Nanoparticles in Clinical Trials: Analysis of Clinical Trials,FDA Approvals and Use for COVID-19 Vaccines

Nanoparticles are heterologous small composites that are usually between 1 and 100 nanometers in size. They are applied in many areas of medicine with one of them being drug delivery. Nanoparticles have a number of advantages as drug carriers which include reduced toxic effects, increased bioavailability, and their ability to be modified for specific tissues or cells. Due to the exciting development of nanotechnology concomitant with advances in biotechnology and medicine, the number of clinical trials devoted to nanoparticles for drug delivery is growing rapidly. Some nanoparticles, lipid-based types, in particular, played a crucial role in the developing and manufacturing of the two COVID-19 vaccines—Pfizer and Moderna—that are now being widely used. In this analysis, we provide a quantitative survey of clinical trials using nanoparticles during the period from 2002 to 2021 as well as the recent FDA-approved drugs (since 2016). A total of 486 clinical trials were identified using the clinicaltrials.gov database. The prevailing types of nanoparticles were liposomes (44%) and protein-based formulations (26%) during this period. The most commonly investigated content of the nanoparticles were paclitaxel (23%), metals (11%), doxorubicin (9%), bupivacaine and various vaccines (both were 8%). Among the FDA-approved nanoparticle drugs, polymeric (29%), liposomal (22%) and lipid-based (21%) drugs were the most common. In this analysis, we also discuss the differential development of the diverse groups of nanoparticles and their content, as well as the underlying factors behind the trends.     

Dispirooxindole-β-Lactams: Synthesis via Staudinger Ketene-Imine Cycloaddition and Biological Evaluation

In this work, we present the first synthesis of dispirooxindole-β-lactams employing optimized methodology of one-pot Staudinger ketene-imine cycloaddition with N-aryl-2-oxo-pyrrolidine-3-carboxylic acids as the ketene source. Spiroconjugation of indoline-2-one with β-lactams ring is considered to be able to provide stabilization and wide scope of functionalization to resulting scaffolds. The dispipooxindoles obtained demonstrated medium cytotoxicity in the MTT test on A549, MCF7, HEK293, and VA13 cell lines, and one of the compounds demonstrated antibacterial activity against E. coli strain LPTD.     

Dot Size Thermal Objects Detection in Atmosphere of Infrared Range

The article deals with the experimental studies of atmosphere indistinct radiation structure. The information extraction background of dot size thermal object presence in atmosphere is reasonable. Indistinct generalization of experimental study regularities technique of space-time irregularity radiation structure in infrared wave range is offered. The approach to dot size thermal object detection in atmosphere is proved with a help of threshold method in the thermodynamic and turbulent process conditions, based on the indistinct statement return task solution.     

Robophysical study of excavation in confined environments

Soil-dwelling social insects build complex nests. Nest excavation is performed by multiple animals simultaneously and is governed by local interactions of the workers with other nest-mates and their surroundings. To investigate collective confined excavation challenges, we built groups of robotic excavators capable of performing hours of autonomous tunnel excavation in a model cohesive granular medium. Excavator behavior was governed by a simple set of rules triggered by interactions with the surrounding environment and other robots. The rate of tunnel growth and energetic costs of excavation were measured for groups of different numbers operating in wide and narrow tunnels. To extend the results to systems with large numbers of robots, we developed a cellular automata model. Experiments and simulations showed that in sufficiently wide tunnels an increase in the size of the excavating group increased the excavation rates without a significant increase in the energy consumption per robot. A decrease in the tunnel width resulted in a decrease in the excavation rates and increase in the energetic costs of excavation. We attribute this effect to the emergence of multiple time-consuming interactions (clogs) among excavating robots in the confined spaces. Although in all situations clogs were resolvable, clog resolution took longer in the systems with larger number of robots and narrower tunnels. We expect that our robotic system can be used to investigate the behavior of social insects in confined spaces as well as inspire more sophisticated search-and-rescue robotics.     

On the dynamics and Lyapunov stability of constrained and embedded rigid bodies

Lyapunov stability of constrained and embedded rigid bodies is considered. The constraints are of the equality type where the desired motion is to take place on an a priori defined submanifold of movement. Special and augmented state spaces for the representation of systems of rigid bodies are presented. A systematic method of stabilizing these augmented systems and a procedure for constructing Lyapunov functions are presented. The representation is applicable to augmented as well as reduced state spaces of the system defined by the constraints. The augmented state space results from the embedding of the free rigid body system in the larger state space of free rigid body and position control states, and in which the Lyapunov function is constructed. The reduced state space results when the system is restricted and is reduced to lie on the submanifold of movement. It is shown that, for the class of rigid bodies and the physical constraints considered, the projected feedback structures, and the reduced Lyapunov function constitute appropriate stabilizing structures for the constrained system. It is shown that the method applies equally to holonomically constrained and visco-elastically coupled rigid bodies. Digital computer simulations of one single rigid body system are presented to demonstrate the feasibility and effectiveness of the method. Applications to natural systems and the role of cartilage, ligaments and muscles in maintaining the integrity and stability of the joints are noted.     

Comparing Five and Lower-Dimensional Grain Boundary Character and Energy Distributions in Copper: Experiment and Molecular Statics Simulation

Metallurgical and Materials Transactions A - The misorientation of 515 grain boundaries has been determined using electron backscatter diffraction data from an 18 μm thick copper foil with...     

The Effect of Titanium, Zirconium and Tin on the Growth of Diatom Synedra Acus and Morphology of Its Silica Valves

The effect of three Group IV metals (titanium, zirconium and tin) on the growth, morphology and chemical composition of the freshwater diatom Synedra acus subsp. radians (Kützing) Skabichevsky was studied and compared with germanium. The elements in their highest oxidation states were introduced into the culture medium in the form of hydroxides. Germanium was found to be toxic at ??5?mol. % of the total Ge-Si content in the culture medium. In the presence of other elements, a slight decrease in the cell division rate was observed independent of the element within 1?C15% content interval. The analysis of the obtained biomass and silica valves revealed the presence of all the added elements within the cells. However, only germanium was incorporated into the valves in considerable amounts. S. acus cultivation with the addition of 5% Group IV elements resulted in cells having the following aberrations in the structure of the silica valves: changes in valve shape, thickening of valves, alterations of the areolae rows, irregularity or absence of the areolae and a decrease in the mechanical strength of valves. Moreover, the effect of Group IV elements on silica formation was simulated in vitro using a synthetic polymer bearing polyamine and phosphate groups found in silaffines (proteins from diatom frustules). The studied elements were observed to provoke the formation of unstable silica particles in solution. We propose that the observed effects of germanium, titanium, zirconium and tin on diatom growth and structure are due to uncontrollable silica condensation.     

Decomposed control design for non-stationary plants subject to disturbances

This paper combines the block (Luk'yanov and Utkin 1982, 1998), sliding mode and high gain control techniques (Utkin 1992) to form a new decomposed control law suitable for general multivariable non-stationary plants. Different versions of the control law are developed with various dependencies on plant parameters and state variables. The new control law is demonstrated by simulation of its application to an electrical drive employing a dc motor with controlled flux.     

Deformation Control During Thermal Treatment of Electrospun PbZr0.52Ti0.48O3 Nanofiber Mats

This paper focuses on the deformation origin of PbZr_0.52Ti_0.48O₃ (PZT) fiber mats obtained by electrospinning. The main cause of deformation of the green mats during heating was found to be a nonuniform relaxation of the stretched PVP polymer, due to nonuniform thermal decomposition of the Pb‐hexanoate in the fibers. This relaxation starts under 100°C, well below the polymer decomposition temperature. The shrinkage was found to accelerate above the polymer glass transition point, giving rise to an overall linear change of almost 50%. The “green” PZT mats were easily separated from the collector by first depositing a pure PVP sublayer on the collector. An optimal fabrication and slow multistep thermal treatment process that provides fiber mats with desired PZT phase and overcomes the nonuniform deformation is described.