Advanced Drug Delivery Micro- and Nanosystems for Cardiovascular Diseases

Advanced drug delivery micro- and nanosystems have been widely explored due to their appealing specificity/selectivity, biodegradability, biocompatibility, and low toxicity. They can be applied for the targeted delivery of pharmaceuticals, with the benefits of good biocompatibility/stability, non-immunogenicity, large surface area, high drug loading capacity, and low leakage of drugs. Cardiovascular diseases, as one of the primary mortalities cause worldwide with significant impacts on the quality of patients’ life, comprise a variety of heart and circulatory system pathologies, such as peripheral vascular diseases, myocardial infarction, heart failure, and coronary artery diseases. Designing novel micro- and nanosystems with suitable targeting properties and smart release behaviors can help circumvent crucial challenges of the tolerability, low stability, high toxicity, and possible side- and off-target effects of conventional drug delivery routes. To overcome different challenging issues, namely physiological barriers, low efficiency of drugs, and possible adverse side effects, various biomaterials-mediated drug delivery systems have been formulated with reduced toxicity, improved pharmacokinetics, high bioavailability, sustained release behavior, and enhanced therapeutic efficacy for targeted therapy of cardiovascular diseases. Despite the existing drug delivery systems encompassing a variety of biomaterials for treating cardiovascular diseases, the number of formulations currently approved for clinical use is limited due to the regulatory and experimental obstacles. Herein, the most recent advancements in drug delivery micro- and nanosystems designed from different biomaterials for the treatment of cardiovascular diseases are deliberated, with a focus on the important challenges and future perspectives.     

A robust-adaptive fuzzy coverage control for robotic swarms

In this paper, a decentralized adaptive control scheme for multi-robot coverage is proposed. This control method is designed based on centroidal Voronoi configuration integrated with robust adaptive fuzzy control techniques. We consider simple single integrator mobile robots used for covering dynamical environments, where an adaptive fuzzy logic system is used to approximate the unknown parts of control law. A robust coverage criterion is used to attenuate the adaptive fuzzy approximation error and measurement noises to a prescribed level. Therefore, the robots motion is forced to obey solutions of a coverage optimization problem. The advantages of the proposed controller can be listed as robustness to external disturbances, computation uncertainties, and measurement noises, while applicability on dynamical environments. A Lyapunov-function based proof is given of robust stability, i.e. convergence to the optimal positions with bounded error. Finally, simulation results are demonstrated for a swarm coverage problem simultaneous with tracking mobile intruders.     

Flow Around a Crack in a Porous Matrix and Related Problems

The equations governing plane steady-state flow in heterogeneous porous body containing cracks are presented first. Then, a general transformation lemma is presented which allows extending a particular solution obtained for a given flow problem to another configuration with different geometry, behaviour and boundary conditions. An existing potential solution in terms of discharges along the cracks, established by Liolios and Exadaktylos (J Solids Struct 43:3960–3982, 2006) for non-intersecting cracks in isotropic matrix, is extended to intersecting cracks in anisotropic matrix. The basic problem of a single straight crack in an infinite body submitted to a pressure gradient at infinity is then investigated and a closed-form solution is presented for the case of void cracks (infinite conductivity), as well as a semi-analytical solution for the case of cracks with Poiseuille type conductivity. These solutions, derived first for an isotropic matrix, are then extended to anisotropic matrices using the general transformation lemma. Finally, using the solution obtained for a single crack, a closed-form estimation of the effective permeability of micro-cracked porous materials with weak crack density is derived from a self-consistent upscaling scheme.     

Spectrophotometric resolution of ternary mixtures of pseudoephedrine hydrochloride, dextromethorphan hydrobromide, and sodium benzoate in syrups using wavelength selection by net analyte signals calculated with hybrid linear analysis

Hybrid linear analysis (HLA), as a recent factor-based multivariate calibration technique, was applied for the spectrophotometric determination of ternary mixtures of pseudoephedrine hydrochloride (PSU), dextromethorphan hydrobromide (DXT), and sodium benzoate (BNZ). The utilized HLA was assisted by a wavelength selection procedure which was based on the calculation of the net analyte signal (NAS) regression plot in any considered wavelengths window for each test sample, in addition to a moving window strategy for searching the region with maximum linearity of NAS regression plot (minimum error indicator (EI)). HLA was applied because it was simpler to adapt to the NAS regression plot methodology, and also used less factors than partial least squares (PLS). An orthogonal array design was applied for formation of calibration and prediction sets in the concentration ranges 0-7500 μmol L⁻¹ for PSU, 0-300 μmol L⁻¹ for DXT, and 0-1400 μmol L⁻¹ for BNZ. The method had the ability to select wavelength regions that minimize the effect of non-linearity of the spectral data, in addition to that of non-modeled interferences. The application of the selected wavelength regions improved the obtained relative standard error of predictions for PSU, DXT, and BNZ, respectively, from 5.24, 8.67, and 5.48% to 2.19, 5.21, and 3.62% (using lower number of factors). To check the ability of the proposed method in selection of linear regions of spectra, a test for detecting non-linear regions of spectral data in multivariate spectroscopic assays was also described. Additives in the commercial syrup samples did not interfere with their determinations. The method was successfully applied for the determination of pseudoephedrine HCl, dextromethorphan HBr, and sodium benzoate in cough suppressant syrup samples.     

A general solution procedure for vibrations of systems with cubic nonlinearities and nonlinear/time-dependent internal boundary conditions

The subject of this paper is the development of a general solution procedure for the vibrations (primary resonance and nonlinear natural frequency) of systems with cubic nonlinearities, subjected to nonlinear and time-dependent internal boundary conditions—this is a commonly occurring situation in the vibration analysis of continuous systems with intermediate elements. The equations of motion form a set of nonlinear partial differential equations with nonlinear, time-dependent, and coupled internal boundary conditions. The method of multiple timescales, an approximate analytical method, is applied directly to each partial differential equation of motion as well as coupled boundary conditions (i.e. on each sub-domain and the corresponding internal boundary conditions for a continuous system with intermediate elements) which ultimately leads to approximate analytical expressions for the frequency-response relation and nonlinear natural frequencies of the system. These closed-form solutions provide direct insight into the relationship between the system parameters and vibration characteristics of the system. Moreover, the suggested solution procedure is applied to a sample problem which is discussed in detail.     

Design of a fast convergent backpropagation algorithm based on optimal control theory

The main contribution of this paper is using optimal control theory for improving the convergence rate of backpropagation algorithm. In the proposed approach, the learning algorithm of backpropagation is modeled as a minimum time control problem in which the step-size of its learning factor is considered as the input of this model. In contrast to the traditional backpropagation, learning algorithms which select the step-size by trial and error, it is selected adaptively based on optimal control criterion. The effectiveness of the proposed algorithm is evaluated in two simulations: XOR and 3-bit parity. In both simulation examples, the proposed algorithm outperforms well in speed and the ability to escape from local minima.     

Determination of copper,lead, cadmium and zinc content in commercially valuable fish species from the Persian Gulf using derivative potentiometric stripping analysis

This study was performed to determine the concentrations of cadmium, lead, copper and zinc in the edible muscle of pelagic (Scomberomorus commerson, Chirocentrus dorab, Sphyraena jello, Rachycentron conadum, Thunus tonggol, and Tenualosa ilisha) and demersal (Nemipterus japonicas, Epinephelus coioides, Platycephalus indicus, Psettodes erumei, Pomadasys argenteus, and Acanthopagrus latus) fish species from the Persian Gulf during winter and summer. The samples were analyzed by the derivative potentiometric stripping technique; and the results were expressed as μg/g of wet weight. The obtained range of metals in fish species was 0.024–0.111 μg/g for cadmium, 0.057–0.471 μg/g for lead, 0.799–4.790 μg/g for copper and 3.226–11.390 μg/g for zinc. The study revealed that seasonal variation influenced the concentration of metals in the samples. The highest concentration of cadmium, lead, copper and zinc was found in Platycephalus indicus (0.147 μg/g), Acanthopagrus latus (0.534 μg/g), Psettodes erumei (5.294 μg/g) and Psettodes erumei (13.528 μg/g) in winter, respectively. Moreover, demersal fish species had higher cadmium, lead and zinc concentrations, but lower copper content than pelagic ones. Our study demonstrated that the estimated daily and weekly intakes of lead, copper and zinc, and estimated monthly intake of cadmium via consumption of fish flesh were below the PTDI, PTWI and PTMI values established by FAO/WHO.     

Experimental and quantum chemical study on the IR, UV and electrode potential of 6-(2,3-dihydro-1,3-dioxo-2-phenyl-1H-inden-2-yl)-2,3-dihydroxybenzaldehyde

Electrode potential of 6-(2,3-dihydro-1,3-dioxo-2-phenyl-1H-inden-2-yl)-2,3-dihydroxybenzaldehyde (DPDB) in methanol have been calculated theoretically. For the achievement of this task, the density functional theory (B3LYP/6-31G(d)) was employed with the inclusion of the entropic and thermochemical corrections to yield the free energies of the redox reactions. The electrode potential was also obtained experimentally by means of an electrochemical technique (cyclic voltammetry). The geometric parameters, the vibrational frequency values and the UV spectrum of DPDB and 2-(2,3-dihydro-1,3-dioxo-2-phenyl-1H-inden-2-yl)-5,6-dioxocyclohexa-1,3-dienecarbaldehyde (DPDD is the oxidized form of DPDB), were computed using the same methods. The calculated IR spectrum of DPDB, used for the assignment of the IR frequencies, was observed in the experimental FT-IR spectrum. The correlation between the theoretical and experimental DPDB vibrational frequencies was 0.996. This agreement mutually verified the accuracy of the experimental method and the validity of the applied mathematical model.     

Molecular parameterization and determination of the electrode potentials of anticoagulant derivatives: Electrochemical and quantum chemical study

This research presents calculations and computation of two anticoagulant derivatives electrode potentials in methanol. For this purpose, the ab initio molecular orbital calculations (HF) and density functional theory (DFT) together with the 6-31G(d) basis set were utilized. The calculated values were compared with the experimental values obtained by linear sweep voltammetry. The observed and the calculated changes in the reduction potential of the anticoagulant derivatives differed from those of the reference compound (catechol), being less than 20 mV. In this way, a method was provided, by which the reduction potentials of the related molecules could be predicted very accurately. Actually, the resulting data illustrated that the method was likely to be useful for the prediction of biomolecules electrode potentials in different aprotic solvents. The bond lengths, bond angles and dipole moment of the studied compounds were calculated in two different solvents and the solvent effects were discussed.