Study on Confined Impinging Jet Mixer and Mechanism of Flash Nanoprecipitation

Nanoparticles have been given considerable attention and applied in many fields because of their properties that are superior to and more distinct than those of conventional materials. In practice, a stable and reproducible manufacturing process is highly desirable. This review presents the flash nanoprecipitation, a new technique that can rapidly produce nanoparticles. Moreover, the mixing process, the mechanism of particle formation, and the mixer design are discussed.Furthermore, the factors controlling the size stability of the produced nanoparticles are summarised in this review.

Template-free nanostructured particle growth via a one-pot continuous gradient nanoprecipitation

Engineered nanoparticles have emerged as new types of materials for a wide range of applications from therapeutics to energy.Still,fabricating nanomaterials presenting complex inner morphologies and shapes in a simple manner remains a great challenge.Herein,we report the template-free one-pot continuous gradient nanoprecipitation of different types of non-compatible polymers to spontaneously form nanostructured particles.The continuous addition of antisolvent induces precipitation and(re)organization of polymer chains at the forming particle interface,ultimately and naturally developing complex inner morphologies and shapes while particle grows.This low-energy-cost bottom-up assembly approach applies to various functional polymers,possibly embedded with metal nanoparticles,for continuous growth into well-organized nanoparticles.UV crosslinking of the particles and core removal allows both confirming the building process and leading to hollow or multivoid nanomaterials.

Achieving high strength in laser powder-bed fusion processed AlFeCuZr alloy via dual-nanoprecipitations and grain boundary segregation

Additive manufacturing of aluminum alloys has received significant attention in the aerospace industry;however,achieving sufficient high strength,especially at elevated temperatures,remains challenging.Here,a crack-free and near-full dense Al-1Fe-0.6Cu-1.3Zr alloy was fabricated by the laser powder bed fusion(LPBF)technique.The Al-Fe-Cu-Zr alloy exhibits heterogeneous microstructures with two distinct zones.One is the so-called coarse-grain zones(CGZs)with an average grain size of 0.95μm,where(Al,Cu)Fe_(3) nanoparticles precipitate in the Al matrix and Fe and Cu cosegregate at the grain boundaries(GBs).The other is fine-grain zones(FGZs)with an average grain size of 0.45μm,where an Al 3 Zr nanoparti-cle precipitates in each of theα-Al grains(serves as the nuclei),and Fe-rich nanoprecipitates and Fe/Cu cosegregation appear at the GBs.As a result,the LPBF Al-Fe-Cu-Zr alloy,with these unique heteroge-neous structures,displays high strength at both room temperature and elevated temperatures,e.g.,with high yield strengths of 500 MPa at room temperature,and 163 MPa at 573 K,both are higher than those of additive manufactured Al-based alloys reported thus far.It is suggested that the high strength over a wide temperature range of the current LPBF Al alloy is mainly attributed to the combination of the precipitation strengthening mechanism and grain-boundary strengthening mechanism.

Development of a concentration-controlled sequential nanoprecipitation for making lipid nanoparticles with high drug loading

Lipid-based nanostructures have garnered considerable interests over the last two decades,and have achieved tremendous clinical success including thefirst clinical approval of a liposome(Doxil)for cancer therapy in 1995 and the recent COVID-19 mRNA lipid nanoparticle vaccines.Compared to liposomes which have a lipid bilayer surrounding an aqueous core,lipid nanoparticles with a particle structure have several attractive advantages for encapsulating poorly water-soluble drugs such as better stability due to the particle structure,high drug encapsulation efficiency because of a pre-or co-drug-loading strategy.While many studies have reported the synthesis of lipid nanoparticles for hydrophobic drug encapsulation,the pre-cise control of drug loading and encapsulation efficiency remains a significant challenge.This work reports a new concentration-controlled nanoprecipitation plat-form technology for fabricating lipid nanoparticles with tunable drug loading up to 70 wt%.This method is applicable for encapsulating a wide range of drugs from very hydrophobic to slightly hydrophilic.Using this facile method,nanoparticles with tunable drug loading exhibited excellent properties such as small particle size,narrow size distribution,good particle stability,showing great promise for future drug delivery applications.

Phase separation-induced nanoprecipitation for making polymer nanoparticles with high drug loading Special Collection:Distinguished Australian Researchers

Increasing drug loading remains a critical challenge in the development and translation of nanomedicine.High drug-loading nanoparticles have demonstrated unique advantages such as less carrier material used,better-controlled drug release,and improved efficacy and safety.Herein,we report a simple and efficient salt concentration screening method for making polymer nanoparticles with exceptionally high drug loading(up to 66.5 wt%)based on phase separation-induced nanoprecipitation.Upon addition of salt,phase separation occurs in a miscible solvent-water solution delaying the precipitation time of drugs and polymers to different extents,facilitating their co-precipitation thus the formation of high drug-loading nanoparticles with high encapsulation efficiency(>90%)and excellent stability(>1 month).This technology is versatile and easy to be adapted to various hydrophobic drugs,different polymers,and solvents.This salt-induced nanoprecipitation strategy offers a novel approach to fabricating polymer nanoparticles with tunable drug loading,and opens great potentials for future nanomedicines.

Application of flash nanoprecipitation to fabricate poorly water-soluble drug nanoparticles

Nanoparticles are considered to be a powerful approach for the delivery of poorly watersoluble drugs. One of the main challenges is developing an appropriate method for preparation of drug nanoparticles. As a simple, rapid and scalable method, the flash nanoprecipitation(FNP) has been widely used to fabricate these drug nanoparticles, including pure drug nanocrystals, polymeric micelles,polymeric nanoparticles, solid lipid nanoparticles, and polyelectrolyte complexes. This review introduces the application of FNP to produce poorly water-soluble drug nanoparticles by controllable mixing devices, such as confined impinging jets mixer(CIJM), multi-inlet vortex mixer(MIVM) and many other microfluidic mixer systems. The formation mechanisms and processes of drug nanoparticles by FNP are described in detail. Then, the controlling of supersaturation level and mixing rate during the FNP process to tailor the ultrafine drug nanoparticles as well as the influence of drugs, solvent, anti-solvent, stabilizers and temperature on the fabrication are discussed. The ultrafine and uniform nanoparticles of poorly watersoluble drug nanoparticles prepared by CIJM, MIVM and microfluidic mixer systems are reviewed briefly. We believe that the application of microfluidic mixing devices in laboratory with continuous process control and good reproducibility will be benefit for industrial formulation scale-up.

Ultrastrong steel via minimal lattice misfit and high-density nanoprecipitation

Subject Code:E01 With the support from the National Natural Science Foundation of China,significant progress has been made in developing maraging steels with high performances by the research group led by Prof.LV Zhaoping(吕昭平)from the State Key Laboratory for Advanced Metals and Materials,University

Preparation of carbon nitride nanoparticles by nanoprecipitation method with high yield and enhanced photocatalytic activity

As an emerging 2D conjugated material,graphitic carbon nitride(CN) has attracted great research attention as important catalytic medium for transforming solar energy.Nanostructure modulation of CN is an effective way to improve catalytic activities and has been extensively investigated,but remains challenging due to complex processes,time consuming or low yield.Here,taking advantage of recent discovered good solvents for CN,a nanoprecipitation approach using poor solvents is proposed for preparation of CN nanoparticles(CN NPs).With simple processes of CN dissolution and precipitation,we can quickly synthesize CN NPs(^40 nm) with a yield of up to 50%,the highest one to the best of our knowledge.As an example of potential applications,the as-prepared CN NPs were applied to photocatalytic degradation of dyes with an evident boosted performance up to 2.5 times.This work would open a new way for batch preparation of nanostructured CN and pave its large-scale industrial applications.

Realizing high thermoelectric performance of Cu and Ce co-doped p-type polycrystalline SnSe via inducing nanoprecipitation arrays

Thermoelectric(TE)performance of polycrystalline stannous selenide(SnSe)has been remarkably promoted by the strategies of energy band,defect engineering,etc.However,due to the intrinsic insufficiencies of phonon scattering and carrier concentration,it is hard to simultaneously realize the regulations of electrical and thermal transport properties by one simple approach.Herein,we develop Cu and Ce co-doping strategy that can not only greatly reduce lattice thermal conductivity but also improve the electrical transport properties.In this strategy,the incorporated Cu and Ce atoms could induce high-density SnSe_(2) nanoprecipitation arrays on the surface of SnSe microplate,and produce dopant atom point defects and dislocations in its interior,which form multi-scale phonon scattering synergy,thereby presenting an ultralow thermal conductivity of 0.275 W·m^(−1)·K^(−1) at 786 K.Meanwhile,density functional theory(DFT)calculations,carrier concentration,and mobility testing reveal that more extra hole carriers and lower conducting carrier scattering generate after Cu and Ce co-doping,thereby improving the electrical conductivity.The co-doped Sn_(0.98)Cu_(0.01)Ce_(0.01)Se bulk exhibits an excellent ZT value up to~1.2 at 786 K and a high average ZT value of 0.67 from 300 to 786 K.This work provides a simple and convenient strategy of enhancing the TE performance of polycrystalline SnSe.

Engineering photo-controllable fragrance release with flash nanoprecipitation

Controllable profragrance nanoparticles are in great demand for long-lasting scent in flavor and fragrance industries.However,the practical applications of controllable fragrance release are limited by the non-tunable size,structural heterogeneity and poor reproducibility.Herein,a coumarin-derived phototrigger(CM-OH)is covalently conjugated with alcohol fragrances to obtain the corresponding profragrances(CM-R)which enable to release fragrances under the light controlling conditions.Furthermore,we introduce a new engineering strategy to construct fine tunable and highly uniform profragrance nanoparticles with flash nanoprecipitation(FNP)technology,which features commercial available amphiphilic pluronic F127 polymers by encapsulation of photoactivatable profragrances CM-R in hydrophobic cores to enhance the long-lasting photo-controllable fragrance release.With the assistance of FNP technology,amphiphilic pluronic polymer and profragrances CM-R in organic solution are instantaneously mixed and subsequently precipitated in the multi-inlet vortex mixer(MIVM),thus obtaining the pluronic F127-encapsulated profragrance nanoparticles with good homogeneity.Compared to the traditional thermodynamic encapsulation method,the novel kinetic FNP technology can not only tune the size of profragrance nanoparticles with narrow distribution,but also distinctly improve the batch-to-batch reproducibility,which affords an alternative method for scale-up preparation of amphiphilic profragrance nanoparticles in precisely controllable fragrance delivery system.

Polymeric assembled nanoparticles through kinetic stabilization by confined impingement jets dilution mixer for fluorescence switching imaging

Traditional fluorescence switching molecules achieving the state change between on and off states commonly based on UV irradiation. However, it is worth noting that UV irradiation is harmful to both the cancer cells and the normal cells. To achieve fluorescence switching under visible wavelength and avoid complicate molecular design, a fluorophore of 2,4,5,6-tetrakis(carbazol-9-yl)-1,3-dicyanobenzene(4Cz IPN) and a quencher of diarylethene(DAE) were physically incorporated within the biocompatible block copolymer poly(lactic-co-glycolic acid)-b-poly(ethylene glycol)(PLGA-b-PEG) to form 4Cz IPNDAE nanoparticles(NPs) through flash nanoprecipitation(FNP). By using the FNP method, the NPs were prepared within milliseconds in a confined impingement jets dilution(CIJ-D) mixer. Quenching and recovery of fluorescence could achieve in the presence of DAE under 475 nm and 560 nm irradiation.Appropriate structure and fluorescent properties of the nanoparticles can be tuned by external conditions for their efficient fluorescence resonance energy transfer(FRET) in a kinetic stabilization process. This NPs formation process was further optimized by varying the dilution ratio, Reynolds number(Re) and polymer concentration to modulate the mixing and particle nucleation and growth process. The size and fluorescence switching properties of the NPs were systematically investigated in solution and in cellular uptake experiments. This work is anticipated to provide a simple and highly effective engineering strategy for the modulation of fluorescence switching nanoparticles and beneficial to its engineering application.

Enhanced transdermal delivery of meloxicam by nanocrystals: Preparation, in vitro and in vivo evaluation

Meloxicam(MLX) is efficient in relieving pain and inflammatory symptoms, which, however, is limited by the poor solubility and gastrointestinal side effects. The objective of this study is to develop a nanocrystal formulation to enhance transdermal delivery of MLX. MLX nanocrystals were successfully prepared by the nanoprecipitation technique based on acidbase neutralization. With poloxamer 407 and Tween 80(80/20, w/w) as mixed stabilizers,MLX nanocrystals with particle size of 175 nm were obtained. The crystalline structure of MLX nanocrystals was confirmed by both differential scanning calorimetry and X-ray powder diffractometry. However, the nanoprecipitation process reduced the crystallinity of MLX.Nanocrystals increased both in vitro and in vivo transdermal permeation of MLX compared with the solution and suspension counterparts. Due to the enhanced apparent solubility and dissolution as well as the facilitated hair follicular penetration, nanocrystals present a high and prolonged plasma MLX concentration. And 2.58-and 4.4-fold increase in AUC0 →2 4 h was achieved by nanocrystals comparing with solution and suspension, respectively. In conclusion, nanocrystal is advantageous for transdermal delivery of MLX.

Enhancing pharmaceutical potential and oral bioavailability of Allium cepa nanosuspension in male albino rats using response surface methodology

Objective:To enhance the pharmaceutical potential and oral bioavailability of quercetin contents of Allium cepa peel extract by novel nanosuspension technology.Methods:Nanoprecipitation approach was successfully used for the formulation of nanosuspension.To obtain pharmaceutical-grade nanosuspension with minimum particle size and polydispersity index,sodium lauryl sulphate was selected as a stabilizer.Important formulation parameters were statistically optimized by the response surface methodology approach.The optimized nanosuspension was subjected to stability and in vitro dissolution testing and characterized by scanning electron microscopy,atomic force microscopy,Fourier transform infrared spectroscopy,and zeta sizer.To evaluate the preeminence of nanosuspension over coarse suspension,comparative bioavailability studies were carried out in male albino rats.The pharmaceutical potential of developed nanosuspension was evaluated by antioxidant,antimicrobial,and toxicity studies.Results:The optimized nanosuspension showed an average particle size of 275.5 nm with a polydispersity index and zeta potential value of 0.415 and−48.8 mV,respectively.Atomic force microscopy revealed that the average particle size of nanosuspension was below 100 nm.The formulated nanosuspension showed better stability under refrigerated conditions.Nanosuspension showed an improved dissolution rate and a 2.14-fold greater plasma concentration of quercetin than coarse suspension.Moreover,the formulated nanosuspension exhibited enhanced antioxidant and antimicrobial potential and was non-toxic.Conclusions:Optimization of nanosuspension effectively improves the pharmaceutical potential and oral bioavailability of Allium cepa extract.

Development and evaluation of a hot-rolled 780 MPa steel sheet with an ultra-high expansion ratio

This paper explores the development of a 780 MPa hot-rolled high-strength steel with an ultra-high hole expansion ratio(HER) by using a nanoprecipitation-controlled technology.Systematic analysis and evaluation of an industrially produced steel sheet have been performed to investigate the microstructure, nanoprecipitates, tensile properties, HER,bendability, and forming limit diagram.The newly developed 780 MPa hot-rolled high-strength steel sheet is composed of a fully ferritic microstructure of approximately 5 μm with precipitates of approximately 4-5 nm in ferrite grain interiors.The yield strength and tensile strength can reach above 700 and 780 MPa, respectively.Moreover, the fractured elongation is higher than 19% in the transversal direction, and the average HER exceeds 70%.Furthermore, the newly developed 780 MPa high-strength steel has good bendability reaching R/t=0.2 at 90°.Compared with the conventional 780 MPa high-strength steel, the newly developed 780 MPa high-strength steel exhibits superior forming ability, which is suitable for the production of complex components.High-cycle fatigue indicates that the fatigue limit of the newly developed high-strength steel is 430 MPa under a stress ratio of r=-1,indicating good fatigue properties.The excellent combined mechanical properties of the newly developed 780 MPa high-strength steel are attributed to the grain-refined ferritic microstructure with nanoprecipitates in ferrite grain interiors.

Dye Regeneration Kinetics of C343-Sensitized Nickel Oxide Investigated by Scanning Electrochemical Microscopy

Scanning electrochemical microscopy (SECM) feedback mode has been used to investigate kinetics of dye regeneration in DSSC. Organic dye C343 and CW1 are used as sensitizers for nickel oxide (NiO) photoelectrochemical cells. The influence of film thickness on dye regeneration kinetics in the films for NiO/C343 for six different films was investigated. SECM was used to analyze effective rate constant, keff and reduction rate kred, absorption cross section, Φhv for the dye regeneration process. The data reveal a significant variation of keff and kred with a variation of light intensity, sample thickness and dye difference. This research found remarkable dependence of the dye regeneration kinetic parameters on illumination flux, dye types and film thickness of electrode.

Antioxidant and Cytotoxic Activities of Clove Oil Nanoparticles and Evaluation of Its Size and Retention Efficiency

A derivation of the nanoprecipitation technique without the presence of surfactants to reduce the nanoparticle size is herein proposed. The absence of surfactant in the nanoprecipitation technique allows capturing particles with a smaller diameter than nanoparticles containing surfactants, facilitating the migration of antioxidant nanoparticles in film packaging. Biodegradable PLA nanoparticles with clove oil were produced and characterized by dynamic light scattering, zeta potential, Fourier transform infrared spectroscopy, retention efficiency, cytotoxicity, and antioxidant activity. The particle sizes obtained were smaller than those commonly produced by nanoprecipitation, monodispersed and stable for 6 months. The antioxidant activity showed that the encapsulated form of clove oil had greater antioxidant activity than unencapsulated clove oil. The addition of PLA nanoparticles decreased the cytotoxic action of eugenol, the main antioxidant component of clove oil.

Preparation of microparticles and nanoparticles using membrane-assisted dispersion,micromixing,and evaporation processes

Synthetic microporous membranes are increasingly used for energy-efficient and controlled production of micro-and nanoparticles and micro-and nanoemulsions with tuneable morphology and physico-chemical properties through various micromixing,emulsification,and evaporation processes.In emul-sification processes,the membrane pores are used for dispersed phase injection and size-controlled generation of droplets and droplet-templated particles.In micromixing processes,membrane is utilised as a micromixer for mixing two miscible liquids,usually solvent and antisolvent-rich solutions,which leads to the creation of supersaturation and subsequent nanoprecipitation or crystallisation.In mem-brane evaporation processes,membrane is used to prevent phase dispersion while allowing efficient molecular diffusion of solvent and/or antisolvent vapour through gas-filled pores.Membrane dispersion processes can be operated continuously by decoupling shear stress on the membrane surface from cross flow using tube insets,flow pulsations,swirling flow,membrane oscillations or membrane rotations.Droplet generation and solidification can be performed continuously in a single pass by connecting membrane module with a downstream reactor.Membrane dispersion processes can be used for pro-duction of nanoparticles such as nanovesicles(liposomes,micelles,ethosomes,and niosomes),nanogels,polymeric,lipid and metallic nanoparticles,and nanocrystals.The main advantages of membrane-assisted particle generation are in low energy consumption,controlled geometry and hydrodynamic conditions at the microscale level,flexible throughput due to modular and scalable design of membrane devices,and a wide choice of available microporous membranes with various wall porosities,wetta-bilities,pore sizes,and pore morphologies to suit different applications.

Synthesis and application of green solvent dispersed organic semiconducting nanoparticles

Organic photovoltaic semiconductors have made significant progress and have promising application prospects after decades of development.When compared with traditional semiconductors,the solution method for preparing photovoltaic semiconductors shows the advantages of low cost and convenient preparation.However,because of the extremely poor solubility of the polymers used to prepare semiconductors,toxic solvents must be used when using the solution method,which has significant negative effects on the environment and operators and severely limits its development prospects.Organic nanoparticles(NPs),on the other hand,can avoid these issues.Because NPs are typically water or alcohol-based,no toxic solvents are used.Furthermore,NPs have been used in organic solar cells,hydrogen catalysis,organic light-emitting diodes,and other fields after nearly two decades of development,and their preparation methods have been developed.We describe the preparation,optimization,and application of NPs in photovoltaic semiconductors in this review.

Preparation and characterization of octenyl succinic anhydride nano starch from tiger nut meals

Tiger nut(Cyperus esculentus L.)is an ideal raw material for oil extraction,but starch-rich tiger nut meal,a by-product of oil extraction,has not been fully utilized.For this,starch was isolated from tiger nut meal,and then starch nanoparticles were prepared by gelatinization,ultrasonication and nanoprecipitation under different conditions.The preparation parameters were optimized by measuring the particle size with dynamic light scattering,and the physicochemical properties of native starch and nano starch were evaluated.The results showed that,compared to native starch,starch nanoparticle(nano starch)has a higher amylose content(39.05%),solubility(56.13%),and swelling power(58.01%).Furthermore,native starch and nano starch were esterified with octenyl succinic anhydride(OSA),respectively,conferring amphiphilic properties.The effects of OSA modification on the resistant starch content,thermal properties,and microstructure of starches were characterized.The resistant starch content of tiger nut native starch increased by 10.81%after OSA modification,while the resistant starch content of OSA nano starch increased to 37.76%.Compared to native starch,the gelatinization temperature of OSA nano starch decreased by 2.7℃ and nano starch decreased by 5.68℃.OSA modified nano starch showed a unique microstructure,such as a slender fiber structure and a regular oblate structure.The hydrophobic OSA groups aggregated to form hydrophobic cavities with a hydrophilic surface in the aqueous phase.The findings presented in this investigation provide a better understanding of the design and development of OSA nano starch and provide valuable guidance to further enhance the added value of tiger nuts and future applications in the food industry.

Ultrastrong and ductile(CoCrNi)_(94)Ti_(3)Al_(3)medium-entropy alloys via introducing multi-scale heterogeneous structures

The coarsening-grained single-phase face-centered cubic(fcc)medium-entropy alloys(MEAs)normally exhibit insufficient strength for some engineering applications.Here,superior mechanical properties with ultimate tensile strength of 1.6 GPa and fracture strain of 13.1%at ambient temperature have been achieved in a(CoCrNi)_(94)Ti_(3)Al_(3)MEA by carefully architecting the multi-scale heterogeneous structures.Electron microscopy characterization indicates that the superior mechanical properties mainly originated from the favorable heterogeneous fcc matrix(1-40μm)and the coherent sphericalγ’precipitates(10-100 nm),together with a high number density of crystalline defects(2-10 nm),including dislocations,small stacking faults,Lomer-Cottrell locks,and ultrafine deformation twins.