Iontophoretic Transport of Model Compounds from a Gel Matrix Across a Cellophane Membrane

Drug release rates from hydrogels through cellophane membranes were determined using custom-built diffusion cells which were modified to allow the application of current across the membranes. In the absence of a current the results obtained using different concentrations of drug and of the gel indicate the release to be matrix-controlled with a linear relationship between the quantities of drug released and the square root of release time. When a range of direct currents was applied enhanced transport was observed and as the current was increased the release curves became linear with time. The rate of release was also found to increase linearly with the current strength. These results show that an electrical current may be used to increase the rate of drug transport and to alter its release profile under conditions when the unassisted release is matrix rather than membrane controlled.     

Transdermal Iontophoretic Delivery of Thyrotropin-Releasing Hormone Across Excised Rabbit Pinna Skin

Abstract

Enhanced transport of a model peptide drug thyrotropin-releasing hormone (TRH), a tripeptide of molar mass 362 g and a pK_a 6.2, through excised rabbit pinna skin was achieved by means of iontophoresis with continuous current or monophase periodically pulsed current. The resulting flux in the steady state was proportional to the applied current density. In the transdermal iontophoretic delivery of TRH, the pulsed iontophoretic flux exceeded that obtained with a continuous current. At a low ionic strength, an increased degree of protonation in TRH increased the rate of permeation. The flux of TRH in a buffer at pH 4 is greater than that at pH 8 when the ionic strength is 0.1 M. At a greater ionic strength, the trend is reversed. The enhanced flux of unprotonated TRH during transdermal iontophoresis is attributed largely to electro-osmotic volume flow. An increased rate of permeation of TRH crossing the skin is achieved at low ionic strength, moderate pH, and a large duly cycle of current; the frequency of pulsed current had no significant influence on the rate of transdermal iontophoretic delivery of TRH.     

Transdermal Iontophoretic Delivery of Thyrotropin-Releasing Hormone Across Excised Rabbit Pinna Skin

Enhanced transport of a model peptide drug thyrotropin-releasing hormone (TRH), a tripeptide of molar mass 362 g and a pK_a 6.2, through excised rabbit pinna skin was achieved by means of iontophoresis with continuous current or monophase periodically pulsed current. The resulting flux in the steady state was proportional to the applied current density. In the transdermal iontophoretic delivery of TRH, the pulsed iontophoretic flux exceeded that obtained with a continuous current. At a low ionic strength, an increased degree of protonation in TRH increased the rate of permeation. The flux of TRH in a buffer at pH 4 is greater than that at pH 8 when the ionic strength is 0.1 M. At a greater ionic strength, the trend is reversed. The enhanced flux of unprotonated TRH during transdermal iontophoresis is attributed largely to electro-osmotic volume flow. An increased rate of permeation of TRH crossing the skin is achieved at low ionic strength, moderate pH, and a large duly cycle of current; the frequency of pulsed current had no significant influence on the rate of transdermal iontophoretic delivery of TRH.     

A Physical Compact Model for Electron Transport Across Single Molecules

Prediction of current flow across single molecules requires ab initio electronic structure calculations along with their associated high computational demand, and a means for incorporating open system boundary conditions to describe the voltage sources driving the current. To date, first principle predictions of electron transport across single molecules have not fully achieved a predictive capability. The situation for molecular electronics may be compared to conventional technology computer-aided design (TCAD), whereby various approximations to the Boltzmann transport equation are solved to predict electronic device behavior, but in practice are too time consuming for most circuit design applications. To simplify device models for circuit design, analytical but physically motivated models are introduced to capture the behavior of active and passive devices; however, similar models do not yet exist for molecular electronics. We follow a similar approach by evaluating an analytical model achieved by combining a mesoscopic transport model with parameterizations taken from quantum chemical calculations of the electronic structure of single molecule bonded between two metal contacts. Using the model to describe electron transport across benzene-1,4-dithiol and by comparing to experiment, we are able to extract the coupling strength of the molecule attached to two infinite metal electrodes. The resulting procedure allows for accurate and computationally efficient modeling of the static (dc) characteristics of a single molecule, with the added capability of being able to study the physical model parameter variations across a range of experiments. Such simple physical models are also an important step towards developing a design methodology for molecular electronics     

The Enhanced Iontophoretic Transport of TRH and Its Impedance Study

Abstract

The transdermal drug delivery of iontophoresis provides a noninvasive method for the administration of effective drugs. The enhanced iontophoretic transport of thyrotropin-releasing hormone (TRH), a tripeptide with molecular weight of 362 and a pK_a of 6.2, through an excised rabbit skin has been achieved by in vitro iontophoresis. The results indicate that the steady-state flux of TRH in a diffusion cell is proportional to the current density. In addition, the electrochemical properties of rabbit skin were studied with impedance spectroscopy, and it was found that the skin impedance decreased to a low and stable value with respect to its initial skin impedance while a current was applied through the rabbit skin. This is in good agreement with our experimental results on iontophoretic transport. As compared to passive diffusion, the iontophoresis dramatically increased the transport fluxes of TRH, and ethanol pretreatment further enhanced its iontophoretic transport. A practical implication of these results is that iontophoresis with a chemical permeation enhancer (ethanol pretreatment) can be applied to enhance and control the transdermal delivery of peptides.     

The Enhanced Iontophoretic Transport of TRH and Its Impedance Study

The transdermal drug delivery of iontophoresis provides a noninvasive method for the administration of effective drugs. The enhanced iontophoretic transport of thyrotropin-releasing hormone (TRH), a tripeptide with molecular weight of 362 and a pK_a of 6.2, through an excised rabbit skin has been achieved by in vitro iontophoresis. The results indicate that the steady-state flux of TRH in a diffusion cell is proportional to the current density. In addition, the electrochemical properties of rabbit skin were studied with impedance spectroscopy, and it was found that the skin impedance decreased to a low and stable value with respect to its initial skin impedance while a current was applied through the rabbit skin. This is in good agreement with our experimental results on iontophoretic transport. As compared to passive diffusion, the iontophoresis dramatically increased the transport fluxes of TRH, and ethanol pretreatment further enhanced its iontophoretic transport. A practical implication of these results is that iontophoresis with a chemical permeation enhancer (ethanol pretreatment) can be applied to enhance and control the transdermal delivery of peptides.     

Gel Materials from Fullerene-Silane Compounds and their Optical Nonlinearities

Two fullerene-silane compounds and their corresponding gels were synthesized. The maximum molar ratio of C₆₀Si in the gel can reach a value of 1.6 × 10^-3. The optical nonlinearity of the obtained gel under picosecond excitation at 1.06μm has been studied primarily by the Z-scan technique.     

江河竞渡的优化模型

首先建立了江水流速恒定不变的模型I,得出了2002年冠军选手的行进路线为连接起点与终点的直线,其速度大小约为1.54米/秒,方向为垂直对岸左偏27.5°;近似求出了速度为1.5米/秒的选手的前进方向应左偏31.9°,他的最好成绩约为15分10秒;根据此模型,得出了1934年和2002年成功完成赛事的最低速度及可以选择的前进角度,较好地解释了两次比赛成功者比例相差悬殊的原因,进而得出了能够垂直游向对岸的条件为v≥uY/X.在模型I的基础上,建立了江水速度分段变化的模型Ⅱ,回答了题目的问题3--选手的前进方向为靠近两岸200米之内时,左偏36.1°,在江心区域左偏28.1°;它的最好成绩大约为15分4秒.进一步,我们又完成了江水流速按区域连续变化的模型Ⅲ和模型Ⅳ,并用离散的方法求解了该模型.根据运算结果,为选手提供了在垂直距离上每前行100米所应调整的角度,求得最优路径为一"反S"型;得出了"两侧偏角大,中间偏角小"的行进方向基本原理.     

Dielectric Properties of a Printed Sol–Gel Matrix Composite

Low temperature processable materials with high dielectric constants are required for application on flexible organic substrates, for example, in printed electronics. To date, mainly organic polymers with embedded functional particles have been investigated for this purpose. For the first time, we present a printable dielectric composite material composed of ferroelectric high permittivity particles (BaTiO₃) bonded by a mainly inorganic sol–gel derived network. The exemplary optimization of the properties by varying the sol–gel precursor illustrates the potential of sol–gel chemistry for printable functional materials. An operational gravure printed capacitor including printed silver electrodes is presented. The measured dielectric constants are among the highest reported in literature for low temperature cured films with moderate dissipation factors. Besides these promising dielectric properties, this composite film shows a ferroelectric response.     

江河竞渡的优化模型

首先建立了江水流速恒定不变的模型Ⅰ,得出了2002年冠军选手的行进路线为连接起点与终点的直线,其速度大小约为1.54米/秒,方向为垂直对岸左偏27.5°;近似求出了速度为1.5米/秒的选手的前进方向应左偏31.9°,他的最好成绩约为15分10秒;根据此模型,得出了1934年和2002年成功完成赛事的最低速度及可以选择的前进角度,较好地解释了两次比赛成功者比例相差悬殊的原因,进而得出了能够垂直游向对岸的条件为v>uY/X。在模型Ⅰ的基础上,建立了江水速度分段变化的模型Ⅱ,回答了题目的问题3——选手的前进方向为靠近两岸200米之内时,左偏36.1°,在江心区域左偏28.1°;它的最好成绩大约为15分4秒。 进一步,我们又完成了江水流速按区域连续变化的模型Ⅲ和模型Ⅳ,并用离散的方法求解了该模型。根据运算结果,为选手提供了在垂直距离上每前行100米所应调整的角度,求得最优路径为-“反S”型;得出了“两侧偏角大,中间偏角小”的行进方向基本原理。     

Iontophoretic in Vitro Release of Antimycotics from Hydrogels

A new in vitro model for iontophoretic release from hydrogels was developed. It represents a modification of the rotary disk cell developed by Moll/Bender and can be used in a normal dissolution tester. The iontophoretic release from antimycotic hydrogels through an artificial membrane was investigated and different types of antimycotics were tested. The influence of current density, drug concentration and vehicle was determined.     

Transport Characteristics of a Beta Sheet Breaker Peptide Across Excised Bovine Nasal Mucosa

ABSTRACT

The purpose of the present study was to investigate the permeation characteristics of the beta sheet breaker peptide AS 602704 (BSB) on excised bovine nasal mucosa using an Ussing chamber model. The influence of various absorption enhancers such as sodium cholate, sodium dodecyl sulfate (SDS), cetrimidum, sodium caprate, Na₂EDTA, polycarbophil (PCP), the thiomer conjugate polycarbophil-cysteine (PCP-Cys), and poly-l-arginine (poly-l-arg; 100 kDa) was evaluated. Additionally, the influence of temperature and pH on the transport rate as well as the stability of the peptide drug against enzymatic degradation were investigated in vitro.

The effective permeability coefficient (P_eff) of BSB in Krebs-Ringer-buffer (KRB) pH 7.4 was (1.89 ± 0.44)* 10^?5, while in the presence of sodium caprate (0.5%) a P_eff of (9.58 ± 1.82)*10^?5 was achieved. Rank order of enhancement ratio was sodium caprate > SDS > sodium cholate > Na₂EDTA > poly-l-arg = PCP-Cys. In case of cetrimidum and PCP even a decrease in the absorption of BSB was determined. Na₂EDTA reduced the enzymatic degradation of BSB when exposed to a nasal tissue homogenate by more than the half. An increased lipophilicity of BSB because of a more acidic milieu (pH 5.5) did not lead to an increased transcellular transport. Permeation studies carried out at 4°C compared to 37°C demonstrated a temperature dependent permeation behaviour suggesting an additional active carrier mediated transport.

The results obtained within these studies should facilitate the development of a nasal delivery system for AS 602704 for the treatment of Alzheimer's disease.     

The Transport of Tetracyclines Across Protein Gels and Sols

The transport of tetracyclines across various model mucus systems has been studied in a three compartment permeability cell. Commercially available hog gastric mucin hydrated in buffer or a buffer containing tetraborate ions to crosslink the gel produced transport rates that were very different from samples of homogenized bronchial mucus. When albumin was substituted for mucus, correlation was obtained for the lag time and the number of moles of tetracycline bound per mole of protein.     

Feasibility of a DNA-Based Combinatorial Array Recognition Surface (CARS) in a Polyacrylamide Gel Matrix

We report initial attempts at developing a self-assembled combinatorial DNA biosensor array which may be capable of binding and identifying virtually any soluble analyte that binds the array by pattern recognition, in effect making it a universal biosensor surface. Data are presented for differential binding patterns of various analytes to 1-D arrays of combinatorial deoxyribonucleic acid (DNA) concatamer libraries which are spatially separated according to size and charge by electrophoresis in polyacrylamide gels. These DNA concatamer libraries are essentially composed of single-stranded (ss) random DNA 60 mers, which form a ldquosmearrdquo pattern in gels following electrophoresis. When used to bind and detect various analytes or mixtures of analytes in the gel, we refer to the DNA smear as a ldquocombinatorial array recognition surfacerdquo (CARS). Differences in intrinsic fluorescence scanning patterns of CARS gel strips were compared before and after addition of various analytes to the arrays to detect binding patterns. Scans revealed a high level of reproducibility for individual CARS arrays in a given gel with or without bound analytes. Scan patterns between different CARS gel strips were initially less reproducible, but purification of the DNA library using spin columns prior to electrophoresis improved gel-to-gel reproducibility.     

Transport of Methotrexate Dialkyl Ester Prodrugs Across Full-Thickness Hairless Mouse Skin

The permeability coefficients of methotrexate (MTX) and a series of its mono and dialky¹ ester prodrugs across full-thickness hairless mouse skin have been determined using an in vitro diffusion method. MTX was found to permeate across this skin model with a mean permeability of 5.6x10^-5 cm/hr. Monoesterification only slightly improved MTX permeation and the effect appeared to be invariant with alky¹ chain length. Diesterification of MTX, on the other hand, resulted in derivatives prone to simultaneous conversion during permeation by both skin esterase and chemical hydrolysis in the diffusion medium. The contribution of conversion to overall MTX diffusion was treated mathematically in order to calculate the intrinsic permeabilities of MTX dialky¹ esters. It was found that the dialky¹ esters showed a parabolic permeability versus chain length relationship with the dimethy¹ ester being the most permeable compound.