Investigation of the size and shape of nano-microcarriers for targeted drug delivery to atherosclerotic plaque in ischemic stroke prevention.

Recognizing the significance of drug carriers in the treatment of atherosclerotic plaque is crucial in light of the worldwide repercussions of ischemic stroke. Conservative methodologies, specifically targeted drug delivery, present encouraging substitutes that mitigate the hazards linked to invasive procedures. With the intention of illuminating their considerable significance and prospective benefits, this study examines the impact of the geometry and dimensions of drug-loaded nano-microcarriers on atherosclerotic plaque. The research utilizes a finite element approach to simulate the motion and fluid dynamics of nano-microcarriers loaded with drugs within the carotid arteries. Carriers are available in a variety of shapes and sizes to accommodate patient-specific geometries, pulsatile fluid flow, and non-Newtonian blood properties. Optimization of drug delivery is achieved through the examination of carrier interaction with the inner wall. The results demonstrated that the interaction data between particles and the inner wall of atherosclerotic plaques exhibits micro- and nanoscale patterns that are distinct. Symmetric plaques demonstrate that nanoparticles with a 0.4 shape factor and diameters below 200 nm show the highest interaction rate. Conversely, larger particles (200 and 500 nm) with shape factors of 1 demonstrate comparatively elevated interaction rates. The optimal shape factor for drug-loaded microparticles has been determined to be one, and the number of interactions increases as the diameter of the nanoparticles increases, with a significant increase observed at a shape factor of one. Asymmetric plaques exhibit the maximum interaction rates among particles that have a shape factor of 0.4 and have diameters smaller than 500 µm. The findings establish a foundation for novel therapeutic strategies, establishing nano-microparticles as auspicious contenders for accurate and efficacious drug delivery systems that inhibit plaque proliferation.

Spreading Behavior of Non-Spherical Particles with Reconstructed Shapes Using Discrete Element Method in Additive Manufacturing.

The spreading behavior of particles has a significant impact on the processing quality of additive manufacturing. Compared with spherical metal material, polymer particles are usually non-spherical in shape. However, the effects of particle shape and underlying mechanisms remain unclear. Here, the spreading process of particles with reconstructed shapes (non-spherical particles decomposed into several spherical shapes by stereo-lithography models) are simulated by integrating spherical particles with the discrete element method. The results show that more cavities form in the spreading beds of particles with reconstructed shapes than those of spheres with blade spreading. Correspondingly, particles with reconstructed shapes have lower packing densities, leading to more uniform packing patterns. Slow propagation speeds of velocity and angular velocity lead to "right-upwards" turning boundaries for particles with reconstructed shapes and "right-downwards" turning boundaries for spherical particles. Moreover, as the blade velocity increases, the packing density decreases. Our calculation results verify each other and are in good agreement with the experiment, providing more details of the behavior of non-spherical particles before additive manufacturing. The comprehensive comparison between polymer non-spherical particles and spherical particles helps develop a reasonable map for the appropriate choice of operating parameters in real processes.

Preparation of Non-Spherical Janus Particles via an Orthogonal Dissolution Approach.

Post-synthesis modifications are valuable tools to alter functionalities and induce morphology changes in colloidal particles. Non-spherical polymer particles with Janus characteristics are prepared by combining seeded growth polymerization and selective dissolution. First, spherical polystyrene (PS) particles have been swollen with methyl methacrylate (MMA) with an activated swelling method. This is followed by polymerization that led to particles with two well-separated faces: one made of PS and the second of polymethyl methacrylate (PMMA). Subsequently, non-spherical particles are obtained by exposing the Janus colloids to various solvents. Using the two polymers' orthogonal solubility, solvents are identified to selectively dissolve only one face, leading to hemispherical PS or PMMA particles. It is further investigated how changing the composition of the PMMA face - by either co-polymerization with glycidyl methacrylate or by adding a cross-linker - affects the particles' morphology. The poly-methacrylate face can gain total or partial resistance towards the solvents, resulting in intriguing shapes, such as mushroom-like and Janus dimpled particles. The dissolution mechanisms are investigated via optical microscopy, where total or partial dissolutions can be directly observed. Lastly, prematurely quenching the dissolution of the particle's lobes with water can be used to control the Janus mushroom-like particle aspect ratio.

Non-spherical drug particle deposition in human airway using computational fluid dynamics and discrete element method.

Currently, the air pollution and the respiratory disease problems that affect human health are increasing rapidly. Hence, there is attention for trend prediction of the located deposition of inhaled particles. In this study, Weibel's based human airway model (G0-G5) was employed. The computational fluid dynamics and discrete element method (CFD-DEM) simulation was successfully validated by comparison to the previous research studies. The CFD-DEM achieves a better balance between numerical accuracy and computational requirement when comparing with the other methods. Then, the model was used to analyze the non-spherical drug transport with different drug particle sizes, shapes, density, and concentrations. The results found that all the studied factors affected the drug deposition and particle out-mass percentage except the drug concentration. The drug deposition was increased with the increasing of particle size and particle density due to the influence of particle inertia. The Tomahawk-shaped drug deposited easier than the cylindrical drug shape because of the different drag behavior. For the effect of airway geometries, G0 was the maximum deposited zone and G3 was the minimum deposited zone. The boundary layer was found around bifurcation due to the shear force at the wall. Finally, the knowledge can give an essential recommendation for curing patients with pharmaceutical aerosol. The design suggestion of a proper drug delivery device can be summarized.

A new model for the terminal settling velocity of microplastics.

Microplastic (MP) settling process is important for the transport of microplastic particles (MPs, <5 mm) in water bodies. However, for the control parameter of the drag coefficient (Cd), no generalized formula has been proposed for MPs of different shapes and materials. In this study, a total of 1343 MP settling data were collected from the literature. It was found that the drag law for perfect spheres cannot reasonably predict Cd for MPs with particle Reynolds number of 1-103. A new formula for Cd was developed by introducing the dimensionless particle diameter (d⁎) and two shape descriptors. The absolute error of the new formula is 15.2%, smaller than those (42.5-72.8%) of other existing formulas. Moreover, an explicit model was developed for MP settling velocity by correlating Cd, d⁎, and shape descriptors, with lower absolute error (8.8%) than those (15.4-77.2%) of existing models.

Polymer Colloids: Moving beyond Spherical Particles.

When thinking about colloidal particles, the fist image that comes into mind is that of tiny little polystyrene spheres with a narrow size distribution. While spherical polymer colloids are one of the workhorses of colloid science, scientists have been working on the development of progressively advanced strategies to move beyond particles with spherical shapes, and prepared polymer colloids with more complex morphologies. This short review aims at providing a summary of these developments, focusing primarily on methods applicable to submicron particles, with an eye towards their applications and some discussion about advantages and drawbacks of the various approaches.

Advances in design and applications of polymer brush modified anisotropic particles.

Current advancements in the creation of anisotropy in particles and their surface modification with polymer brushes have established a new class of hybrid materials termed polymer brush modified anisotropic particles (PBMAP). PBMAPs display unique property combinations, e.g., multi-functionality in multiple directions along with smart behavior, which is not easily achievable in traditional hybrid materials. Typically, anisotropic particles can be categorized based on three different factors, such as shape anisotropy (geometry driven), compositional anisotropy (functionality driven), and surface anisotropy (spatio-selective surface modification driven). In this review, we have particularly focused on the synthetic strategies to construct the various type of PBMAPs based on inorganic or organic core which may or may not be isotropic in nature, and their applications in various fields ranging from drug delivery to catalysis. In addition, superior performances and fascinating properties of PBMAPs over their isotropic analogues are also highlighted. A brief overview of their future developments and associated challenges have been discussed at the end.

Porous Structure of Cylindrical Particle Compacts.

The porous compacts of non-spherical particles are frequently used in energy storage devices and other advanced applications. In the present work, the microstructures of compacts of monodisperse cylindrical particles are investigated. The cylindrical particles with various aspect ratios are generated using superquadrics, and the discrete element method was adopted to simulate the compacts formed under gravity deposition of randomly oriented particles. The Voronoi tessellation is then used to quantify the porous microstructure of compacts. With one exception, the median reduced free volume of Voronoi cells increases, and the median local packing density decreases for compacts composed of cylinders with a high aspect ratio, indicating a loose packing of long cylinders due to their mechanical interlocking during compaction. The obtained data are needed for further optimization of compact porous microstructure to improve the transport properties of compacts of non-spherical particles.

A new model for settling velocity of non-spherical particles.

The settlement of non-spherical particles, such as propagules of plants and natural sediments, is commonly observed in riverine ecosystems. The settling process is influenced by both particle properties (size, density, and shape) and fluid properties (density and viscosity). Therefore, the drag law of non-spherical particles is a function of both particle Reynolds number and particle shape. Herein, a total of 828 settling data are collected from the literatures, which cover a wide range of particle Reynolds number (0.008-10000). To characterize the influence of particle shapes, sphericity is adopted as the general shape factor, which varies from 0.421 to 1.0. By comparing the measured drag with the standard drag curve of spheres, we modify the spherical drag law with three shape-dependent functions to develop a new drag law for non-spherical particles. Combined with an iterative procedure, a new model is thus obtained to predict the settling velocity of non-spherical particles of various shapes and materials. Further applications in hydrochorous propagule dispersal and sediment transport are projected based on deeper understanding of the settling process.

Transport of Non-Spherical Particles in Square Microchannel Flows: A Review.

Understanding the behavior of a single particle flowing in a microchannel is a necessary step in designing and optimizing efficient microfluidic devices for the separation, concentration, counting, detecting, sorting, or mixing of particles in suspension. Although the inertial migration of spherical particles has been deeply investigated in the last two decades, most of the targeted applications involve shaped particles whose behavior in microflows is still far from being completely understood. While traveling in a channel, a particle both rotates and translates: it translates in the streamwise direction driven by the fluid flow but also in the cross-section perpendicular to the streamwise direction due to inertial effects. In addition, particles' rotation and translation motions are coupled. Most of the existing works investigating the transport of particles in microchannels decouple their rotational and lateral migration behaviors: particle rotation is mainly studied in simple shear flows, whereas lateral migration is neglected, and studies on lateral migration mostly focus on spherical particles whose rotational behavior is simple. The aim of this review is to provide a summary of the different works existing in the literature on the inertial migration and the rotational behavior of non-spherical particles with a focus and discussion on the remaining scientific challenges in this field.

Polymeric non-spherical coarse microparticles fabricated by double emulsion-solvent evaporation for simvastatin delivery.

Polymeric particles with non-spherical shape or coarse surface have distinct advantages for drug delivery, tissue regeneration and immunomodulation respectively, but it is not easy to control polymeric microparticles in required geometry and surface texture simultaneously. In this study, polymeric non-spherical microparticles with coarse surface were successfully prepared by double emulsion-solvent evaporation technique in the presence of ammonium bicarbonate and the formation mechanism was proposed. In addition, simvastatin was encapsulated in poly[lactic-co-(glycolic acid)] (PLGA) non-spherical microparticles with coarse surface by the same technique and the release kinetics in vitro was fitted as well, which not only enrich the encapsulation techniques of liposoluble drugs in polymeric non-spherical carriers but also envision the potential application for alveolar ridge preservation with local delivery of simvastatin.

Importance of aerosol non-sphericity in estimating aerosol radiative forcing in Indo-Gangetic Basin.

Aerosols are usually presumed spherical in shape while estimating the direct radiative forcing (DRF) using observations or in the models. In the Indo-Gangetic Basin (IGB), a regional aerosol hotspot where dust is a major aerosol species and has been observed to be non-spherical in shape, it is important to test the validity of this assumption. We address this issue using measured chemical composition at megacity Delhi, a representative site of the western IGB. Based on the observation, we choose three non-spherical shapes - spheroid, cylinder and chebyshev, and compute their optical properties. Non-spherical dust enhances aerosol extinction coefficient (ßext) and single scattering albedo (SSA) at visible wavelengths by >0.05km-1 and >0.04 respectively, while it decreases asymmetry parameter (g) by ~0.1. Accounting non-sphericity leads top-of-the-atmosphere (TOA) dust DRF to more cooling due to enhanced backscattering and increases surface dimming due to enhanced ßext. Outgoing shortwave flux at TOA increases by up to 3.3% for composite aerosols with non-spherical dust externally mixed with other spherical species. Our results show that while non-sphericity needs to be accounted for, choice of shape may not be important in estimating aerosol DRF in the IGB.

Influence of particle size, an elongated particle geometry, and adjuvants on dendritic cell activation.

Modern subunit vaccines have many benefits compared to live vaccines such as convenient and competitive large scale production, better reproducibility and safety. However, the poor immunogenicity of subunit vaccines usually requires the addition of potent adjuvants or drug delivery vehicles. Accordingly, researchers are investigating different adjuvants and particulate vaccine delivery vehicles to boost the immunogenicity of subunit vaccines. Despite the rapidly growing knowledge in this field, a comparison of different adjuvants is sparsely found. Until today, little is known about efficient combinations of the different adjuvants and particulate vaccine delivery vehicles. In this study we compared three adjuvants with respect to their immune stimulatory potential and combined them with different particulate vaccine delivery vehicles. For this reason, we investigated two types of polyI:C and a CL264 base analogue and combined these adjuvants with differently sized and shaped particulate vaccine delivery vehicles. A high molecular weight polyI:C combined with a spherical nano-sized particulate vaccine delivery vehicle promoted the strongest dendritic cells activation.

Macrophage uptake of cylindrical microparticles investigated with correlative microscopy.

Cylindrical particles offer the opportunity to develop controlled and sustained release systems for the respiratory tract. One reason is that macrophages can phagocyte such particles only from either of the two ends. We investigated the uptake behaviour of murine alveolar macrophages incubated with elongated submicron-structured particles. For that purpose, fluorescent model silica nanoparticles were interconnected with the biocompatible polysaccharide agarose, building up cylindrical particles within the pores of track-etched membranes. In contrast to common approaches we determined the uptake at different time points with scanning electron microscopy, fluorescence microscopy, and the combination of both techniques - correlative microscopy (CLEM). As a consequence, we could securely identify uptake events and observe in detail the engulfment of particles and confirm, that phagocytosis could only be observed from the tips of the cylinders. CLEM allowed a comparison of the uptake measured with different techniques at identical macrophages. Qualitative and quantitative evaluation of this cylindrical particle uptake showed substantial differences between fluorescence microscopy, electron microscopy and the combination of both (CLEM) within 24h.

Getting in shape: molten wax drop deformation and solidification at an immiscible liquid interface.

The controlled production of non-spherical shaped particles is important for many applications such as food processing, consumer goods, adsorbents, drug delivery, and optical sensing. In this paper, we investigated the deformation and simultaneous solidification of millimeter size molten wax drops as they impacted an immiscible liquid interface of higher density. By varying initial temperature and viscoelasticity of the molten drop, drop size, impact velocity, viscosity and temperature of the bath fluid, and the interfacial tension between the molten wax and bath fluid, spherical molten wax drops impinged on a cooling water bath and were arrested into non-spherical solidified particles in the form of ellipsoid, mushroom, disc, and flake-like shapes. We constructed cursory phase diagrams for the various particle shapes generated over a range of Weber, Capillary, Reynolds, and Stefan numbers, governed by the interfacial, inertial, viscous, and thermal effects. We solved a simplified heat transfer problem to estimate the time required to initiate the solidification at the interface of a spherical molten wax droplet and cooling aqueous bath after impact. By correlating this time with the molten wax drop deformation history captured from high speed imaging experiments, we elucidate the delicate balance of interfacial, inertial, viscous, and thermal forces that determine the final morphology of wax particles.

Non-spherical micro- and nanoparticles: fabrication, characterization and drug delivery applications.

INTRODUCTION: Micro- and nanoparticles in drug and vaccine delivery have opened up new possibilities in pharmaceutics. In the past, researchers focused mainly on particle size, surface chemistry and the use of various materials to control particle characteristics and functions. Lately, shape has been acknowledged as an important design parameter having an impact on the interaction with biological systems. AREAS COVERED: In this review, we report on the latest developments in fabrication methods to tailor particle geometry, summarize analytical techniques for non-spherical particles and highlight the most important findings regarding their interaction with biological systems and their potential applications in drug delivery. EXPERT OPINION: The impact of shape on particle internalization into different cell types and particle biodistribution has been extensively studied in the past. Current research focuses on shape-dependent uptake mechanisms and applications for tumour therapy and vaccination. Different fabrication methods can be used to produce a variety of different particle types and shapes. Key challenges will be the transfer of new non-spherical particle fabrication methods from lab-scale to industrial large-scale production. Not all techniques may be scalable for the production of high quantities of particles. It will also be challenging to transfer the promising in vitro findings to suitable in vivo models.

Influence of particle geometry and PEGylation on phagocytosis of particulate carriers.

Particle geometry of micro- and nanoparticles has been identified as an important design parameter to influence the interaction with cells such as macrophages. A head to head comparison of elongated, non-spherical and spherical micro- and nanoparticles with and without PEGylation was carried out to benchmark two phagocytosis inhibiting techniques. J774.A1 macrophages were incubated with fluorescently labeled PLGA micro- and nanoparticles and analyzed by confocal laser scanning microscope (CLSM) and flow cytometry (FACS). Particle uptake into macrophages was significantly reduced upon PEGylation or elongated particle geometry. A combination of both, an elongated shape and PEGylation, had the strongest phagocytosis inhibiting effect for nanoparticles.

Application of different analytical methods for the characterization of non-spherical micro- and nanoparticles.

Non-spherical micro- and nanoparticles have recently gained considerable attention due to their surprisingly different interaction with biological systems compared to their spherical counterparts, opening new opportunities for drug delivery and vaccination. Up till now, electron microscopy is the only method to quantitatively identify the critical quality attributes (CQAs) of non-spherical particles produced by film-stretching; namely size, morphology and the quality of non-spherical particles (degree of contamination with spherical ones). However, electron microscopy requires expensive instrumentation, demanding sample preparation and non-trivial image analysis. To circumvent these drawbacks, the ability of different particle analysis methods to quantitatively identify the CQA of spherical and non-spherical poly(1-phenylethene-1,2-diyl (polystyrene) particles over a wide size range (40 nm, 2 µm and 10 µm) was investigated. To this end, light obscuration, image-based analysis methods (Microflow imaging, MFI, and Vi-Cell XR Coulter Counter) and flow cytometry were used to study particles in the micron range, while asymmetric flow field fractionation (AF4) coupled to multi-angle laser scattering (MALS) and quasi elastic light scattering (QELS) was used for particles in the nanometer range, and all measurements were benchmarked against electron microscopy. Results show that MFI can reliably identify particle size and aspect ratios of the 10 µm particles, but not the 2 µm ones. Meanwhile, flow cytometry was able to differentiate between spherical and non-spherical 10 or 2 µm particles, and determine the amount of impurities in the sample. As for the nanoparticles, AF4 coupled to MALS and QELS allowed the measurement of the geometric (rg) and hydrodynamic (rh) radii of the particles, as well as their shape factors (rg/rh), confirming their morphology. While this study shows the utility of MFI, flow cytometry and AF4 for quantitative evaluation of the CQA of non-spherical particles over a wide size range, the limitations of the methods are discussed. The use of orthogonal characterization methods can provide a complete picture about the CQA of non-spherical particles over a wide size range.