Neuropharmacokinetic evaluation of lactoferrin-treated indinavir-loaded nanoemulsions: remarkable brain delivery enhancement

Objective: Indinavir (IDV), an antiretroviral protease inhibitor used in treatment of HIV infection, has limited entry into brain due to efflux by the P-glycoprotein presented in blood–brain barrier. The aim of present study was to develop lactoferrin-treated nanoemulsion containing indinavir (Lf-IDV-NEs) for delivery to brain.

Methods: Indinavir-loaded nanoemulsions (IDV-NEs) were prepared by high-speed homogenization method, and then lactoferrin was coupled to IDV-NEs by water soluble EDC method.

Results: The hydrodynamic diameters, polydispersity index, and zeta potential of IDV-NEs were 112?±?3.5?nm, 0.20?±?0.02, and ?33.2?±?2.6?mV, respectively. From in vivo studies in animal model of rats, the AUC_0–4?h of brain concentration–time profile of IDV-NEs and Lf-IDV-NEs were 1.6 and 4.1 times higher than free drug, respectively. The brain uptake clearance of IDV-NEs and Lf-IDV-NEs were, interestingly, 393- and 420-times higher than the free drug.

Conclusions: It can be concluded that applying both lactoferrin-treated and non-treated nanoemulsions clearly leads to significant brain penetration enhancement of indinavir, an effect which is more pronounced in the case of Lf-IDV-NEs with the higher drug residence time in brain.     

Dendrosomes as novel gene porters‐III

BACKGROUND: It was previously reported that dendrosomes, i.e. neutral, biodegradable, covalent or self‐assembled, hyperbranched, spheroidal nano‐particles with a size ranging from 15 to 100 nm, provide a convenient and efficient means of gene delivery into various kinds of cells such as human hepatoma and kidney cells as well as animal models. RESULTS: New studies via circular dichroism show that hydrophilic and amphipathic dendrosomes either do not affect the DNA structure or moderately transform it from B‐ to A‐conformation. Gene delivery into human liver, kidney, and endothelial cells as well as other animal cells like Bowes, U‐937, Raw, CCRF‐CEM, MOLT‐4, K562, Huh‐7 and VERO reveal that the genes are efficiently expressed and in comparison with other gene porters like Lipofectin or bacterial ghosts, do quite well. It is also shown that dendrosomes are able to deliver genes into cells like endothelials that are usually hard to transfect. Cell culture experiments as well as intraperitoneal/intradermal injections of dendrosomes into mice establish their nontoxicity (up to 2.5 mg kg^?1 of animal weight in the latter case). Studies on immunization of BALB/c mice using conventional adjuvants such as aluminium phosphate, C_pG motif and one of the dendrosomes, indicate that the latter leads to the mildest initial response development while exceeding them afterwards. CONCLUSION: CD studies reveal that, owing to the neutrality of dendrosomes, formation of Den/DNA complexes is accompanied by slight structural modifications of DNA cell culture, and animal studies reveal that dendrosomes are inert, non‐toxic and highly efficient gene porters that perform at extremely low doses. In comparison with bacterial ghosts and some common porters, they are efficient in delivery of genes into animals and a variety of cells including those that are usually hard to transfect. Copyright © 2008 Society of Chemical Industry     

Effective moduli and failure considerations for composites with periodic fiber waviness

A finite element micromechanical model for fibrous materials introduced in a previous work [J. Compos. Mater. 38 (4) (2004) 273] is used to further study the effects of periodic and localized fiber waviness. A periodic unit cell based on hexagonal fiber packing and sinusoidal fiber waviness was assumed as a representative volume element. Equivalent to this wavy-shaped unit cell, a straight unit cell but with wavy material-orientation is introduced. This type of homogenized continuum modeling simplifies the analysis since the wavy geometry with details of constituent materials is avoided. Thus, stiffness parameters associated with individual lamina with waviness are estimated when subject to the constraining effects of neighboring isotropic or straight fiber material layers. It is shown that the shear constraint of the added layers increases the effective moduli of the wavy layer by inhibiting the fiber straightening deformation mechanism. The local stress distribution is also examined and the potential for material failure is investigated. The methodology provides a platform to study the behavior of wavy fiber composites in a systematic manner.     

Optimization of energy management and conversion in the water systems based on evolutionary algorithms

Neural Computing and Applications - In this article, an application of weed optimization algorithm (WOA) for reservoir operation was proposed. In addition, genetic algorithm (GA) and particle swarm...     

Neuroimaging computer-aided diagnosis systems for Alzheimer's disease

This paper has reviewed the state-of-the-art approaches for Computer Aided Diagnosis Systems (CADS) for Alzheimer's Disease (AD) using neuroimaging. Identification of the current approaches leads to improving the efficiency of these techniques. The analysis covered 110 articles published between 2009 and January 2018. Papers were chosen according to the Newcastle-Ottawa criteria. MeSH terms were “computer aided diagnosis systems for Alzheimer's disease” and “computer aided diagnosis systems methods for diagnosis of Alzheimer's disease”. CADS algorithms have been presented with specific methods. There is no standardized approach to determine the best one. This study has tables that aimed to conclude all methods in a precise way. Among them, Statistical Parametric Mapping (SPM), Principal Component Analysis (PCA), and Support Vector Machine (SVM) were the most common, respectively. CADS for AD could become important in clinical practice in the near future. The evaluation criteria approved their efficiency as a second opinion besides the neurologist.     

Bis (dibenzylidene acetone) palladium (0) catalyst for glycerol oxidation in half cell and in alkaline direct glycerol fuel cell

In this study, catalytic activity and performance of bis (dibenzylidene acetone) palladium (0) catalyst, Pd (DBA)₂, was evaluated toward glycerol oxidation reaction (GOR) in alkaline half cell and alkaline direct glycerol fuel cell (DGFC). The electrooxidation of glycerol on Pd (DBA)₂ was characterized in half cell by cyclic voltammetry (CV), electrochemical impedance spectroscopy (EIS) and chronoamperometry (CA) techniques. Obtained results have highlighted the excellent electrocatalyst activity of Pd (DBA)₂ in terms of specific peak current density and onset potential compared to the results obtained by conventional Pd base catalysts. CVs results also demonstrate that Pd (DBA)₂ is still active even after 200 cycles.     

Detection of broken rotor bars in induction motors using nonlinear Kalman filters

This paper presents a model-based fault detection approach for induction motors. A new filtering technique using Unscented Kalman Filter (UKF) and Extended Kalman Filter (EKF) is utilized as a state estimation tool for on-line detection of broken bars in induction motors based on rotor parameter value estimation from stator current and voltage processing. The hypothesis on which the detection is based is that the failure events are detected by jumps in the estimated parameter values of the model. Both UKF and EKF are used to estimate the value of rotor resistance. Upon breaking a bar the estimated rotor resistance is increased instantly, thus providing two values of resistance after and before bar breakage. In order to compare the estimation performance of the EKF and UKF, both observers are designed for the same motor model and run with the same covariance matrices under the same conditions. Computer simulations are carried out for a squirrel cage induction motor. The results show the superiority of UKF over EKF in nonlinear system (such as induction motors) as it provides better estimates for rotor fault detection.     

A new model for investigating the flexural vibration of an atomic force microscope cantilever

A new model for the flexural vibration of an atomic force microscope cantilever is proposed, and a closed-form expression is derived. The effects of angle, damping and tip moment of inertia on the resonant frequency were analysed. Because the tip is not exactly located at one end of the cantilever, the cantilever is modelled as two beams. The results show that the frequency first increases with increase in angle and then decreases to a constant value for high values of the angle. Moreover, the damping is increased at lower contact positions. The tip moment of inertia is also sensitive to the resonant frequency at small values for the odd modes and large values for the even modes.