Effect of vehicle pretreatment on the flux, retention, and diffusion of topically applied penetrants in vitro

Purpose. The flux of a topically applied drug depends on the activity in the skin and the interaction between the vehicle and skin. Permeation of vehicle into the skin can alter the activity of drug and the properties of the skin barrier. The aim of this in vitro study was to separate and quantify these effects. Methods. The flux of four radiolabeled permeants (water, phenol, diflunisal, and diazepam) with log K-oct/water values from 1.4 to 4.3 was measured over 4 h through heat-separated human epidermis pretreated for 30 min with vehicles having Hildebrand solubility parameters from 7.9 to 23.4 (cal/cm(3))(1/2). Results. Enhancement was greatest after pretreatment with the more lipophilic vehicles. A synergistic enhancement was observed using binary mixtures. The flux of diazepam was not enhanced to the same extent as the other permeants, possibly because its partitioning into the epidermis is close to optimal (log K-oct 2.96). Conclusion. An analysis of the permeant remaining in the epidermis revealed that the enhancement can be the result of either increased partitioning of permeant into the epidermis or an increasing diffusivity of permeants through the epidermis.

GAIP participates in budding of membrane carriers at the trans-Golgi network

Galpha interacting protein (GAIP) is a regulator of G protein signaling protein that associates dynamically with vesicles and has been implicated in membrane trafficking, although its specific role is not yet known. Using an in vitro budding assay, we show that GAIP is recruited to a specific population of trans-Golgi network-derived vesicles and that these are distinct from coatomer or clathrin-coated vesicles. A truncation mutant (NT-GAIP) encoding only the N-terminal half of GAIP is recruited to trans -Golgi network membranes during the formation of vesicle carriers. Overexpression of NT-GAIP induces the formation of long, coated tubules, which are stabilized by microtubules. Results from the budding assay and from imaging in live cells show that these tubules remain attached to the Golgi stack rather than being released as carrier vesicles. NT-GAIP expression blocks membrane budding and results in the accumulation of tubular carrier intermediates. NT-GAIP-decorated tubules are competent to load vesicular stomatitis virus protein G-green fluorescent protein as post-Golgi, exocytic cargo and in cells expressing NT-GAIP there is reduced surface delivery of vesicular stomatitis virus protein G-green fluorescent protein. We conclude that GAIP functions as an essential part of the membrane budding machinery for a subset of post-Golgi exocytic carriers derived from the trans-Golgi network.

Microscopic structure of opalescent and nonopalescent pecans

The ultrastructure of pecans was investigated using light microscopy, environmental scanning electron microscopy, scanning electron microscopy, and transmission electron microscopy. Specific methodology for the sample preparation of pecans for electron microscopy investigations was developed. Electron microscopy of the ultrastructure of opalescent (discoloration of the interior) and nonopalescent kernels revealed that cellular damage was occurring in opalescent kernels. The damage was due to cell wall and membrane rupture, which accounted for the release of oil throughout the kernel. This rupture is due to the lower level of calcium in the cell membranes of opalescent pecans, as shown by energy dispersive X-ray spectrometry, making them more susceptible to damage.

Adsorption of supercritical fluids in non-porous and porous carbons: analysis of adsorbed phase volume and density

In this paper, we revisit the surface mass excess in adsorption studies and investigate the role of the volume of the adsorbed phase and its density in the analysis of supercritical gas adsorption in non-porous as well as microporous solids. For many supercritical fluids tested (krypton, argon, nitrogen, methane) on many different carbonaceous solids, it is found that the volume of the adsorbed phase is confined mostly to a geometrical volume having a thickness of up to a few molecular diameters. At high pressure the adsorbed phase density is also found to be very close to but never equal or greater than the liquid phase density. (C) 2003 Elsevier Science Ltd. All rights reserved.

Comparative study of the radiation-induced grafting of styrene onto poly(tetrafluoroethylene-co-perfluoropropylvinyl ether) and polypropylene substrates. I: Kinetics and structural investigation

A comparative study has been made of the radiation grafting of styrene onto poly(tetrafluoroethylene-co-perfluoropropyl vinyl ether) (PFA) and polypropylene (PP) substrates, using the simultaneous irradiation method. Effects of grafting conditions such as monomer concentrations, type of solvent, dose rate and irradiation dose on the grafting yield were investigated. Under the same grafting conditions it was found that a higher degree of grafting of styrene was obtained using a mixture of dichloromethane/methanol solvents for PFA and methanol for PP and the degree of grafting was higher in PP than in PFA at all doses. However, the micro-Raman spectroscopy analysis of the graft revealed that, for the same degree of grafting, the penetration depth of the grafted polystyrene into the substrate was higher in PFA than in PP substrates. In both polymers the crystallinity was hardly affected by the grafting process and the degree of crystallinity decreased slightly with grafting dose. The dependence of the initial rate of grafting on the dose rate and the monomer concentration was found to be 0.6 and 1.4 order for PFA and 0.15 and 2.2 for PP, respectively. The degree of grafting increased with increasing radiation dose in both polymers. However, the grafting yield decreased with an increase in the dose rate. The increase in the overall grafting yield for PFA and PP was accompanied by a proportional increase in the penetration depth of the graft into the substrates. (C) 2003 Society of Chemical Industry.

Cytotoxic iron chelators: Characterization of the structure, solution chemistry and redox activity of ligands and iron complexes of the di-2-pyridyl ketone isonicotinoyl hydrazone (HPKIH) analogues

Di-2-pyridyl ketone isonicotinoyl hydrazone (HPKIH) and a range of its analogues comprise a series of monobasic acids that are capable of binding iron (Fe) as tridentate (N,N,O) ligands. Recently, we have shown that these chelators are highly cytotoxic, but show selective activity against cancer cells. Particularly interesting was the fact that cytotoxicity of the HPKIH analogues is maintained even after complexation with Fe. To understand the potent anti-tumor activity of these compounds, we have fully characterized their chemical properties. This included examination of the solution chemistry and X-ray crystal structures of both the ligands and Fe complexes from this class and the ability of these complexes to mediate redox reactions. Potentiometric titrations demonstrated that all chelators are present predominantly in their charge-neutral form at physiological pH (7.4), allowing access across biological membranes. Keto-enol tautomerism of the ligands was identified, with the tautomers exhibiting distinctly different protonation constants. Interestingly, the chelators form low-spin (diamagnetic) divalent Fe complexes in solution. The chelators form distorted octahedral complexes with Fe-II, with two tridentate ligands arranged in a meridional fashion. Electrochemistry of the Fe complexes in both aqueous and non-aqueous solutions revealed that the complexes are oxidized to their ferric form at relatively high potentials, but this oxidation is coupled to a rapid reaction with water to form a hydrated (carbinolamine) derivative, leading to irreversible electrochemistry. The Fe complexes of the HPKIH analogues caused marked DNA degradation in the presence of hydrogen peroxide. This observation confirms that Fe complexes from the HPKIH series mediate Fenton chemistry and do not repel DNA. Collectively, studies on the solution chemistry and structure of these HPKIH analogues indicate that they can bind cellular Fe and enhance its redox activity, resulting in oxidative damage to vital biomolecules.

High energy radiation grafting of fluoropolymers

Fluoropolymers are known as chemically inert materials with good high temperature resistance, so they are often the materials of choice for harsh chemical environments. These properties arise because the carbon-fluorine bond is the strongest of all bonds between other elements and carbon, and, because of their large size, fluorine atoms can protect the carbon backbone of polymers such as poly(tetrafluoroethylene), PTFE, from chemical attack. However, while the carbon-fluorine bond is much stronger than the carbon hydrogen bond, the G values for radical formation on high energy radiolysis of fluoropolymers are roughly comparable to those of their protonated counterparts. Thus, efficient high energy radiation grafting of fluoropolymers is practical, and this process can be used to modify either the surface or bulk properties of a fluoropolymer. Indeed, radiation grafted fluoropolymers are currently being used as separation membranes for fuel cells, hydrophilic filtration membranes and matrix substrate materials for use in combinatorial chemistry. Herein we present a review of recent studies of the high energy radiation grafting of fluoropolymers and of the analytical methods available to characterize the grafts. (C) 2003 Elsevier Ltd. All rights reserved.

Analysis of multicomponent adsorption kinetics on activated carbon

An integrated mathematical model for the kinetics of multicomponent adsorption on microporous carbon was developed. Transport in this bidisperse solid is represented by balance equations in the macropore and micropore phases, in which gas-phase diffusion dominates the mass transfer in the macropores, with the phenomenological diffusivities represented by the generalized Maxwell-Stefan (GMS) formulation. Viscous flow also contributes to the macropore fluxes and is included in the MS expressions. Diffusion of the adsorbed phase controls the mass transfer in the micro ore phase, p which is also described in a similar way by the MS method. The adsorption isotherms are represented by a new heterogeneous modified vacancy solution theory formulation of adsorption, which has proved to be a robust method for adsorption on activated carbons. The model is applied to the coadsorption and codesorption of C2H6 and C3H8 on Ajax and Norit carbon, as well as the displacement on Ajax carbon. The effect of the viscous flow in the macropore phase is not significant for the cases studied. The model accurately predicts the overshoot behavior and rollup of C2H6 during coadsorption. The prediction for the heavier compound C3H8 is always satisfactory, though at higher C3H8 mole fraction, the overshoot extent of C2H6 is overpredicted, possibly due to neglect of heat effects.

An investigation of the thermal and tensile properties of PFA following γ-radiolysis

For some applications for fluoropolymers they must be subjected to high-energy radiation, e.g., when they are grafted with styrene using an irradiation method to produce fuel cell membranes or matrix supports for combinatorial chemistry. In some of these applications they may be subjected to mechanical stress or elevated temperature, so it is important to elucidate the effects of the radiolysis on these properties. In the present work the effect of gamma-radiolysis on the glass transition, melting behavior, and thermal stability of PFA has been studied as well as the effect of the radiolysis on the tensile properties of the polymer.

Investigation of the vapor-phase grafting of styrene onto PFA

Poly(tetrafluoroethylene-co-perfluoropropyI vinyl ether), PFA, was grafted with styrene from the vapor phase using a simultaneous radiation grafting method. The graft yields were measured as a function of the dose and dose rate and were found to be initially linearly dependent on the dose and independent of the dose rate up to dose rates of similar to3 kGy/h. However, at a dose rate of 6.2 kGy/h, the slope of the yield-grafting time plot decreased. Raman depth profiles of the grafts showed that the polystyrene concentrations were greatest near the surface of the grafted samples and decreased with depth. The maximum penetration depth of the graft depended on the radiation dose for a fixed dose rate. Fmoc-Rink loading tests showed that the grafts displayed superior loading compared to grafts prepared from bulk styrene or from styrene solutions other than methanol.