SDS-Based Biomembrane Mimetic Chromatography for Prediction of Human Drug Transport as an in Vitro Technique

The main oral drug absorption barriers are fluid cell membranes, and generally drugs are absorbed by a passive diffusion mechanism. On the other hand, the blood–brain barrier (BBB) is considered to be the main barrier to drug transport into the central nervous system (CNS). The BBB restricts the passive diffusion of many drugs from blood to brain. Biopartitioning micellar chromatography (BMC), a mode of micellar liquid chromatography that uses micellar mobile phases in adequate experimental conditions, can be useful as an in vitro system in mimicking the drug partitioning process into biological systems. In this study, relationships between the BMC retention data of a heterogeneous set of 12 drugs and their pharmacokinetics parameters (human oral drug absorption and BBB penetration ability) are studied and the predictive ability of the models is evaluated. Modeling of log k _BMC of these compounds was established by multiple linear regression in two different concentrations (0.07 and 0.09 M) of sodium dodecyl sulfate (SDS). The results showed a fair correlation between human oral drug absorption and BMC retention data in 0.09 M SDS (R ² = 0.864) and a good correlation between the blood–brain distribution coefficient and BMC retention data in 0.07 M of SDS (R ² = 0.887). Application of the developed models to a prediction set demonstrated that the model is also reliable with good predictive accuracy. The external and internal validation results showed that the predicted values are in good agreement with the experimental value.

     

New method based on combining ultrasonic assisted miniaturized matrix solid-phase dispersion and homogeneous liquid-liquid extraction for the determination of some organochlorinated pesticides in fish

In this study, ultrasonic assisted miniaturized matrix solid-phase dispersion (US-MMSPD) combined with homogeneous liquid–liquid extraction (HLLE) has been developed as a new method for the extraction of organochlorinated pesticides (OCPs) in fish prior to gas chromatography with electron capture detector (GC-ECD). In the proposed method, OCPs (heptachlor, aldrin, DDE, DDD, lindane and endrin) were first extracted from fish sample into acetonitrile by US-MMSPD procedure, and the extract was then used as consolute solvent in HLLE process. Optimal condition for US-MMSPD step was as follows: volume of acetonitrile, 1.5 mL; temperature of ultrasound, 40 °C; time of ultrasound, 10 min. For HLLE step, optimal results were obtained at the following conditions: volume of chloroform, 35 μL; volume of aqueous phase, 1.5 mL; volume of double distilled water, 0.5 mL; time of centrifuge, 10 min. Under the optimum conditions, the enrichment factors for the studied compounds were obtained in the range of 185–240, and the overall recoveries were ranged from 39.1% to 81.5%. The limits of detection were 0.4–1.2 ng g⁻¹ and the relative standard deviations for 20 ng g⁻¹ of the OCPs, varied from 3.2% to 8% (n = 4). Finally, the proposed method has been successfully applied to the analysis of the OCPs in real fish sample, and satisfactory results were obtained.     

Sensitive Quantification of Carboxylic Acid Metabolite of Clopidogrel in Human Plasma by LC with UV Detection

A rapid LC method with UV detection was developed for the quantification of carboxylic acid metabolite of clopidogrel in human plasma. Following a simple protein precipitation using a mixture of methanolic solution of ZnSO₄, the analyte and commercially available internal standard were separated using a mobile phase of water–acetonitril (85:15, v/v) adjusted to pH 3.5 on a Chromolith C18 column at a flow rate of 2.5 mL min^?1 with a total retention time of 4 min. Linearity was verified over the range of 20–3,000 ng mL^?1 where the LOQ was 20 ng mL^?1. This method was applied in a pharmacokinetic study.     

Tuning the primary resonances of a micro resonator,using piezoelectric actuation

Microbeam dynamics is important in MEMS filters and resonators. In this research, the effect of piezoelectric actuation on the resonance frequencies of a piezoelectrically actuated capacitive clamped-clamped microbeam is studied. The microbeam is sandwiched with piezoelectric layers throughout its entire length. The lower piezoelectric layer is exposed to a combination of a DC and a harmonic excitation voltage. The DC electrostatic voltage is applied to prevent the doubling of the excitation frequency. The traditional resonators are tuned using DC electrostatic actuation, which tunes the resonance frequency only in backward direction on the frequency domain. The proposed model enables tuning the resonance frequencies in both forward and backward directions. For small amplitudes of harmonic excitation and high enough quality factor, the frequency response curves obtained by the shooting method are validated with those of the multiple time scales technique. Unlike the perturbation technique, which imposes limitation on both the amplitude of the harmonic excitation and the quality factor to be applicable, the shooting method can be applied to capture the periodic attractors regardless of how big the amplitude of harmonic excitation and the quality factor are.     

Stabilizing the pull-in instability of an electro-statically actuated micro-beam using piezoelectric actuation

In the present article an investigation is presented into the stability of an electro-statically deflected clamped–clamped micro-beam sandwiched by two piezoelectric layers undergoing a parametric excitation applying an AC voltage to these layers. Applying an electrostatic actuation not only deflects the micro-beam but also decreases the bending stiffness of the structure, which can lead the structure to an unstable position by undergoing a saddle node bifurcation. Utilizing an appropriate AC actuation voltage to the piezoelectric layers produces a time varying axial force, which can play the role of a stabilizer exciting the system parameter. The governing equation of the motion is a nonlinear electro-mechanically coupled type PDE, which is derived using variational principle and discretized, applying Eigen-function expansion method. The resultant is a Mathieu type equation in its damped form. Using Floquet theory for single degree of freedom system the stable and unstable regions of the problem are investigated. The effects of viscous damping and electrostatic actuation on the stable regions of the problem are also studied.     

Parametric excitation of a piezoelectrically actuated system near Hopf bifurcation

This paper deals with investigation into the stability analysis for transverse motions of a cantilever micro-beam, which is axially loaded due to a voltage applied to the piezoelectric layers located on the lower and upper surfaces of the micro-beam. The piezoelectric layers are pinned to the open end of the micro-beam and not bonded to it through its length. Application of the DC and AC piezoelectric actuations creates steady and time varying axial forces. The equation of the motion is derived using variational principal, and discretized using modal expansion theorem. The differential equations of the discretized model are a set of Mathieu type ODEs, whose stability analysis is performed using Floquet theory for multiple degree of freedom systems. Considering first two eigen-functions in the modal expansion theorem leads in the prediction of flutter type of instability as a consequence of Hopf bifurcation, which is not seen in the reduced single degree of freedom system. The object of the present study is to passively control the flutter instability in the proposed model by applying AC voltage with suitable amplitude and frequency to the piezoelectric layers. The effect of various parameters on the stability of the structure, including damping coefficient, amplitude of the DC and AC voltages, and the frequency of the applied AC voltage is studied.     

An Electrochemiluminescence Biosensor for the Detection of Alzheimer’s Tau Protein Based on Gold Nanostar Decorated Carbon Nitride Nanosheets

Human Tau protein is the most reliable biomarker for the prediction of Alzheimer’s disease (AD). However, the assay to detect low concentrations of tau protein in serum is a great challenge for the early diagnosis of AD. This paper reports an electrochemiluminescence (ECL) immunosensor for Tau protein in serum samples. Gold nanostars (AuNSs) decorated on carbon nitride nanosheets (AuNS@g-CN nanostructure) show highly strong and stable ECL activity compared to pristine CN nanosheets due to the electrocatalytic and surface plasmon effects of AuNSs. As a result of the strong electromagnetic field at branches, AuNSs showed a better ECL enhancement effect than their spherical counterpart. For the fabrication of a specific immunosensor, immobilized AuNSs were functionalized with a monoclonal antibody specific for Tau protein. In the presence of Tau protein, the ECL intensity of the immunosensor decreased considerably. Under the optimal conditions, this ECL based immunosensor exhibits a dynamic linear range from 0.1 to 100 ng mL⁻¹ with a low limit of detection of 0.034 ng mL⁻¹. The LOD is less than the Tau level in human serum; thus, this study provides a useful method for the determination of Tau. The fabricated ECL immunosensor was successfully applied to the detection of Tau, the biomarker in serum samples. Therefore, the present approach is very promising for application in diagnosing AD within the early stages of the disease.