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Permeability Coefficients (permeability + coefficient)
Selected AbstractsEffect of solute lipophilicity on penetration through canine skinAUSTRALIAN VETERINARY JOURNAL, Issue 12 2003PC MILLS Objective To investigate the effect of lipophilicity on the percutaneous penetration of a homologous series of alcohols through canine skin Design Skin harvested from Greyhound thorax was placed in Franz-type diffusion cells and the in vitro passage of radio-labelled (14C) alcohols (ethanol, butanol, hexanol and octanol (Log P 0.19 - 3.0)) through separate skin sections was measured in replicates of five. Permeability coefficient (kP, cm/h), maximum flux (Jmax, mol/cm2/h) and residue remaining within the skin were determined. Results The kP increased with increasing lipophilicity (6.2 times 10 -4± 1.6 times 10 -4 cm/h for ethanol to 1.8 times 10 -2± 3.6 times 10 -3 cm/h for octanol). Alcohol residues remaining within each skin sample followed a similar pattern. An exponential decrease in Jmax with increasing lipophilicity was observed. Conclusion Changes in canine skin permeability occur with increasing alcohol lipophilicity. This finding has practical consequences for the design of topical formulations and optimisation of drug delivery through animal skin. [source] Flexible Ultrathin PolyDVB/EVB Composite Membranes for the Optimization of a Whole Blood Glucose SensorELECTROANALYSIS, Issue 4 2007Kerry Bridge Abstract An ultrathin composite membrane has been developed as the outer covering barrier in a model amperometric glucose oxidase enzyme electrode. The membrane was formed by cathodic electropolymerization of divinylbenzene/ethylvinylbenzene at the surface of a gold coated polyester support membrane. Permeability coefficients were determined for O2 and glucose across membranes with a range of polymer thicknesses. Anionic interferents (such as ascorbate), were screened from the working electrode via a charge exclusion mechanism. The enzyme electrode showed an initial 10% signal drift when first exposed to whole human blood over a period of 2 hours, after which responses remained essentially stable. Whole blood patient glucose determinations yielded a correlation coefficient of r2=0.99 compared to standard hospital analyses. [source] Polydivinylbenzene/Ethylvinylbenzene Composite Membranes for the Optimization of a Whole Blood Glucose SensorELECTROANALYSIS, Issue 1 2006Kerry Bridge Abstract A novel ultra thin polydivinylbenzene/ethylvinylbenzene composite membrane has been developed for use as the outer covering barrier in a model amperometric glucose oxidase enzyme electrode. The composite membrane was formed via the cathodic electropolymerization of divinylbenzene/ethylvinylbenzene at the surface of gold sputter coated host alumina membranes, (serving solely as a mechanical support for the thin polymer film). Permeability coefficients were determined for the enzyme substrates, O2 and glucose, across composite membranes formed with a range of polymer thicknesses. Due to the highly substrate diffusion limiting nature of the composite membrane, it was found that anionic interferents present in blood (such as ascorbate), were effectively screened from the working electrode via a charge exclusion mechanism, in a manner similar to previous findings within our laboratory. The enzyme electrode showed an initial 32% signal drift when first exposed to whole human blood over a period of 2 hours, after which time enzyme electrode responses remained essentially stable. Whole blood patient glucose determinations yielded a correlation coefficient of r2=0.97 in comparison to standard hospital analyses. [source] A novel route for preparation of PVC sheets with high UV irradiation resistanceJOURNAL OF APPLIED POLYMER SCIENCE, Issue 5 2010Xianke Ye Abstract A novel acrylonitrile acrylate copolymer coating was proposed to improve the UV irradiation resistance of poly(vinyl chloride) (PVC) sheets. Its effect on the photoageing properties of the sheets was evaluated by means of Fourier transform infrared (FTIR) spectroscopy, scanning electron microscopy (SEM), yellowness index test, and the oxygen permeability coefficient and mechanical properties measurement. The experimental results show that the novel acrylonitrile acrylate copolymer coating significantly improves the UV irradiation resistance of PVC sheets. Compared with the PVC sheets without coating, the coated PVC sheets show better mechanical properties, lower yellowness index, and smaller oxygen permeability coefficient after UV irradiation. The analysis on the SEM images of the PVC sheets indicates that the coating acts as a film to prevent the PVC sheets from UV energy and oxygen that can accelerate the photochemical reactions of PVC. The FTIR analysis confirms that the coating can slow down the microstructures development of the PVC sheets, also indicating that the coating impeded the photochemical reactions of PVC. © 2010 Wiley Periodicals, Inc. J Appl Polym Sci, 2010 [source] An investigation into the influence of counterion on the RS -propranolol and S -propranolol skin permeabilityJOURNAL OF PHARMACEUTICAL SCIENCES, Issue 3 2010Francesco Cilurzo Abstract The effects of two contra-ions, namely benzoate (Bz) and oleate (Ol), on the in vitro human skin permeability of propranolol racemate (RS -PR) or S -enantiomer (S -PR) were studied. Saline solution (SS) or mineral oil (MO) were selected as vehicles. The MO increased the permeability coefficient (Kp) of PR-Bz (pKp,,,4) of about four times with respect to SS (pKp,,,8) probably due to the ion pair formation. The steady-state flux of S -enantiomers resulted about twofold higher than that of racemates according to their lower melting temperatures with the exception of (S)-PR-Ol and (RS)-PR-Ol vehicled in SS which not resulted statistically different. This anomalous result could be explained considering the behavior of (RS)-PR-Ol or (S)-PR-Ol in aqueous solutions: these salts formed ion pairs which associated to form aggregates up to a concentration of 20,µg/mL as verified by light scattering. Therefore, their effective concentrations in SS resulted similar and justified the overlapped skin permeation profiles. All three considered variables, namely counterion, vehicle, and chirality, resulted mutually interfering on and deeply influenced the passive diffusion process of PR. © 2009 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 99: 1217,1224, 2010 [source] Human skin permeation and partition: General linear free-energy relationship analysesJOURNAL OF PHARMACEUTICAL SCIENCES, Issue 6 2004Michael H. Abraham Abstract Literature values of the permeability coefficient for permeation of human skin from water have been adjusted for ionization in water and adjusted for temperature. The obtained values of log Kp for 119 solutes at 37°C have been correlated with Abraham descriptors to yield an equation with R2,=,0.832 and SD,=,0.46 log units. Three separate test sets of 60 compounds had log Kp predicted with an SD of 0.48 log units. The main factors that influence log Kp are solute hydrogen bond basicity that lowers the permeability coefficient and solute volume that increases the permeability coefficient. Human skin,water partition coefficients, as log Ksc, have been collected for 45 compounds and yield an equation with R2,=,0.926 and SD,=,0.22 log units. We have compared the log Kp equation to equations for various other processes, but have found no process that appears to be similar to that for skin permeation. The nearest process to skin,water partition is the isobutanol,water partition system. An equation for lateral diffusion in the stratum corneum is shown to be reasonably close to various diffusion-related processes. © 2004 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 93:1508,1523, 2004 [source] Preparation and characterization of a customized cellulose acetate butyrate dispersion for controlled drug deliveryJOURNAL OF PHARMACEUTICAL SCIENCES, Issue 6 2002Siva Vaithiyalingam Abstract The purpose of the present experiment was to prepare and characterize the aqueous-based pseudolatex system of cellulose acetate butyrate (CAB) for controlled drug delivery. Aqueous pseudolatex systems are advantageous over organic-based coating systems because these systems are devoid of criteria pollutants such as carbon monoxide, nitrogen oxides, nonmethane volatile organic compounds, and sulfur dioxide. Pseudolatex was prepared with CAB and polyvinyl alcohol (stabilizer) by a polymer emulsification technique. The stability of pseudolatex was evaluated. Particle size was measured and rheological experiments were conducted. The glass transition temperature, microscopic free volume, permeation coefficient, and mechanical properties of plasticized pseudolatex films were estimated. Surface roughness of coating on inert Nu-Pareil® beads (Ingredient Technology Corp., Mahwah, NJ) was measured as a function of coating weight gain. The CAB Pseudolatex was found to be stabilized by steric forces. From intrinsic viscosity, the thickness of the stabilization layer was estimated. An increase in polymeric particles proportionately decreased the thickness of the stabilization layer. All the essential properties of a coating membrane such as microscopic free-volume fraction, permeability coefficient, mechanical properties, and glass transition temperature were fairly controllable as a function of plasticizer concentration. The pseudolatex dispersion of CAB was stable with negligible sedimentation volume and a particle size of 300 nm. Because CAB is water insoluble and non-ionizable, this pseudolatex can be used for pH-independent coating. The films obtained were strong and flexible for controlled drug delivery applications. Coating with the CAB dispersion reduced the surface roughness of beads but it remained stable as a function of increase in coating weight gain. © 2002 Wiley-Liss, Inc. and the American Pharmaceutical Association J Pharm Sci 91:1512,1522, 2002 [source] Influences of alkyl group chain length and polar head group on chemical skin permeation enhancementJOURNAL OF PHARMACEUTICAL SCIENCES, Issue 8 2001Kevin S. Warner Abstract Previous investigations in our laboratory on the influence of the n -alkanols and the 1-alkyl-2-pyrrolidones as skin permeation enhancers for steroid molecules as permeants demonstrated that the enhancer potencies (based on aqueous concentration values) of these two homologous series were the same when compared at the same alkyl chain length; that is, the contribution of the hydroxyl group and that of the pyrrolidone group to enhancer potency were the same. The purpose of the present study was to further investigate what was believed to be a somewhat surprising finding, and two additional homologous series, the 1,2-alkanediols and N,N -dimethylalkanamides, were selected for study as enhancers. Corticosterone (CS) flux enhancement along the lipoidal pathway of hairless mouse skin stratum corneum was determined with 1,2-hexane-, 1,2-octane-, and 1,2-decanediol and with N,N -dimethylhexanamide, N,N - dimethylheptanamide, N,N -dimethyloctanamide, and N,N -dimethylnonanamide as enhancers. The enhancement factor (E) for the lipoidal pathway was calculated from the CS permeability coefficient and the CS solubility data over a 4 to 100 range of E values. Comparisons of the enhancer potencies of all four homologous series revealed that the enhancer potencies of all were very nearly the same when compared at equal alkyl group chain length. Moreover, the contribution of each of the polar head groups toward the enhancer potency was essentially constant, independent of the alkyl group chain length. It was reasoned that this outcome was either the result of the random selection of four polar head groups making the same contribution to enhancer potency or the result of these particular polar head groups not contributing to enhancer potency. To test the hypothesis that the former was more likely than the latter and that a suitable semipolar organic phase may mimic the microenvironment of the polar head group at the site of enhancer action, n -octanol,phosphate buffered saline (PBS) and n -hexane,PBS partition coefficients were determined for all the enhancers. The n -octanol,PBS partition coefficients for the enhancers, but not the n -hexane,PBS partition coefficients, were very nearly the same when compared at equal alkyl group chain lengths; this result supports the hypothesis that each of the four polar head groups likely contributes the same toward the enhancer potency and locates in the semipolar region of the hairless mouse skin stratum corneum lipid bilayers, which is well-approximated by water-saturated n -octanol. © 2001 Wiley-Liss, Inc. and the American Pharmaceutical Association J Pharm Sci 90:1143,1153, 2001 [source] Permeability of a novel ,-lactamase inhibitor LK-157 and its ester prodrugs across rat jejunum in vitroJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 9 2009Petra Igli Abstract Objectives LK-157 is a novel 10-ethylidene tricyclic carbapenem that resembles the structure of the broad-spectrum antibiotic sanfetrinem and acts as a potent inactivator of ,-lactamases of classes A, C and D. LK-157 is a highly soluble but poorly permeable drug. Since most of the ,-lactams are poorly absorbed, ester prodrugs LK-159, LK-157E1 and LK-157E2 were designed to enhance membrane permeability. This study investigated the permeability of LK-157 and the three ester prodrugs across rat intestine in vitro. The morpholinoethyl ester of sanfetrinem was also investigated. Method Permeability across rat jejunum was determined using EasyMount side-by-side diffusion chambers. Key findings The solubility and permeability of morpholinoethyl ester LK-157E2 were superior to those of LK-159 and LK-157E1. The morpholinoethyl ester of sanfetrinem LK-176E1 had the highest observed permeability coefficient and consequently the highest predicted absorption in humans. Conclusions These results suggest that the morpholinoethyl esters of LK-157 and sanfetrinem could be further investigated to assess bioavailability in vivo. [source] Oxidative gating of water channels (aquaporins) in Chara by hydroxyl radicalsPLANT CELL & ENVIRONMENT, Issue 9 2004T. HENZLER ABSTRACT Hydroxyl radicals (*OH) as produced in the Fenton reaction (Fe2+ + H2O2 = Fe3+ + OH, + *OH) have been used to reversibly inhibit aquaporins in the plasma membrane of internodes of Chara corallina. Compared to conventional agents such as HgCl2, *OH proved to be more effective in blocking water channels and was less toxic to the cell. When internodes were treated for 30 min, cell hydraulic conductivity (Lp) decreased by 90% or even more. This effect was reversed within a few minutes after removing the radicals from the medium. In contrast to HgCl2, radical treatment reduced membrane permeability of small lipophilic organic solutes (ethanol, acetone, 1-propanol, and 2-propanol) by only 24 to 52%, indicating some continued limited movement of these solutes across aquaporins. The biggest effect of *OH treatment on solute permeability was found for isotopic water (HDO), which largely used water channels to cross the membrane. Inhibition of aquaporins reduced the diffusional water permeability (Pd) by about 70%. For the organic test solutes, which mainly use the bilayer to cross the membrane, channel closure caused anomalous (negative) osmosis; that is, cells had negative reflection coefficients (,s) and were transiently swelling in a hypertonic medium. From the ratio of bulk (Lp or osmotic permeability coefficient, Pf) to diffusional (Pd) permeability of water, the number (N) of water molecules that align in water channels was estimated to be N = Pf/Pd = 46 (on average). Radical treatment decreased N from 46 to 11, a value still larger than unity, which would be expected for a membrane lacking pores. The gating of aquaporins by *OH radicals is discussed in terms of a direct action of the radicals when passing the pores or by an indirect action via the bilayer. The rapid recovery of inhibited channels may indicate an easy access of cytoplasmic antioxidants to closed water channels. As hydrogen peroxide is a major signalling substance during different biotic and abiotic stresses, the reversible closure of water channels by *OH (as produced from H2O2 in the apoplast in the presence of transition metals such as Fe2+ or Cu+) may be downstream of the H2O2 signalling. This may provide appropriate adjustments in water relations (hydraulic conductivity), and a common response to different kinds of stresses. [source] Transport of aromatic solvents through nitrile rubber/epoxidized natural rubber blend membranesPOLYMER ENGINEERING & SCIENCE, Issue 3 2003Asha Elizabeth Mathai The sorption and diffusion behavior of a series of aromatic solvents through blends of nitrile rubber (NBR) and epoxidized natural rubber (ENR) have been studied in the temperature range of 28,70°C. The effect of blend ratio, penetrant size and temperature on the transport properties was investigated. The relationship between the diffusion behavior and the morphology of the system was examined. Different transport parameters such as diffusion coefficient, permeability coefficient and swelling ratio have been calculated. Experimental permeability coefficients were compared with various theoretical models. The van't Hoff relation was used to compute the thermodynamic parameters. [source] Metal ion permeation properties of silk fibroin/chitosan blend membranesPOLYMER INTERNATIONAL, Issue 4 2006Chun-Hui Du Abstract Silk fibroin/chitosan (SF/CS) blend membranes were prepared and characterized by infrared spectroscopy (FTIR), thermogravimetric analysis (TGA) and scanning electron microscopy. It was found that SF and CS were compatible in the blend membranes and that the membranes were dense without microscopic phase separation. Swelling experiments showed that the swelling ratio of the blend membranes increased with CS content and reached the highest value when CS content was 70 wt%. Experiments indicated that the permeability coefficient of K+ through the blend membrane was 2,4 times higher than that of pure CS membrane, and 10 times higher than that of pure SF membrane. The permeation rate of K+ increased linearly with CS content in the blend membrane for the lower concentration feeding solution. For different metal ions, the permeability through SF/CS blend membranes was in the sequence K+ > Ca2+ > Cd2+ > Pb2+ > Cu2+ > Ni2+. Copyright © 2006 Society of Chemical Industry [source] Insulin transport across porous charged membranes: Effect of the electrostatic interactionBIOTECHNOLOGY PROGRESS, Issue 5 2009Shaoling Zhang Abstract Insulin transport phenomena across a series of porous charged membranes were studied at two pH conditions (pH 3.3 and pH 7.4) in this article. The membranes were prepared by pore-surface modification of porous poly(acrylonitrile) (PAN) membranes by grafting with weak acidic and basic functional groups. The insulin partition coefficient K between the membrane and solution was estimated from the equilibrium adsorption amount in the batch adsorption experiment. The insulin effective diffusion coefficient D inside the membrane was determined as a fitting parameter by matching the diffusion model with the experimental data of the diffusion measurement. Both K and D correlated well with the charge properties of the insulin and membrane: when the insulin and membrane carried opposite net charge, the partition coefficient showed relatively larger values, while the effective diffusion coefficient was reduced. The insulin permeability coefficient P obtained from the experimental results agreed with that estimated from the partition coefficient and effective diffusion coefficient. These results suggested that the combined effects of the solubility and diffusivity on the permeability coefficient complicated the relationship between the permeability and the charge properties of the insulin and membrane. Additionally, our calculation supported that insulin permeability was reduced by the boundary layer between the membrane and solution. © 2009 American Institute of Chemical Engineers Biotechnol. Prog., 2009 [source] Photoswitchable Gas Permeation Membranes Based on Liquid CrystalsADVANCED FUNCTIONAL MATERIALS, Issue 17 2010Eric G, owacki Abstract We have fabricated switchable gas permeation membranes in which a photoswitchable low-molecular-weight liquid crystalline (LC) material acts as the active element. Liquid crystal mixtures are doped with mesogenic azo dyes and infused into commercially available track-etched membranes with regular cylindrical pores (0.40 to 10.0 ,m). Tunability of mass transfer can be achieved through a combination of (1) LC/mesogenic dye composition, (2) surface-induced alignment, and (3) reversible photoinduced LC-isotropic transitions. Photo-induced isothermal phase changes in the imbibed material afford large and fully reversible changes in the permeability of the membrane to nitrogen. Both the LC and photogenerated isotropic states demonstrate a linear permeability/pressure relationship, but they show significant differences in their permeability coefficients. Liquid crystal compositions can be chosen such that the LC phase is more permeable than the isotropic,or vice versa , and can be further tuned by surface alignment. Permeability switching response times are 5 s, with alternating UV and >420-nm radiation at an intensity of 2 mW/cm2 being sufficient for complete and reversible switching. Thermal and kinetic properties of the confined LC materials are evaluated and correlated with the observed permeation properties. We demonstrate for the first time reversible permeation control of a membrane with light irradiation. [source] Gas breakthrough experiments on fine-grained sedimentary rocksGEOFLUIDS (ELECTRONIC), Issue 1 2002A. Hildenbrand Abstract The capillary sealing efficiency of fine-grained sedimentary rocks has been investigated by gas breakthrough experiments on fully water saturated claystones and siltstones (Boom Clay from Belgium, Opalinus Clay from Switzerland and Tertiary mudstone from offshore Norway) of different lithological compositions. Sand contents of the samples were consistently below 12%, major clay minerals were illite and smectite. Porosities determined by mercury injection lay between 10 and 30% while specific surface areas determined by nitrogen adsorption (BET method) ranged from 20 to 48 m2 g , 1. Total organic carbon contents were below 2%. Prior to the gas breakthrough experiments the absolute (single phase) permeability (kabs) of the samples was determined by steady state flow tests with water or NaCl brine. The kabs values ranged between 3 and 550 nDarcy (3 × 10,21 and 5.5 × 10,19 m2). The maximum effective permeability to the gas-phase (keff) measured after gas breakthrough on initially water-saturated samples extended from 0.01 nDarcy (1 × 10,23 m2) up to 1100 nDarcy (1.1 × 10,18 m2). The residual differential pressures after re-imbibition of the water phase, referred to as the ,minimum capillary displacement pressures' (Pd), ranged from 0.06 to 6.7 MPa. During the re-imbibition process the effective permeability to the gas phase decreases with decreasing differential pressure. The recorded permeability/pressure data were used to derive the pore size distribution (mostly between 8 and 60 nm) and the transport porosity of the conducting pore system (10 -5,10 -2%). Correlations could be established between (i) absolute permeability coefficients and the maximum effective permeability coefficients and (ii) effective or absolute permeability coefficients and capillary sealing efficiency. No correlation was found between the capillary displacement pressures determined from gas breakthrough experiments and those derived theoretically by mercury injection. [source] Sorption and permeation behavior for CO2 in NH3 -plasma-treated and untreated polystyrene membranesJOURNAL OF APPLIED POLYMER SCIENCE, Issue 3 2007Y.-S. Yang Abstract In our preceding work, the simultaneous deviation from the conventional dual-mode sorption and mobility model was observed in a case of CO2 in polystyrene (PS) membrane (glass transition temperature of pure polymer = 95°C) at 60 and 70°C. The plasticization effect of sorbed CO2 on both the sorption and diffusion processes tends to be brought about in glassy polymer membranes near the glass transition temperature. The behavior was simulated based on the concept that only one population of sorbed gas molecules of plasticizing ability to the polymer should exist. In the present work, the sorption and permeation behavior for CO2 in NH3 -plasma-treated and untreated PS membranes at 40°C was investigated, where NH3 -plasma treatment was executed at plasma discharge powers of 40, 80, 120, and 160 W for an exposure time of 2 min. The sorption isotherm could be described by the sorption theory of Mi et al. (Macromolecules 1991, 24, 2361), where the glass transition temperature is depressed by a concentration of sorbed CO2 of plasticizing ability. NH3 -plasma treatment on PS membrane had little influence on the sorption behavior of CO2 at plasma discharge powers up to 160 W. The mean permeability coefficients were somewhat increased only at a discharge power of 160 W. At CO2 pressures below 0.9 MPa, the pressure dependencies of mean permeability coefficients for CO2 in both NH3 -plasma-treated and untreated PS membranes at 40°C could also be simulated on the basis of the concept that only one population of sorbed gas molecules of plasticizing ability should exist. At CO2 pressures above 0.9 MPa, however, a plasticization action of sorbed CO2 had much more influence on the diffusion process rather than on the sorption one, and such a combined concept underestimated the mean permeability coefficient. © 2006 Wiley Periodicals, Inc. J Appl Polym Sci 103: 1798,1805, 2007 [source] Liposome transport of hydrophobic drugs: Gel phase lipid bilayer permeability and partitioning of the lactone form of a hydrophobic camptothecin, DB-67JOURNAL OF PHARMACEUTICAL SCIENCES, Issue 1 2008Vijay Joguparthi Abstract The design of liposomal delivery systems for hydrophobic drug molecules having improved encapsulation efficiency and enhanced drug retention would be highly desirable. Unfortunately, the poor aqueous solubility and high membrane binding affinity of hydrophobic drugs necessitates extensive validation of experimental methods to determine both liposome loading and permeability and thus the development of a quantitative understanding of the factors governing the encapsulation and retention/release of such compounds has been slow. This report describes an efflux transport method using dynamic dialysis to study the liposomal membrane permeability of hydrophobic compounds. A mathematical model has been developed to calculate liposomal membrane permeability coefficients of hydrophobic compounds from dynamic dialysis experiments and partitioning experiments using equilibrium dialysis. Also reported is a simple method to study the release kinetics of liposome encapsulated camptothecin lactone in plasma by comparing the hydrolysis kinetics of liposome entrapped versus free drug. DB-67, a novel hydrophobic camptothecin analogue has been used as a model permeant to validate these methods. Theoretical estimates of DB-67 permeability obtained from the bulk solubility diffusion model and the "barrier-domain" solubility diffusion model are compared to the experimentally observed value. The use of dynamic dialysis in drug release studies of liposome and other nanoparticle formulations is further discussed and experimental artifacts that can arise without adequate validation are illustrated through simulations. © 2007 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 97:400,420, 2008 [source] Comparison of the effects of chemical permeation enhancers on the lipoidal pathways of human epidermal membrane and hairless mouse skin and the mechanism of enhancer actionJOURNAL OF PHARMACEUTICAL SCIENCES, Issue 9 2007Doungdaw Chantasart Abstract Previously, the effects of chemical permeation enhancers upon the permeability of the lipoidal pathway of hairless mouse skin (HMS) were investigated and a quantitative structure enhancement relationship was established. The present study was to study the effects of these enhancers on human epidermal membrane (HEM) using the same experimental method employed in the previous HMS studies. The effects of enhancers on the permeability coefficients of the lipoidal pathways of HEM and HMS for corticosterone were found to be essentially the same. In the equilibrium uptake studies of the enhancers and ,-estradiol, it was found that the amounts of enhancers taken up and the partitioning of ,-estradiol into the HEM stratum corneum (SC) intercellular lipid under the E,=,10 conditions were different from those of HMS. Despite these differences, the HEM data show a correlation between the intercellular lipid/PBS partition coefficients of the enhancers and the enhancer n-octanol/PBS partition coefficients. This correlation is consistent with the observed chemical microenvironment of the site of enhancer action in the HMS SC in previous studies. Therefore, provided with proper experimental protocols, HMS can be a reliable model for the evaluation of the effects of skin permeation enhancers on the lipoidal pathway of HEM. © 2007 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 96: 2310,2326, 2007 [source] QSAR analysis of interstudy variable skin permeability based on the "latent membrane permeability" conceptJOURNAL OF PHARMACEUTICAL SCIENCES, Issue 10 2003Shin-Ichi Fujiwara Abstract A number of QSAR models for skin permeability have been proposed, but these models lack consistency due to interspecies and interlaboratory differences. This study was initiated to extract an essential QSAR from the multiplicity of data sets of skin permeability by using a novel statistical approach. Ten data sets were collected from the literature, which include a total of 111 permeability coefficients in human, hairless mouse, or hairless rat skin for 94 structurally diverse compounds. Following a Potts and Guy's approach, the octanol/water partition coefficient and molecular weight were chosen as molecular descriptors. All of the data sets were analyzed simultaneously, assuming that all of the sets share a latent, common factor as far as the structure/permeability relationship is concerned. Despite the fact that the degree-of-freedom for the present analysis was limited compared with that for individual regression analyses, the determination coefficients (R2) were high enough for all the 10 data sets, with an average R2 of 0.815 (average R2,=,0.825 for individual analyses). Thus, skin permeability of compounds can be well explained from the log P and M.W., where the ratio of the contribution to skin permeability was approximately 1:1. © 2003 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 92:1939,1946, 2003 [source] Transport of aromatic solvents through nitrile rubber/epoxidized natural rubber blend membranesPOLYMER ENGINEERING & SCIENCE, Issue 3 2003Asha Elizabeth Mathai The sorption and diffusion behavior of a series of aromatic solvents through blends of nitrile rubber (NBR) and epoxidized natural rubber (ENR) have been studied in the temperature range of 28,70°C. The effect of blend ratio, penetrant size and temperature on the transport properties was investigated. The relationship between the diffusion behavior and the morphology of the system was examined. Different transport parameters such as diffusion coefficient, permeability coefficient and swelling ratio have been calculated. Experimental permeability coefficients were compared with various theoretical models. The van't Hoff relation was used to compute the thermodynamic parameters. [source] Modeling of structural reaction injection molding process.POLYMER ENGINEERING & SCIENCE, Issue 5 2001A mathematical model of the infusion process in producing reinforced articles is proposed. The model is based on the analysis of flow of a Newtonian liquid inside a rectangular multilayer channel. According to the model, a liquid enters the central (feeding) layer, moves through this layer, and simultaneously impregnates peripheral layers. So, the flow is two-dimensional. Flow inside the porous layers is treated in terms of the Darcy equation with different permeability coefficients in two directions. Principal solutions for the flow front development and pressure evolution were obtained and analyzed. Then the initial model, developed for a Newtonian liquid, is generalized for the so-called "rheokinetic" liquid, which changes its rheological properties in time as a result of temperature variation and/or any possible chemical process, in particular, the reaction of curing of a binder. It was proven that in this case the solution is automodel. This means that the solutions obtained for a Newtonian liquid in the dimensionless form are valid for an arbitrary rheokinetic liquid. [source] Biocompatibility and Calcification of Bovine Pericardium Employed for the Construction of Cardiac Bioprostheses Treated With Different Chemical Crosslink MethodsARTIFICIAL ORGANS, Issue 5 2010Eduardo Jorge-Herrero Abstract The use of biological materials in the construction of bioprostheses requires the application of different chemical procedures to improve the durability of the material without producing any undesirable effects. A number of crosslinking methods have been tested in biological tissues composed mainly of collagen. The aim of this study was to evaluate the in vitro biocompatibility, the mechanical properties, and in vivo calcification of chemically modified bovine pericardium using glutaraldehyde acetals (GAAs) in comparison with glutaraldehyde (GA) treatment. Homsy's tests showed that the most cytotoxic treatment is GA whereas GAA treatments showed lower cytotoxicity. Regarding the mechanical properties of the modified materials, no significant differences in stress at rupture were detected among the different treatments. Zeta-Potential showed higher negative values for GA treatment (,4.9 ± 0.6 mV) compared with GAA-0.625% (,2.2 ± 0.5 mV) and GAA-1% (,2.2 ± 0.4 mV), which presented values similar to native tissue. Similar results were obtained for calcium permeability coefficients which showed the highest values for GA treatment (0.12 ± 0.02 mm2/min), being significantly lower for GAA treatments or non-crosslinked pericardium. These results confirmed the higher propensity of the GA-treated tissues for attraction of calcium cations and were in good agreement with the calcification degree obtained after 60 days implantation into young rats, which was significantly higher for the GA group (22.70 ± 20.80 mg/g dry tissue) compared with GAA-0.625% and GAA-1% groups (0.49 ± 0.28 mg/g dry tissue and 3.51 ± 3.27 mg/g dry tissue, respectively; P < 0.001). In conclusion, GAA treatments can be considered a promising alternative to GA treatment. [source] Toluene diisocyanate enhances human bronchial epithelial cells' permeability partly through the vascular endothelial growth factor pathwayCLINICAL & EXPERIMENTAL ALLERGY, Issue 10 2009H. Zhao Summary Background Toluene diisocyanate (TDI) is a recognized chemical asthmogen; yet, the mechanisms of its toxicity have not been elucidated. Objective To investigate the influence of TDI on the permeability of human bronchial epithelial cell (HBE; HBE135-E6E7) monolayers in vitro, and the expression of vascular endothelial growth factor (VEGF) in these cells. Methods TDI,human serum albumin (HSA) conjugates were prepared by a modification of Son's method. Fluorescein isothiocyanate-labelled dextran and transmission electron microscopy were used to evaluate the effects of TDI,HSA on HBE135-E6E7 permeability. RT-PCR and ELISA were used to evaluate VEGF gene expression and protein release from HBE135-E6E7 cells stimulated by TDI,HSA. A VEGF-neutralizing antibody was used in monolayer permeability experiments to determine the role of the VEGF pathway in this process. Results TDI,HSA significantly increased the permeability coefficients of HBE135-E6E7 monolayers (P<0.01). TDI,HSA treatment significantly increased the expression of VEGF165 and VEGF189 genes (P<0.01). ELISA showed that TDI significantly induces VEGF release from HBE135-E6E7 cells. Cells treated with TDI,HSA and VEGF-neutralizing antibody had significantly lower permeability coefficients than cells treated with TDI,HSA only (P<0.01), but still significantly higher than control cells (P<0.01). Cells treated with TDI,HSA had fewer tight junctions (TJs) than control and HSA-treated cells, and addition of the anti-VEGF antibody did not restore the original number of TJs. Conclusion TDI increases the permeability of HBE cell monolayers, partly through a VEGF-mediated pathway. This suggests the importance of VEGF in TDI-induced pulmonary diseases, but shows that other pathways may be involved in the pathogenic process. [source] | |||||||||||||||||||