Enhancing Antimicrobial Performance of Gauze via Modification by Ag-Loaded Polydopamine Submicron Particles.

Silver nanoparticles (AgNPs) are known for their antibacterial properties and their ability to promote wound healing. By incorporating silver nanoparticles into medical gauze, the resulting composite material shows promise as an advanced wound dressing. However, clinical applications are hindered by challenges related to the stability of silver nanoparticle loading on the gauze as nanoparticle leaching can compromise antibacterial efficacy. In this study, silver nanoparticles were immobilized onto polydopamine (PDA) submicron particles, which were then used to modify medical gauze. Energy dispersive spectroscopy (EDS) was employed to analyze the elemental distribution on the modified gauze, confirming successful surface modification. The antibacterial properties of the modified gauze were assessed using a laser scanning confocal microscope (CLSM). The results demonstrated a significant reduction in the adhesion rates of Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) by 99.1% and 63%, respectively, on the PDA-Ag-modified gauze. Optical density (OD) measurements at 590 nm indicated that the modified gauze effectively inhibited biofilm formation, underscoring its potent antimicrobial capabilities. Further antibacterial efficacy was evaluated by diluting and plating co-cultured bacterial solutions with the modified dressing, followed by 24 h incubation and colony counting. The gauze exhibited an antibacterial efficiency of 99.99% against E. coli and 99.8% against S. aureus. Additionally, cell compatibility tests, involving the co-culture of PDA-Ag composites with human cells, demonstrated excellent biocompatibility. These findings suggest that PDA-Ag-modified medical gauze holds significant potential for the treatment of infected wounds, offering a promising solution to improve wound care through enhanced antimicrobial activity and biocompatibility.

Investigation on submicron particle separation and deflection using tilted-angle standing surface acoustic wave microfluidics.

With the development of in vitro diagnostics, extracting submicron scale particles from mixed body fluids samples is crucial. In recent years, microfluidic separation has attracted much attention due to its high efficiency, label-free, and inexpensive nature. Among the microfluidic-based separation, the separation based on ultrasonic standing waves has gradually become a powerful tool. A microfluid environment containing a tilted-angle ultrasonic standing surface acoustic wave (taSSAW) field has been widely adapted and designed to separate submicron particles for biochemical applications. This paper investigated submicron particle defection in microfluidics using taSSAWs analytically. Particles with 0.1-1 µm diameters were analyzed under acoustic pressure, flow rate, tilted angle, and SSAW frequency. According to different acoustic radiation forces acting on the particles, the motion of large-diameter particles was more likely to deflect to the direction of the nodal lines. Decreasing the input flow rate or increasing acoustic pressure and acoustic wave frequency can improve particle deflection. The tilted angle can be optimized by analyzing the simulation results. Based on the simulation analysis, we experimentally showed the separation of polystyrene microspheres (100 nm) from the mixed particles and exosomes (30-150 nm) from human plasma. This research results can provide a certain reference for the practical design of bioparticle separation utilizing acoustofluidic devices.

Curcumin-loaded albumin submicron particles with potential as a cancer therapy: an in vitro study.

Curcumin (CUR), a polyphenolic compound, shows promising biological properties, particularly antioxidant activity. However, its medical applications are limited due to its low water solubility, bioavailability, and pH-instability. CUR-loaded albumin microparticles (CUR-HSA-MPs) of submicron size in the range of 800 to 900 nm and a zeta potential of -15 mV were prepared. The CUR loading efficiency was up to 65%. A maximum release of 37% of the encapsulated CUR was observed within 6 h when the CUR-HSA-MPs were dispersed in 50% ethanol in PBS at pH 7, while in RPMI 1640 medium the release was 7%. This demonstrates a sustainable release. The in vitro cytotoxicity of CUR-HSA-MPs showed promising anticancer potential against human hepatocellular carcinoma (Huh-7) and human breast adenocarcinoma (MCF-7) cell lines, although this effect was less pronounced in human dermal fibroblasts (HDFB) and human cholangiocyte (MMN) cell lines. Confocal microscopy was used to confirm the uptake of CUR-HSA-MPs by cancer cells. Our studies revealed that HSA-MPs are potentially promising vehicles for increasing the solubility and bioavailability of CUR.

Size-dependent distribution of metal(loid)s in recent marine sediments of the Adriatic sea.

This paper investigates occurrence of metal(loid)s, and size-dependent changes in their concentration in recent marine sediments from coastal and open-sea environments in the eastern Adriatic. Size fractionation of sediments was performed after removal of organic matter (OM), and the individual fractions, comprising particles below 8 µm, 4 µm, 2 µm, 1 µm and 0.45 µm, were analysed using HR ICP-MS. The concentrations of most elements increased with decreasing particle size, as a result of accumulation of clay minerals and Fe and Mn (oxyhydr)oxides. A decrease in concentrations was observed for Ba, Sr, Ti and U, due to lowering of the carbonate content and presence in the coarse-grained and heavy mineral fraction. The highest element concentrations were determined in the fraction comprising particles below 1 µm. Occasionally, depending on the sedimentological environment and/or the element in question, the peak concentrations occurred in the <2 µm or <0.45 µm fraction. The lowest size-dependent enrichment was observed for elements associated with aluminosilicates (Al, Be, Cs, Co, Fe, K, Li, Rb). A different size-dependent behaviour of the elements was observed between deep-sea areas and shallow environments under greater coastal influence, mainly due to differences in sediment sorting, and between the northern and central vs. southern Adriatic due to the different catchment geologies. The Fe and Mn (oxyhydr)oxides, abundant in the deep-sea sediments, played an important role in the geochemical cycle of As, Cd, Co, Mo, Sb and V.

Characterization and Quantification of Natural and Anthropogenic Titanium-Containing Particles Using Single-Particle ICP-TOFMS.

Titanium-containing nanoparticles (NPs) and submicrometer particles (µPs) in the environment can come from natural or anthropogenic sources. In this study, we investigate the use of single-particle inductively coupled plasma time-of-flight mass spectrometry (spICP-TOFMS) to measure and classify individual Ti-containing particles as either engineered (Ti-eng) or naturally occurring (Ti-nat) based on elemental composition and multielement mass ratios. We analyze mixtures of four Ti-containing particle types: anthropogenic food-grade TiO2 particles and particles from rutile, ilmenite, and biotite mineral samples. Through characterization of neat particle suspensions, we develop a decision-tree-based classification scheme to distinguish Ti-eng from Ti-nat particles and to classify individual Ti-nat particles by mineral type. Engineered TiO2 and rutile particles have the same major-element composition. To distinguish Ti-eng particles from rutile, we developed particle-type detection limits based on the average crustal abundance ratio of titanium to niobium. For our measurements, the average Ti mass needed to classify Ti-eng particles is 9.3 fg, which corresponds to a diameter of 211 nm for TiO2. From neat suspensions, we demonstrate classification rates of 55%, 32%, 75%, and 72% for Ti-eng, rutile, ilmenite, and biotite particles, respectively. Our classification approach minimizes false-positive classifications, with rates below 5% for all particle types. Individual Ti-eng particles can be accurately classified at the submicron size range, while the Ti-nat particles are classified in the nanoregime (diameter < 100 nm). Efficacy of our classification approach is demonstrated through the analysis of controlled mixtures of Ti-eng and Ti-nat and the analysis of natural streamwater spiked with Ti-eng particles. In control mixtures, Ti-eng particles can be measured and classified at particle-number concentrations (PNCs) 60-times lower than that of Ti-nat particles and across a PNC range of at least 3 orders of magnitude. In the streamwater sample, Ti-eng particles are classified at environmentally relevant PNCs that are 44-times lower than the background Ti-nat PNC and 2850-times lower than the total PNC.

Novel zone elution mode in coiled tube field-flow fractionation for online separation and characterization of environmental submicron particles.

Coiled tube field-flow fractionation (CTFFF) is currently applied to environmental and material studies. In the present work, a novel zone elution mode in CTFFF has been proposed and developed. Zone elution mode is based on the separation of particles by stepwise decreasing the flow rate of the carrier fluid and their subsequent elution at a constant flow rate. The fractionation parameters were optimized using a mixture of standard silica submicron particles (150, 390, and 900 nm). Taking samples of volcanic ash as examples, it has been demonstrated that zone elution mode can be successfully used for the fractionation of environmental nano- and submicron particles. For the first time, CTFFF was coupled online with a dynamic light scattering detector for the size characterization of eluted particles. Zone elution in CTFFF can serve for the further development of hyphenated techniques enabling efficient fractionation and size/elemental characterization of environmental particles in nano- and submicrometric size ranges.

Detecting pH of Sub-Micrometer Aerosol Particles Using Fluorescent Probes.

Acidity is one of the most fundamental properties of atmospheric aerosol particles, influencing both chemical processes and environmental impacts. A couple of methods for measuring the pH of aerosol particles have been developed, yet no approach is currently available for quantifying the pH of suspending submicron particles. We developed an aerosol fluorescence cell (AFC) for quantifying the pH of aerosol particles in a continuous flow. Particles containing fluorescent pH probes (fluorescein and Oregon green 488) were injected into the AFC. Ratiometric analysis of pH for these particles was conducted by alternatively exciting them with two wavelengths of diode lasers (450 and 488 nm). The employment of the two types of fluorescent probes allowed the measurement of pH in the range of 2-7. The pH measurement by the AFC for submicron particles was compared with that measured by using pH indicator papers, providing a reasonably good agreement. Measurement of size-selected particles suggested that the AFC approach is applicable to particles of 80 nm in diameter. In combination with recent developments for analyzing renebulized water-soluble matter samples, we suggest that the AFC method can be applied not only for laboratory standards but also for atmospherically relevant samples in the future.

Impact of Stress on the Immunogenic Potential of Adalimumab.

Monoclonal antibodies against tumor necrosis factor-alpha (TNFα) are widely used for treatment of inflammatory diseases. However, despite the inhibitory effect this class of drugs has on the immune system, anti-drug antibodies are often formed with continuous use. Particles formed during stress conditions, which can be used to simulate storage and handling conditions of commercial antibodies, have previously been associated with the formation of anti-drug antibodies. This study investigates the relationship between particles, oligomerization, folding and chemical degradation on the in vitro cytokine response toward the TNFα inhibitor adalimumab. Adalimumab aggregates generated using stir and heat stress were fractionated into distinct sub-populations, and their structure and immunogenic potential were evaluated. A chemically degraded sample of adalimumab was included to compare particle composition with the milder accelerated heat and stir stressed conditions. Particles from stressed adalimumab samples induced elevated cytokine levels and CD4+ T cell proliferation in vitro compared to non-stressed samples. Samples enriched with both submicron and subvisible particles of adalimumab induced the strongest cytokine release and the strongest CD4+ T cell proliferation despite maintaining some TNFα inhibitory functionality. Samples that were stressed and subsequently purified of subvisible and submicron particles did not elicit a significantly higher cytokine response or show increased CD4+ T cell proliferation compared to a non-stressed sample. Oxidation-induced chemical modifications in adalimumab, mainly in Met, His, Trp, and Tyr, were not found to be sufficient in absence of particle formation to induce increased CD4+ T cell proliferation or cytokine release despite less decreased TNFα inhibitory activity of adalimumab. These observations provide further evidence that particles do indeed potentiate the immunogenic potential of adalimumab.

Continuously released Zn2+ in 3D-printed PLGA/ß-TCP/Zn scaffolds for bone defect repair by improving osteoinductive and anti-inflammatory properties.

Long-term nonunion of bone defects has always been a major problem in orthopedic treatment. Artificial bone graft materials such as Poly (lactic-co-glycolic acid)/ß-tricalcium phosphate (PLGA/ß-TCP) scaffolds are expected to solve this problem due to their suitable degradation rate and good osteoconductivity. However, insufficient mechanical properties, lack of osteoinductivity and infections after implanted limit its large-scale clinical application. Hence, we proposed a novel bone repair bioscaffold by adding zinc submicron particles to PLGA/ß-TCP using low temperature rapid prototyping 3D printing technology. We first screened the scaffolds with 1 wt% Zn that had good biocompatibility and could stably release a safe dose of zinc ions within 16 weeks to ensure long-term non-toxicity. As designed, the scaffold had a multi-level porous structure of biomimetic cancellous bone, and the Young's modulus (63.41 ± 1.89 MPa) and compressive strength (2.887 ± 0.025 MPa) of the scaffold were close to those of cancellous bone. In addition, after a series of in vitro and in vivo experiments, the scaffolds proved to have no adverse effects on the viability of BMSCs and promoted their adhesion and osteogenic differentiation, as well as exhibiting higher osteogenic and anti-inflammatory properties than PLGA/ß-TCP scaffold without zinc particles. We also found that this osteogenic and anti-inflammatory effect might be related to Wnt/ß-catenin, P38 MAPK and NFkB pathways. This study lay a foundation for the follow-up study of bone regeneration mechanism of Zn-containing biomaterials. We envision that this scaffold may become a new strategy for clinical treatment of bone defects.

Coagulation effect of atmospheric submicron particles on plant leaves: Key functional characteristics and a comparison with dry deposition.

Submicron particles have become a new focus in research on air pollution control. The abilities of urban tree species to retain particles can be used to alleviate urban haze pollution. However, research has focused mostly on plants and environmental conditions rather than on particle itself. Particle migration and transformation at the leaf-air interface are the key to dust retention. Submicron particles coagulate when they are retained by leaves. In this study, NaCl was used to simulate submicron particles. The average sizes of the particles on the leaves of 10 greening tree species in Shanghai in different seasons were measured using the sweep-resuspension method to characterize the coagulation effect. Thereafter, the effects of leaf characteristics were investigated and analyzed in relation to dry deposition velocity. The results indicated that the particles on the leaves of Ginkgo biloba, Osmanthus fragrans, Sabina chinensis (L.) Ant. "Kaizuca," Cinnamomum camphora, and Metasequoia glyptostroboides were large. The seasonal variability of the sizes of the particles on the leaves of different tree species varied. The average particle size was positively correlated with wax content and negatively correlated with single leaf area; however, the other factors correlated with particle size varied by season. For example, in April, the average particle size was positively correlated with tensile strength, wind resistance, adaxial epidermal roughness, and water potential, whereas the effects of stomatal conductance were more complex. Non-significant correlation was identified between coagulation and dry deposition although both were positively correlated with roughness and wax content. This study explored the effects of leaf characteristics on coagulation. The results may serve as a theoretical foundation for explaining the microscopic process underlying dust retention in plants and may provide a clearer scientific basis for the prevention and control of submicron particle pollution and the selection of urban greening tree species.

Tumor Cell Capture Using Platelet-Based and Platelet-Mimicking Modified Human Serum Albumin Submicron Particles.

The co-localization of platelets and tumor cells in hematogenous metastases has long been recognized. Interactions between platelets and circulating tumor cells (CTCs) contribute to tumor cell survival and migration via the vasculature into other tissues. Taking advantage of the interactions between platelets and tumor cells, two schemes, direct and indirect, were proposed to target the modified human serum albumin submicron particles (HSA-MPs) towards tumor cells. HSA-MPs were constructed by the Co-precipitation-Crosslinking-Dissolution (CCD) method. The anti-CD41 antibody or CD62P protein was linked to the HSA-MPs separately via 1-ethyl-3-(-3-dimethyl aminopropyl) carbodiimide hydrochloride (EDC) and N-hydroxysuccinimide (NHS) EDC/NHS chemistry. The size of modified HSA-MPs was measured at approximately 1 µm, and the zeta potential was around -24 mV. Anti-CD41-HSA-MPs adhered to platelets as shown by flowcytometry and confocal laser scanning microscopy. In vitro, we confirmed the adhesion of platelets to tumor lung carcinoma cells A549 under shearing conditions. Higher cellular uptake of anti-CD41-HSA-MPs in A549 cells was found in the presence of activated platelets, suggesting that activated platelets can mediate the uptake of these particles. RNA-seq data in the Cancer Cell Lineage Encyclopedia (CCLE) and The Cancer Genome Atlas (TCGA) database showed the expression of CD62P ligands in different types of cancers. Compared to the non-targeted system, CD62P-HSA-MPs were found to have higher cellular uptake in A549 cells. Our results suggest that the platelet-based and platelet-mimicking modified HSA-MPs could be promising options for tracking metastatic cancer.

Theophylline-Loaded Pectin/Chitosan Hydrochloride Submicron Particles Prepared by Spray Drying with a Continuous Feeding Ultrasonic Atomizer.

Pectin/chitosan hydrochloride (CHC) particles containing theophylline were prepared by a spray-drying apparatus coupled with a continuous feeding ultrasonic atomizer and a heating column. The formation of the submicron particles was investigated at various compositions of pectin solutions added with a chitosan hydrochloride or calcium chloride solution as a crosslinking agent. Scanning electron microscopic (SEM) images showed the pectin/chitosan hydrochloride particles had spherical and smooth surfaces. Depending on the feeding concentrations, the produced particles had diameters in the range of 300 to 800 nm with a narrow size distribution. Furthermore, the theophylline (TH)-loaded pectin/CHC particles were also prepared by the same apparatus. The TH release from the submicron particles in phosphate-buffered saline at 37 °C was monitored in real-time by a UV-Visible spectrophotometer. The Ritger-Peppas model could well describe the TH release profiles. All the diffusional exponents (n) of the release systems were greater than 0.7; thus, the transport mechanism was not a simple Fickian diffusion. Particularly, the n value was 1.14 for the TH-loaded particles at a pectin/CHC weight ratio of 5/2, which was very close to the zero-order drug delivery (n = 1). Therefore, the constant drug-release rate could be achieved by using the spray-dried pectin/CHC particles as the drug carrier.

Semiconducting Soft Submicron Particles from the Microwave-Driven Polymerization of Diaminomaleonitrile.

The polymers based on diaminomaleonitrile (DAMN polymers) are a special group within an extensive set of complex substances, namely HCN polymers (DAMN is the formal tetramer of the HCN), which currently present a growing interest in materials science. Recently, the thermal polymerizability of DAMN has been reported, both in an aqueous medium and in bulk, offering the potential for the development of capacitors and biosensors, respectively. In the present work, the polymerization of this plausible prebiotic molecule has been hydrothermally explored using microwave radiation (MWR) via the heating of aqueous DAMN suspensions at 170-190 °C. In this way, polymeric submicron particles derived from DAMN were obtained for the first time. The structural, thermal decomposition, and electrochemical properties were also deeply evaluated. The redox behavior was characterized from DMSO solutions of these highly conjugated macromolecular systems and their potential as semiconductors was described. As a result, new semiconducting polymeric submicron particles were synthetized using a very fast, easy, highly robust, and green-solvent process. These results show a new example of the great potential of the polymerization assisted by MWR associated with the HCN-derived polymers, which has a dual interest both in chemical evolution and as functional materials.

Removal of Size-Dependent Submicron Particles Using Metal-Organic Framework-Based Nanofiber Air Filters.

Particulate matter poses a serious threat to human health. In particular, exposure to submicron particles can result in more severe health effects as they can deposit more deeply into human tissues. Metal-organic framework (MOF)-based nanofiber filters are regarded as promising candidates for efficient particle control. In this study, ZIF-8@PAN nanofiber filters that were developed via an in situ growth strategy were selected for the filtration of submicron particles. The addition of ZIF-8 more effectively enhanced the filtration of particles with smaller sizes. For the most penetrating particle size of around 0.3 µm, the MOF-based nanofiber filter exhibited an 8.9% increase in filtration efficiency compared with that of the pure nanofiber filter. Meanwhile, for particles with large aerodynamic diameters (in the range of 0.7-1 µm, for example), the role of ZIF-8 was negligible. This work provides important insights into the filtration performance of MOF-based nanofiber filters in capturing submicron particles and may aid in designing nanofiber filters for efficient control of particles.

Carrier-Free Small Molecular Self-Assembly Based on Berberine and Curcumin Incorporated in Submicron Particles for Improving Antimicrobial Activity.

Nanocarrier-based pesticide formulations have been severely restricted in agriculture practices due to their high-cost preparation process, poor loading capacity, and toxicity issues. To overcome these issues, carrier-free small molecular self-assembled submicron particles (SMPs) with an improved photoactivated antimicrobial activity based on two natural microbicides berberine hydrochloride (BBR) and curcumin (CM) are constructed by noncovalent interactions through a simple and fast preparation process (solvent exchange method) without using any adjuvant. The results show that the optimized molar ratio of BBR to CM is 2:1 at pH 5 and 25 °C in an aqueous solution for the formation of B-C SMPs. The obtained B-C SMPs exhibit excellent physicochemical properties, such as uniform morphology (407 nm), low polydispersity index (0.283), and strong ζ-potential (+24.4 mV). The antibacterial activities of B-C SMPs against Pseudomonas syringae pv. lachrymans, Clavibater michiganensis subsp. Michiganensis, and Sclerotinia sclerotiorum are 4, 2, and 1.5 times that of B + C MIX, respectively, suggesting a synergistic antimicrobial activity based on BBR and CM incorporation in the submicron particles. The genotoxicity evaluation results show that the self-assembled B-C SMPs are harmless to plant cells. Therefore, due to rational utilization of natural resources (natural microbicides, sunlight, and oxygen), carrier-free small molecular self-assembled B-C SMPs with synergistic photoactivated antimicrobial activity developed by a simple and fast preparation process would have great potential for sustainable plant disease management.

Characterization of submicron aerosol particles in winter at Albany, New York.

A thorough understanding of chemical composition, particle pH, and pollutant emissions is essential to address the climate and human health effects of atmospheric particles. In this study, we used a High-Resolution Time-of-Flight Aerosol Mass Spectrometer (HR-ToF-AMS) and Scanning Mobility Particle Sizer (SMPS) to characterize the composition of submicron particles. Moreover, we applied the ISORROPIA-II model to analyze the particle acidity effect on the compositional characterization of submicron particles from December 22, 2016 to January 7, 2017 in Albany, New York, USA. The results indicated that aerosols with mobility diameter from SMPS in the range 200-400 nm were the main contributors to the mass during the measurement period. The dominance of organics (47%) and sulfate (16%) was similar to previous observations in the eastern United States in Winter 2015, while the fraction of nitrate (23%) was much higher. Moreover, nitrate could easily form at colder temperatures and lower RH levels even when there were more acidic particle periods during the measurement period in Albany. The ISORROPIA-II model indicated that there were more acidic particles, which was estimated using pH values. Lower temperature conditions tended to favor nitrate formation. The nitrate concentration exceeded that of sulfate in the measurement period, even though the SO2 and NOx emissions were similar. The organics in submicron particles were strongly influenced by the local emissions in winter. However, the inorganic compounds in submicron particles could be derived from regional transport as their pollution sources originated from different directions. This may help strategize emission reductions in the future.

Source apportionment of marine atmospheric aerosols in northern South China Sea during summertime 2018.

Marine atmospheric aerosols play important roles in the global radiation balance and climate change. Hence, measuring physiochemical aerosol properties is essential to better understand their formation, aging processes, and source origins. However, high temporal resolution measurements of submicron particles are currently scarce in the northern South China Sea (SCS). In this study, we conducted a ship-based cruise campaign with a scanning mobility particle sizer and an online time of flight aerosol chemical speciation monitor to measure the particle number size distribution (PNSD) and the chemical composition of submicron particles over the northern SCS during summer 2018. The mean concentration of non-refractory submicron particulate matter (NR-PM1) was generally 9.11 ± 4.86 µg m-3; sulfate was the most abundant component, followed by organics, ammonium, nitrate, and chloride. Positive matrix factorization (PMF) analysis was applied to the PNSD (size PMF) and organic aerosols (OA PMF) and further investigated the source apportionment of the submicron particles. The size PMF identified four factors, including ship exhaust, ship influencing marine primary, continent affected marine secondary, and mixed accumulation aerosols. The most abundant particles in the number concentration were associated with ship emissions, which accounted for approximately 44 %. The submicron organic aerosols were highly oxidized and composed of low-volatility oxygenated OA (LV-OOA, 68 %), semi-volatile OOA (SV-OOA, 21 %), and hydrocarbon-like OA (HOA, 11 %). The backward trajectory of air masses showed that the northern SCS was most frequently (64.7 %) influenced by air masses from the Indo-Chinese Peninsula (ICP) during the campaign, implying that pollutants from ICP have a significant impact on the atmosphere of the northern SCS during summer. Thus, in situ ship-based cruise measurements can provide valuable data on the physiochemical characteristics of marine atmospheric aerosols to better understand their source origins.

Daily submicron particle doses received by populations living in different low- and middle-income countries.

In the present study, the daily dose in terms of particle surface area received by citizens living in different low- and middle-income countries, characterized by different lifestyles, habits, and climates, was evaluated. The level of exposure to submicron particles and the dose received by the populations of Accra (Ghana), Cairo (Egypt), Florianopolis (Brazil), and Nur-Sultan (Kazakhstan) were analyzed. A direct exposure assessment approach was adopted to measure the submicron particle concentration levels of volunteers at a personal scale during their daily activities. Non-smoking adult volunteers performing non-industrial jobs were considered. Exposure data were combined with time-activity pattern data (characteristic of each population) and the inhalation rates to estimate the daily dose in terms of particle surface area. The received dose of the populations under investigation varied from 450 mm2 (Florianopolis, Brazil) to 1300 mm2 (Cairo, Egypt). This work highlights the different contributions of the microenvironments to the daily dose with respect to high-income western populations. It was evident that the contribution of the Cooking & Eating microenvironment to the total exposure (which was previously proven to be one of the main exposure routes for western populations) was only 8%-14% for low- and middle-income populations. In contrast, significant contributions were estimated for Outdoor day and Transport microenvironments (up to 20% for Cairo, Egypt) and the Sleeping & Resting microenvironment (up to 28% for Accra, Ghana), highlighting the effects of different site-specific lifestyles (e.g. time-activity patterns), habits, socioeconomic conditions, climates, and outdoor air quality.

Melt milling as manufacturing method for solid crystalline suspensions.

Production of submicron particles (0.1-1 µm) has been identified by the pharmaceutical industry as a key technology to enhance the bioavailability of poorly water-soluble drugs. However, nanosuspensions derived from commonly applied wet milling suffer from long-term stability issues, making further downstream processing necessary. In previous works, the formulation as a long-term stable solid crystalline suspension (SCS) was introduced, for which the crystalline drug is ground in a (molten) hydrophilic carrier matrix. The model formulation of the antimycotic Griseofulvin and the sugar alcohol Xylitol was reused for comparative purposes. Due to process limitations regarding the degree of comminution, the present work demonstrates the application of fine grinding in the framework of SCS manufacturing. A custom-built mill with annular gap geometry successfully yielded particles in the targeted submicron range. A process optimization study lead to improved energy utilization during grinding, which reduced the necessary grinding time and, thereby, the thermal exposition of the drug. Investigation of solid-state properties of the SCS, via differential scanning calorimetry and x-ray powder diffraction, showed no alteration even for extended grinding times. In dissolution experiments, the melt-milled SCS outperformed its predecessors, although mostly agglomerates were found by SEM imaging in the solidified product. In conclusion, melt milling is a valuable tool to overcome low aqueous solubility.