Purpose
This exploration is aimed at developing sorafenib (SF)-loaded cationically-modified polymeric nanoparticles (NPs) as inhalable carriers for improving the therapeutic efficacy of SF against ...non-small cell lung cancer (NSCLC).
Methods
The NPs were prepared using a solvent evaporation technique while incorporating cationic agents. The optimized NPs were characterized by various physicochemical parameters and evaluated for their aerosolization properties. Several
in-vitro
evaluation studies were performed to determine the efficacy of our delivery carriers against NSCLC cells.
Results
Optimized nanoparticles exhibited an entrapment efficiency of ~40%, <200 nm particle size and a narrow poly-dispersity index. Cationically-modified nanoparticles exhibited enhanced cellular internalization and cytotoxicity (~5-fold IC
50
reduction
vs
SF) in various lung cancer cell types. The inhalable nanoparticles displayed efficient aerodynamic properties (MMAD ~ 4 μM and FPF >80%).
In-vitro
evaluation also resulted in a superior ability to inhibit cancer metastasis. 3D-tumor simulation studies further established the anti-cancer efficacy of NPs as compared to just SF.
Conclusion
The localized delivery of SF-loaded nanoparticles resulted in improved anti-tumor activity as compared to SF alone. Therefore, this strategy displays great potential as a novel treatment approach against certain lung cancers.
Several studies have suggested re-evaluation of the wind compensation system (WCS) of the International Ski Federation (FIS). It was introduced in 2009, and since then, the system has been modified ...considerably, but major shortcomings have still remained. The present study compared the effect of tail/head wind on two reference jumps with different aerodynamic properties (Cd and Cl) during the flight phase. Jump distance and total tangential wind speed data of world cup competitions of the season 2020/2021 were used to analyse the FIS WCS and to offer basic information of wind effects. The correlation between the total tangential wind speed and the jump distance varied strongly among the analysed jumping rounds and showed a big variation in the effect of FIS WCS. According to the computer simulation, a steady head/tail wind during the entire flight phase did not show big difference in jump distance between the jumps with different aerodynamic properties. However, wind had a “reverse” effect on the jumps: when applied to the early flight phase, tail wind increased, and head wind decreased the jumping distance. It seems that the favourable wind conditions at the early flight phase may result in an unfair advantage-disadvantage when the current FIS WCS is used. Therefore, based on the present results, the FIS WCS needs to be further discussed and quality of jumpers’ aerodynamic properties re-examined.
The diversity of flying animals suggests that countless combinations of flight morphologies and behaviors have evolved with specific lifestyles, thereby exploiting diverse aerodynamic mechanisms. How ...morphology, flight behavior, and aerodynamic properties together diversify with contrasting ecology remains to be elucidated. We studied the adaptive codivergence in wing shape, flight behavior, and aerodynamic efficiency among
butterflies living in different forest strata by combining high-speed videography in the field with morphometric analyses and aerodynamic modeling. By comparing canopy and understory species, we show that adaptation to an open canopy environment resulted in increased glide efficiency. Moreover, this enhanced glide efficiency was achieved by different canopy species through distinct combinations of flight behavior, wing shape, and aerodynamic mechanisms, highlighting the multiple pathways of adaptive evolution.
High porous particles with specific aerodynamic properties were processed by the spray freeze-drying (SFD) method. Comprehensive knowledge about all aspects of the SFD method is required for particle ...engineering of various pharmaceutical products with good flow properties. In this review, different types of the SFD method, the most frequently employed excipients, properties of particles prepared by this method, and most recent approaches concerning SFD are summarized. Generally, this technique can prepare spherical-shaped particles with a highly porous interior structure, responsible for the very low density of powders. Increasing the solubility of spray freeze-dried formulations achieves the desired efficacy. Also, due to the high efficiency of SFD, by determining the different features of this method and optimizing the process by model-based studies, desirable results for various inhaled products can be achieved and significant progress can be made in the field of pulmonary drug delivery.
The study documents the flower-like lactose particles as potential carriers to improve Dry Powder Inhaler (DPI) efficiency. The lactose particles (LMx, LMf) are prepared by anti-solvent ...crystallization and compared with commercial lactose carriers (Inhalac 251; LMc). Formulations of 1.48% w/w drug loading are prepared using salbutamol sulfate (model drug) and different lactose carriers. The carrier properties are correlated with %FPF using principal component analysis. The analytical results confirm LMx is α-lactose monohydrate, LMf comprises α and β-lactose. Time-resolved crystal growth shows that the LMx particle is agglomerated structure while, LMf particle appear as flower-like structure of size (~45.37–63.92 μm) with high surface and aerodynamic properties compared to LMc. The in-vitro aerosolization studies resulted in higher fine particle fraction (%FPF) for formulations with LMx (~33.23%) and LMf (~44.85%) compared to LMc (~23.40%). The high %FPF is mainly attributed to the higher surface roughness, amorphicity, surface energy of engineered lactose carriers.
Display omitted
•Crystallization induced flower-like lactose gives high %FPF than commercial lactose.•Flower-like lactose particles are potential inhalable carriers for DPI application.•Particle, bulk property and %FPF are correlated using principal component analysis.•High %FPF is due to higher surface roughness, energy and % fine lactose particles.
•A gyroscopic stabilizer is studied to reduce propensity to long-span bridge flutter.•Frequency-domain simulations at incipient aeroelastic instability are performed.•Significant increment of ...critical flutter speed is noticed.
Long-span cable-supported bridges are gaining considerable importance in the world. It is generally recognized that long-span cable-supported bridges can be very sensitive to wind effects due to their aerodynamic properties and deck flexibility. Flutter is usually a major concern because it can lead to structural deck failure. This communication introduces a prototype of gyroscopic device as an active stabilizer for improving flutter performance. A mathematical model of the gyroscopic device, installed at the bridge deck level, was studied and implemented to assess its effectiveness in increasing the critical wind speed. A preliminary study was conducted to evaluate the stabilizer’s performance on a benchmark long-span cable-supported bridge as a function of its gyricity. The results demonstrate that the gyroscopic stabilizer is very successful and bridge flutter threshold increases with the gyricity of the gyroscopic device, within a practical operational range.
This paper investigates the flight dynamics of the aircraft with wing asymmetric damage and the fault-tolerant control problem to improve the stability and flight quality of damaged aircraft. A ...high-fidelity wing asymmetric damaged aircraft nonlinear model is developed, as well as the impact of wing asymmetric damage on the physical and aerodynamic properties of the aircraft is also analyzed. The trim strategies for damaged aircraft are investigated to achieve a rapid estimation of trim states after damage occurs. This paper presents a robust cascaded nonlinear fault-tolerant control framework that integrates the incremental nonlinear dynamic inversion control with improved piecewise-constant-based nonlinear L1 adaptive control for the stability control to enhance the stability and tracking performance of the damaged aircraft. Theoretical analysis proves that the presented fault-control structure is robust to disturbances and can decouple rapidity and robustness while guaranteeing steady-state and transient performance. Finally, the hardware-in-the-loop flight control experiment platform is developed to validate the cascaded nonlinear fault-tolerant controller. In the experiment, the proposed controller is verified under wing asymmetric damage and compared with existing methods. Experimental results show that the proposed fault-tolerant control is able to overcome wing asymmetric damage and significantly improve the tracking performance of the damaged aircraft even with 27.2% of the severe damage to the left-wing.
•A high-fidelity nonlinear aircraft model with wing asymmetric damage is established.•A cascaded nonlinear fault-tolerant flight controller is developed.•Nonlinear L1 adaptive controller with modified piecewise-constant adaptation and incremental nonlinear dynamic inversion.•Analyzes the impact of different degrees of wing asymmetric damage for aircraft.•A series of the flight control hardware-in-the-loop (HIL) platform experiment verification.
The objective of the study was to determine the geometric, gravimetric, aerodynamic, and frictional properties of maize grain as affected by varietal differences and moisture content. Honampa, ...Omankwa, Abontem, Timtim, and Obatanpa were the five maize grain varieties studied. Moisture content, geometric properties, gravimetric properties, aerodynamic properties, and frictional properties were studied. The geometric mean diameters ranged between 6.65 and 7.55 mm, while projected areas ranged between 52.98 and 73.12 m
2
. The surface area was between 139.69 and 180.29 mm
2
, and sphericity was from 0.71 to 0.80. The following ranges were obtained as thousand grain weight (213.74 and 292.89 g), and bulk density (709.50 and 746.00 kg/m
3
). The volume of a single seed was between 1.71 × 10
−7
and 2.34 ×
10−7
m
3
while true density was 1250.0 kg/m
3
. Porosity ranged from 40.32% to 43.24% and terminal velocity ranged between 2.12 and 2.98 m/s. Drag coefficient of 7.18 to 14.60, drag force of 0.002 to 0.003, and Reynolds number between 992.71 and 1579.20 were similarly obtained. The static angle of repose varied with material surfaces while the dynamic angle of repose varied with grain variety. The grain demonstrated 19° static angle of repose, which portrays a very free flow. All the geometric properties increased with moisture besides sphericity although insignificant. The thousand grain weight, volume of single grain, and porosity increased with moisture content. Nonetheless, bulk density decreased and true density remained the same as moisture content increased. Terminal velocity, Reynolds number, and drag force increased as drag coefficient decreased with moisture content. The frictional properties increased with moisture content, and the Reynolds number was <2100, hence, the linear flow of grain. Geometric, gravimetric, aerodynamic, and frictional properties of maize grain were dependent on both grain variety and moisture content.
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