Manipulation Of Particle Size Research Articles

Research Strategies for Precise Manipulation of Micro/Nanoparticle Drug Delivery Systems Using Microfluidic Technology: A Review

AbstractMicrofluidic technology facilitates precise control over fluid mixing and interactions between the components, including self-assembly and precipitation. It offers new options for accurately manufacturing particles and holds significant potential in advancing micro/nanoparticle drug delivery systems (DDSs). Various microchannel/microfluidic chips have been explored to construct micro/nanoparticle DDSs. The precise manipulation of particle size, morphology, structure, stiffness, surface characteristics, and elasticity through microfluidic technology relies on specific microchannel geometrical designs and the application of exogenous energy, adhering to the principles of fluid motion. Consequently, this enables reproducible control over critical quality attributes (CQAs), such as particle size and distribution, encapsulation efficiency, drug loading, in vitro and in vivo drug delivery profiles, Zeta potential, and targeting capabilities, for micro/nanoparticle DDSs. In this review, we categorize microfluidic techniques and explore recent research developments in novel microchannel structures spanning the past 5 years (2018–2023) and their applications in micro/nanoparticle DDSs. Additionally, we elucidate the latest manipulation strategies of microfluidic techniques that impact foundational structures related to the CQAs of micro/nanoparticle DDSs. Furthermore, we offer insights into the industrial applications and challenges microfluidic techniques face in the context of novel micro/nanoparticle DDSs.

(Invited) Thermal Properties of NMC Cathode Materials

NMC (LiNixMnyCozO2; x+y+z»1) materials deliver high capacity and excellent performance when used as cathodes in lithium-ion batteries. Increasing demand for higher energy density and concerns about the cost and ethics of using cobalt have prompted battery manufacturers to use Ni-rich formulations such as LiNi0.6Mn0.2Co0.2O2 (NMC622) and LiNi0.8Mn0.1Co0.1O2 (NMC811). The thermal stability of (partially) delithiated NMCs is known to decrease with increasing Ni content, however, so that scenarios of fires and other safety events become more distinct possibilities. To investigate the thermal properties of Ni-rich NMCs, we prepared partially and fully delithiated Ni-rich NMCs corresponding to various states-of-charge by chemical methods. We then studied the bulk and surface properties of these materials as they were heated or after they were heated, using a variety of ex situ and in situ synchrotron methods to understand the chemical changes that occur. Of particular concern are reactions that result in release of oxygen. Heated materials progress through a series of bulk structural changes from layered to spinel to rock salt as temperatures rise. Transition temperatures depend on both lithium and nickel content, with bulk changes evident at temperatures as low as 150°C. Surface-sensitive techniques such as soft X-ray absorption spectroscopy (sXAS) indicate that subtle changes that lead to oxygen release can happen well below these temperatures. The thermal behavior of the Ni-rich materials is very complex, and involves lattice transformation, transition metal migration and valence change and lithium redistribution. Moreover, these changes are dependent upon primary particle size, with smaller particles reacting at lower temperatures than larger ones. These observations suggest that materials can be engineered (through primary particle size manipulation, for example) to improve thermal robustness, and therefore, safety and reliability of lithium-ion batteries.

The sensory and physical properties of Shortbread biscuits cooked using different sucrose granule size fractions.

A rich sugar diet has negative health implications so it is necessary to reduce sugar where possible. The objective of this study was to determine if different sugar size fractions could increase the sweetness intensity of Shortbread biscuits and therefore, permit sugar reduction. For this, the unground commercial sugar (Control, 102 to 378µm) and two of its sieved separates, (Coarse (C), 228 to 377µm and Fine (F), 124 to 179µm) were investigated in biscuit formulation with the following content: Control 100% or 50%; (C), 100 or 50% and (F), 100 or 50% or its initial content. Biscuits were tested using sensory (hedonic and intensity), physical (dimensions, fracture properties, color), and compositional analyses. Trends showed that samples containing C-sugar with its 50% content were more preferable than samples containing the Control and F- sugar fractions at the same level without impact upon acceptability of the final product in all three sugar fraction sizes. As sweetness intensity scores correlated directly with flavor liking scores, these findings promote the use of this sugar fraction in the formulation of low-sugar baked biscuits. Sugar particle size manipulation could be used as a viable, cheap, technological approach to reduce sugar in baked goods and therefore promote consumer acceptable and commercially available baked biscuits products. PRACTICAL APPLICATION: In order to reduce sucrose content in products one of the approaches might be via the utilization of small sugar particles which has been shown to increase the intensity of sweetness in chocolate brownies, which has been previously shown by Richardson etal. in 2018. This study investigates the use of a clean label approach in sugar reduction of short bread biscuits. This approach involves decreasing the sugar particles size and demonstrates how reducing the content to half of its initial content formulation will affect the sensory perception and physical properties.

Engineering nanoparticles to tackle tumor barriers.

Engineering nanoparticles (NPs) as delivery systems of anticancer therapeutics has attracted tremendous attention in recent decades, and some nanoscale drug formulations have been approved for clinical use. However, their therapeutic efficacies are still limited by the presence of a series of biological barriers during the delivery process. Among these obstacles, tumor barriers are generally recognized as the bottleneck, because they dominate the NP extravasation from the tumor vasculature and penetration into the tumor parenchyma. Therefore, this review first discussed tumor barriers from two aspects: tumor vascular barriers and tumor stromal barriers. Pathological features of the two sets of barriers as well as their influence on the delivery efficacy were described. Then, we outlined strategies for engineering NPs to overcome these challenges: increasing extravasation through physical property optimization and tumor vascular targeting; and facilitating deep penetration through particle size manipulation, modulation of the tumor extracellular matrix, and some new mechanisms. This review will provide a critical perspective on engineering strategies for more efficient nanomedicine in oncology.

Enhancing the prebiotic effect of cellulose biopolymer in the gut by physical structuring via particle size manipulation.

Cellulose is generally recognised as dietary fibre with no limit of permissible quantity in food, and its consumption may modulate digesta content and impact positively on the gastrointestinal physiology and gut microflora. However, cellulose in its native form possessed inherent undesirable physical properties, making it unattractive for food applications. Here, we postulate that by changing cellulose size to nanometric scale, its prebiotic effect would be altered and fermented differently in contrast with micro size cellulose by the gut microbiome and promote the yield of metabolites such as short chain fatty acids (SCFAs). Using faecal matter from three healthy human donors as microbial source, in vitro fermentation of variable size fractions of cellulose from the same were fermented under anaerobic conditions, and SCFAs as well Bifidobacterium selectively isolated and analysed. The increase in production of acetate (194%), butyrate (224%) and propionate (211%) after 24h of fermentation was significantly promoted by the size reduction and revealed size-dependent relationship as exemplified R2 values >0.83. Consequently, gavaging rats with nanometric size cellulose (125nm) significantly (p<0.05) increased these SCFAs yields as well Bifidobacterium counts in contrast with both control and the micro scale size cellulose. Therefore, engineered nanocellulose might have beneficial physiological impact on the gut with improved prebiotic effect.

Particle size manipulation as an influential parameter in the development of mechanical properties in electric arc furnace slag-based AAM

Alkali-activated materials (AAM) have gained recognition as a promising alternative to technical ceramic and building materials owing to the lower energy demands for production and the potential to use slag as a precursor. In the present study, five sets of slag-based AAM pastes were prepared with different particle sizes (fractions d < 63, 63 < d < 90, and 90 < d < 125 μm in different mass ratios) under the same curing regime and using a fixed precursor to activator (water) mass ratio. Precursors and the hardened AAM are evaluated using BET, XRD, XRF, SEM, FTIR, reactivity of precursors by leaching, and mercury intrusion porosimetry (MIP). Chemical analysis indicated only marginal differences among the different-sized fractions of input materials, whereas the BET surface area and reactivity among the precursors differed significantly–smaller particles had the largest surface area, and thus, higher reactivity. The mineralogical differences between the precursors and hardened AAM were negligible. The results revealed that compressive strength was significantly influenced by particle size, i.e., a threefold increase in strength when the particle size was halved. Microstructural evaluation using MIP confirmed that the porosity was the lowest in AAM with the smallest particle size. The low porosity and high reactivity of the fine fractions led to the highest compressive strength, confirming that manipulation of particle size can significantly influence the mechanical properties.

Halide‐Induced Leaching of Pt Nanoparticles – Manipulation of Particle Size by Controlled Ostwald Ripening

AbstractThe synthesis of “surfactant‐free” Pt nanoparticles (NPs) in alkaline ethylene glycol (EG), initially introduced in 2000, is of fundamental interest for the preparation of catalysts. Often a suspension of colloidal Pt NPs prepared by this method is stored and upon demand further processed to obtain supported catalysts such as Pt−C or Pt−Al2O3. In this study it is shown that in such colloidal suspensions in the presence of halides, e. g. from the metal precursor salt, leaching of Pt NPs takes place. Metal leaching poses a significant challenge for catalyst stability. However, if the reaction conditions are chosen appropriately, the here identified leaching process can be utilized to achieve particle growth by Ostwald ripening in a controlled manner. By changing the chemical nature of the metal precursor salt and variation of the reaction time, Pt NPs with a narrow size distribution between 1 to 4 nm are obtained without any need of surfactants. Subsequently, the obtained particles can be transferred into low‐boiling organic solvents, which then allows for coating of deliberately chosen supports to prepare e. g. model catalyst which are tailored in terms of particle size and support material. The suitability of such materials for catalytic investigations is demonstrated by using CO oxidation as a model reaction and it is shown that the catalytic activity (surface normalized) depends on the size of Pt NPs under the applied reaction conditions.

The impact of sugar particle size manipulation on the physical and sensory properties of chocolate brownies

The overall objective of this research was to assess the effect of sugar particle size manipulation on the physical and sensory properties of chocolate brownies. A control sugar (commercially available, 200-5181 μm) and four of its sieved sugar separates (mesh size of 710, 500, 355 and 212 μm) were determined by grinding and sieving. The particle diameter and diameter distributions of the control sugar and each sugar fraction were measured. As a result, five sugar treatments were determined for chocolate brownie formulations; Control (C200-5181 μm), Large-particle replacement (LPR924-1877 μm), Medium-particle replacement (MPR627-1214 μm), Small-particle replacement (SPR459-972 μm) and a known MIX sample. Samples were tested using sensory (hedonic & intensity), instrumental (texture and colour) and compositional analyses (moisture and fat). Brownie samples containing the smallest sugar fraction (SPR459-972 μm) were perceived as significantly sweeter than any other sample (p < 0.05). Brownies containing this fraction were also the softest and moistest samples (p < 0.05). Texture liking was significantly associated with the LPR924-1877 μm brownie (p < 0.05). Darkness of brownie samples increased (p < 0.05) as sugar particle size decreased. Therefore, sugar particle size alteration affects the physical and sensory properties of chocolate brownies and could be used as a viable approach to reduce sugar in confectionery-type products.

Size and morphology manipulation of nickel nanoparticle in inductively coupled thermal plasma synthesis

Nickel nanoparticles for the internal electrode of multi-layer ceramic capacitors have been persistently developed in response to the industrial requirements for volumetric capacitance increases. In this context, the manipulation of particle size and morphology is still critical. In the present study, Ni nanoparticles were synthesized by feeding Ni(OH)2 micro-powder feedstock into argon-hydrogen thermal plasma. The injected micro-powder feedstock was fully vaporized and reduced, owing to the high energy density and reactivity of thermal plasma. In association with particle size and morphology, the mass feed-rate and quenching gas were chosen as the variables affecting condensation behaviors from the viewpoint of characteristic times in a general collision-coalescence model. Particle size and morphology varied significantly from well-dispersed coarse nanoparticles to aggregates of fine primary nanoparticles, according to the process parameters. The process parameters' effects on the synthesized nanoparticle properties were considered. In addition, spherical nanoparticles with internal band-like sub-structures were frequent, particularly for coarse particles. From the transmission electron microscopy study and molecular dynamic simulation, it was proven that the band-like sub-structure is nano-twin, and the twin boundary is stabilized by the spontaneous rotating of colliding particles.

Self-emulsifying lipid formulation: an overview.

An important step in oral drug development is to identify drug candidates that show sufficient aqueous solubility and could resist or bypass first-pass metabolism in order to overcome bioavailability problems. Aqueous solubility is characteristically low for Biopharmaceutical Classification System (BCS) class II and class IV drug candidates. Several formulation approaches are being identified to overcome the low solubility aspect of a drug candidate such as particle size manipulation, solid dispersions, inclusion complexes and several of nanoparticle-based options. However, the formulation for drug candidates that in addition to low aqueous solubility shows high intestinal and first-pass metabolism is challenging. The self-emulsifying lipid formulations (SELF) provide a mean for sidestepping these factors and improve the bioavailability of lipophilic and highly first- pass metabolised drugs. Nevertheless, formulation of a successful SELF requires an exhaustive understanding of the component used to formulate them, the behaviour of the formulation within the gastrointestinal (GI) milieu and the mechanism by which the drug is released and absorbed. This review gives a brief description of the formulation aspects of SELF and their potential role to mitigate the bioavailability problem related to lipophilic and highly first- pass metabolised drugs.

Direct manipulation of particle size and morphology of ordered mesoporous silica by flow synthesis

Flow-synthesis of mesoporous silica allows deliberate and precise control over the size and shapes and enables the preparation of complex microstructures (i.e., hollow spheres).

Manipulation of Particle Size and Sorption Capability of Nano-Scale Magnetite via Controlling Surface Coating

Non-point source nutrient release from land to water, which leads to the eutrophication and toxic algal blooms in natural water, is not easy to control effectively because in-situ injection of suspended particles is often failed to reach deep soils due to nanoparticles tending to agglomerate into micro particles. In this work, we found that particle sizes of synthetic magnetite nanoparticles (Fe3O4) and sorption capacity of phosphate were controllable by manipulating the surface coverage of stabilizer (starch). The sorption density and starch stabilized particle sizes were positive correlation. In order to enhance the stability and dispersibility of the nanoparticles, the particle sizes were reduced to nano-scale with high dosage of starch, which weakened the phosphate sorption capability. To recover the activity of the nanoparticles, alpha-amylase was employed to degrade the surface coating. The phosphate sorption capacity was almost doubled when alpha-amylase was applied comparing with that without alpha-amylase. Column testes indicated that highly stabilized nanoparticles could be delivered to the targeted depth of soil column, and the sorption activity was recovered by the in-situ biodegradation of starch. The technology provides methods for in situ immobilization of phosphorus in over fertilized soils, which is significant in controlling the eutrophication of aquatic environments.

The potent antimicrobial properties of cell penetrating peptide-conjugated silver nanoparticles with excellent selectivity for Gram-positive bacteria over erythrocytes

Silver nanoparticles are of great interest for use as antimicrobial agents. Studies aimed at producing potent nano-silver biocides have focused on manipulation of particle size, shape, composition and surface charge. Here, we report the cell penetrating peptide catalyzed formation of antimicrobial silver nanoparticles in N,N-dimethylformamide. The novel nano-composite demonstrated a distinctly enhanced biocidal effect toward bacteria (gram-positive Bacillus subtilis, gram-negative Escherichia coli) and pathogenic yeast (Candida albicans), as compared to triangular and extremely small silver nanoparticles. In addition, a satisfactory biocompatibility was verified by a haemolysis test. Our results provide a paradigm in developing strategies that can maximize the silver nanoparticle application potentials while minimizing the toxic effects.

Synthesis of Gadolinium Nanoscale Metal−Organic Framework with Hydrotropes: Manipulation of Particle Size and Magnetic Resonance Imaging Capability

Gadolinium metal-organic framework (Gd MOF) nanoparticles are an interesting and novel class of nanomaterials that are being studied as a potential replacement for small molecule positive contrast agents in magnetic resonance imaging (MRI). Despite the tremendous interest in these nanoscale imaging constructs, there are limitations, particularly with respect to controlling the particle size, which need to be overcome before these nanoparticles can be integrated into in vivo applications. In an effort to control the size, shape, and size distribution of Gd MOF nanoparticles, hydrotropes were incorporated into the reverse microemulsion synthesis used to produce these nanoparticles. A study of how hydrotropes influenced the mechanism of formation of reverse micelles offered a great deal of information with respect to the physical properties of the Gd MOF nanoparticles formed. Specifically, this study incorporated the hydrotropes, sodium salicylate (NaSal), 5-methyl salicylic acid, and salicylic acid into the reverse microemulsion. Results demonstrated that addition of each of the hydrotropes into the synthesis of Gd MOFs provided a simple route to control the nanoparticle size as a function of hydrotrope concentration. Specifically, Gd MOF nanoparticles synthesized with NaSal showed the best reduction in size distributions in both length and width with percent relative standard deviations being nearly 50% less than nanoparticles produced via the standard route from the literature. Finally, the effect of the size of the Gd MOF nanoparticles with respect to their MRI relaxation properties was evaluated. Initial results indicated a positive correlation between the surface areas of the Gd MOF nanoparticles with the longitudinal relaxivity in MRI. In particular, Gd MOF nanoparticles with an average size of 82 nm with the addition of NaSal, yielded a longitudinal relaxivity value of 83.9 mM⁻¹ [Gd³⁺] sec⁻¹, one of the highest reported values compared to other Gd-based nanoparticles in the literature to date.

The robustness and flexibility of an emulsion solvent evaporation method to prepare pH-responsive microparticles

A microparticle preparation method based on an emulsion of ethanol in liquid paraffin stabilised using sorbitan sesquioleate which produces enteric microparticles of excellent morphology, size and pH-sensitive drug release was assessed for its robustness to changes in formulation and processing parameters. Prednisolone and methacrylic acid and methyl methacrylate copolymer (Eudragit S) were the drug and polymer of choice. Emulsion solvent evaporation procedures are notoriously sensitive to changes in methodology and so emulsion stirring speed, drug loading, polymer concentration and surfactant (emulsifier) concentration were varied; microparticle size, encapsulation efficiency, yield and in vitro dissolution behaviour were assessed. The yield and encapsulation efficiency remained high under all stirring speeds, drug loadings and polymer concentrations. This suggests that the process is flexible and efficiency can be maintained. Surfactant concentration was an important parameter; above an optimum concentration resulted in poorly formed particles. All processing parameters affected particle size but this did not alter the acid resistance of the microparticles. At high pH values the smaller microparticles had the most rapid drug release. In conclusion, the microparticle preparation method was resistant to many changes in processing, although surfactant concentration was critical. Manipulation of particle size can be used to modify the drug release profiles without adversely affecting the gastro-resistant properties of these pH-responsive microparticles.

Tobacco industry research and efforts to manipulate smoke particle size: Implications for product regulation

Over the past half-century of cigarette design, tobacco manufacturers have prioritized efficiency of delivery alongside ease of inhalation and use. As a result, the modern cigarette is uniquely effective at facilitating the absorption of nicotine as well as carcinogens and other toxins. The present study draws on internal tobacco company documents to assess industry consideration of the role of smoke particle size as a potentially controllable influence over inhalation patterns and lung exposure. Tobacco manufacturers evaluated particle size manipulation both as a means of controlling physical and sensory product attributes and as a possible approach to reducing health hazards related to exposure. Industry scientists concluded that the smoke aerosol particle distribution of conventional cigarettes, constructed within common parameters, falls within a narrow and effective inhalation range. However, the internal findings suggest that differences in smoke particle size distribution are possible through less conventional approaches to product design. We propose that particle size be included among the many design features to be considered in emerging tobacco product regulation. However, the present review does not address whether particle size regulation would be a plausible means of substantially reducing addictiveness or harmfulness of cigarettes, and therefore we do not propose it as a high-priority target for regulation.