selectivity. Dye transfer studies provide a broadly useful means of detecting coupling and assessing these properties. However, given ev...

At low water activities, stratum corneum (SC) water sorption resembles that in other keratinized tissues (i.e., wool and horn), whereas at high water activities, it resembles that in polymeric hydrogels. We propose that the concentration-dependent water diffusivity observed in these other systems applies to the corneocyte phase of the SC. An increa...

The transport and kinetic processes describing biomolecular interactions in the BIACORE optical biosensor have been studied with the help of a mathematical model. In comparison to previous models, the model presented here couples, for the first time, transport phenomena in the flow channel with hindered diffusive transport and reactions inside the...

The functional diversity of gap junction intercellular channels arising from the large number of connexin isoforms is significantly increased by heterotypic interactions between members of this family. This is particularly evident in the rectifying behavior of Cx26/Cx32 heterotypic channels (. Proc. Natl. Acad. Sci. USA. 88:8410-8414). The channel...

Surface plasmon resonance based biosensors have become
increasingly popular for the measurement of the kinetic constants in a
wide variety of biomolecular interactions. One of the most popular
biosensors based on this principle is the BIACORE instrument. A
mathematical model is presented describing biomolecular interactions in
the flowcell of the B...

Ionic and molecular transfer among cells occurs by a variety of transport processes operative at different length scales. Cell membrane permeability and electrical conductance derive from channel proteins producing pores at the molecular (ultrastructural) scale. Intracellular mobility involves the dynamics of motion through the complex ultrastructu...

Gap junctions provide direct intercellular communication by linking adjacent cells with aqueous pores permeable to molecules up to 1 kDa in molecular mass and 8-14 A in diameter. The identification of over a dozen connexins in the mammalian gap junction family has stimulated interest in the functional significance of this diversity, including the p...

This paper presents a theoretical and experimental exploration of the prospects for performing separations on size- or shape-polydispersed solutions of macromolecules or colloidal particles via multistage countercurrent contact between liquid and porous phases. Fractional extraction is shown to yield an arbitrarily sharp cut with sufficiently many...

The general purpose of this paper is to investigate some consequences
of the randomness of the velocities of interacting rigid particles falling
under
gravity through viscous
fluid at small Reynolds number. Random velocities often imply diffusive
transport
of the particles, but particle diffusion of the conventional kind exists
only
when t...

We investigate convective-diffusive transport of a solute through a medium with properties that can be externally modulated
in space and time. In particular, we focus on the effect of a front—a sharp transition in the convective velocity (v) and diffusivity (D)—on the evolution of the solute concentration profile. Numerical results show that by sui...

Electrophoresis of a solute through a column in which its transport is governed by the convection – diffusion equation is described. Approximate solutions to the convection – diffusion equation in the limit of small diffusion are developed using perturbation methods. The diffusion coefficient and velocity are assumed to be functions of space and ti...

Motivated by applications to electrophoretic techniques for bioseparations, we consider transient one-dimensional convection-diffusion through a medium in which the solute diffusivity and convective velocity undergo step changes at a prescribed position. An exact method of solution of the governing transport equations is formulated in terms of a la...

A theoretical investigation is presented of the convection-diffusion of model nonspherical solutes in shear flow over a plane wall. The analysis proceeds by formulating the underlying configuration-space Brownian transport equation for the distribution over accessible positions and orientations. Geometrical constraints are imposed via boundary cond...

A general asymptotic theory is presented for approximating the electrostatic free energy of interaction between a charged spherical solute of radius a and an arbitrarily shaped charged wall at distance in the limit a . The Debye screening length is assumed to be of order or larger. Thus, the analysis specifically addresses the most interesting cas...

An analysis is presented of the steady-state diffusion of spherical Brownian partcles through an effectively infinite expanse of fluid perforated by a circular cylindrical fiber. Detailed Stokes-flow calculations quantify the solute-fiber hydrodynamic interaction in three regimes covering the full range of solute-fiber separations, and lead to an a...

A general theory is presented for calculating the effective diffusivity (D) over bar of an arbitrarily shaped Brownian solute diffusing within a straight pore of arbitrary cross section. Hydrodynamic interactions with the walls as well as rotational diffusion of the solute are rigorously accounted for. Asymptotic analysis leads to the conclusion th...

A detailed model is presented for protein binding to active surfaces, with application to the binding of avidin molecules to a biotin-functionalized fiber optic sensor in experiments reported by S. Zhao and W. M. Reichert (American Chemical Society Symposium Series 493, 1992). Kinetic data for binding in solution are used to assign an intrinsic cat...

A detailed analysis is presented of the translational and rotational transport processes underlying site-specific binding of a diffusing solute with a fixed target molecule. The need for contact to occur between localized active centers is modelled using a position- and orientation-dependent catalytic rate coefficient peaked about a maximum value a...

It is a significant feature of most gas-fluidized beds that they contain rising ‘bubbles’ of almost clear gas. The purpose of this paper is to account plausibly for this remarkable property first by supposing that primary and secondary instabilities of the fluidized bed generate compact regions of above-average or below-average particle concentrati...

A detailed asymptotic analysis accounting for wall curvature extends the Brenner-Gaydos formula for the hydrodynamic hindrance factor (J. Colloid Interface Sci. 1977, 58, 312-356) to terms of order λ2, yielding a new result of the form D̄/D∞ = (1 - λ)-2 [1 + (9/8)λ ln λ - 1.539λ + C2λ2 + o(λ2)], with C2 ≈ 1.2, where λ denotes the ratio of solute to...

Perturbation arguments are used to derive an approximate formula for partition coefficients of non-axisymmetric Y-shaped molecules in circular cylindrical pores. Quantitative accuracy thereof is verified by comparison with Monte Carlo calculations for star-shaped solutes. Results are used to calculate macroscopically observable partition coefficien...

In a previous paper we analysed the stability to small disturbances of stationary stratified fluid which is unbounded. Various forms of the undisturbed density distribution were considered, including a sinusoidal profile and a function of the vertical coordinate z which is constant outside a central horizontal layer. Both these types of stratificat...

Nitsche, J.M., 1992, New applications of Kahls' VLE analysis to engineering phase behavior calculations. Fluid Phase Equilibria, 78: 157-190.In a little known but profound paper, G.D. Kahl (1967) (Phys. Rev., 155: 78-80) developed a compelling argument questioning the validity of isothermal integration of the van der Waals equation between the spin...

A detailed investigation is presented of a model problem describing diffusion of a thin rod between parallel walls. Analysis proceeds by formulation of the exact diffusion equation in spatial and angular coordinates, and therefore accounts for all translational and rotational modes of transport. It is shown that the presence of a longitudinal conce...

Suppose that the density of stationary unbounded viscous fluid is a sinusoidal function of the vertical position coordinate z. Is this body of fluid gravitationally unstable to small disturbances, and, if so, under what conditions, and to what type of disturbance? These questions are considered herein, and the answers are that the fluid is indeed u...

Gorring (1973) reported a phenomenon, the “window effect,” whereby the diffusivities of normal paraffins within zeolite T do not decrease monotonically with increasing carbon number N, as would be expected intuitively. Rather, following an initial decrease with N, the diffusivities exhibit a local minimum at C8 followed by a pronounced local maximu...

Transport processes involving the motion of rigid nonspherical Brownian particles within porous media and, more generally, proximate to solid surfaces, arise in a multitude of natural and engineered contexts. Detailed modeling proceeds via solution of the microscale convective-diffusion equation in the six-dimensional configuration space composed o...

Monte Carlo simulation is used to calculate partition coefficients for rigid, axisymmetric, nonspherical molecules in various pore geometries. Novel quantitative results are presented for a variety of molecule and pore shapes, including pores of nonuniform cross-section such as the interstitial space within granular and fibrous materials.
Quick est...

A generalized Taylor dispersion analysis is presented of the combined diffusion and sedimentation of a Brownian particle subjected to a spatially periodic potential plus a uniform force. At long times this transport process is macroscopically characterized by a uniform mean drift velocity vector of the Brownian particle, and by a dispersion dyadic...

The sedimentation and diffusion of a nonneutrally buoyant Brownian particle in vertical fluid-filled cylinder of finite length which is instantaneously inverted at regular intervals are investigated analytically. A one-dimensional convective-diffusive equation is derived to describe the temporal and spatial evolution of the probability density; a p...

The Kleintjens—Koningsveld lattice-gas model is used to predict the phase behavior of pure CO2, water and decane, and of binary mixtures of CO2 with water and decane. The model, with parameters fitted to experimental data, predicts very accurate vapor pressures and liquid—vapor coexistence densities for the pure fluids. For the binary mixtures, the...

We compare phase behavior and surface tension predictions of the Kleintjens-Koningsveld (KK) equation of state, a lattice-gas model, with those of the Peng-Robinson (PR) equation, a van der Waals-like model. The KK equation, with parameters fitted to data, predicts accurately the vapor pressures, liquid-vapor coexistence densities, and the surface...