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1.
Toxicol Lett ; 2024 Mar 20.
Artículo en Inglés | MEDLINE | ID: mdl-38518988

RESUMEN

High concentrations of low-density particles may cause effects in acute inhalation toxicity studies which can be easily underestimated or misinterpreted following strictly the OECD TG 436, i.e., limited parameters as mortality and gross lesions will be evaluated only. Seven particle types (synthetic amorphous silica (SAS) HMDZ-SAS, silica gel, pyrogenic SAS, and precipitated SAS, calcium carbonate, aluminum oxide pyrogenic alumina, organic red pigment) were chosen at the highest technically feasible concentration of approximately 500 mg/m3 for acute inhalation studies with an expanded endpoint setup. Therefore additional parameters and a thorough histopathological evaluation of an extensive set of organs, including the respiratory tract emphasizing the nasal cavities were added. Six Crl:WI rats per study were exposed for four hours from which three animals were sacrificed after 24 hours and three animals after 14 days. HMDZ-SAS caused early death in all animals due to blockage of the nasal passages caused by its hydrophobicity. For all other Si-containing compounds, histology revealed minor inflammatory and reactive lesions in lungs after 24 hours that were still present after 14 days, except in silica gel-treated animals. After 14 days, for pyrogenic SAS, precipitated SAS, and pyrogenic alumina, granulomas formed in the BALT and lung-associated lymph nodes. In contrast, the calcium carbonate induced almost no findings, and the red pigment (also tested for the additional dose of 1000 mg/m3) stuck partially to the nasal mucosa without causing pathological damage and partly entered the lungs without showing any adverse effects. The results of the present study highlight the advantage of improving the rather simple study design of acute inhalation studies by implementing an extended study design.

2.
Toxicol Lett ; 2024 Feb 22.
Artículo en Inglés | MEDLINE | ID: mdl-38401876

RESUMEN

Reproducible aerosol generation in combination with stable aerosol properties are essential prerequisites for compliant performance of acute or repeated inhalation toxicity tests of particulate materials according to OECD TG 403, 436, 412, or 413. A frequent problem of powder aerosol generation is the formation of coarse agglomerates with low shear resistance, which are beyond the tolerable size range but not detected by the prescribed aerodynamic measurement techniques by cascade impactor as the measurement conditions cause a disintegration into smaller fragments. But such agglomerates are observed during the transport to the inhalation chambers. These effects particularly apply to high mass concentrations and low-density powders, i.e., pyrogenic oxides. This study describes the transport influence in the airflow on the change of powder aerosols and on their respirability. A simplified short tube set-up was developed for the aerosol transport pre-tests, which allows the determination of the optimal aerosol formation conditions for the inhalation tests. The particles were measured with low shear using laser diffraction measurement or optical particle counters. The calculation of the aerodynamic particle sizes prescribed in the guidelines requires knowledge of the effective particle density of the porous aerosol particles. A practicable method for determining these is presented and described. In the outlook, first low concentration measurements show that clear agglomeration effects can also occur at particle concentrations around 20 mg/m³.

4.
Toxicol Lett ; 2023 Feb 16.
Artículo en Inglés | MEDLINE | ID: mdl-36806657

RESUMEN

Inhalation toxicity testing of particulate materials is mandated for classification. According to CLP, particulate materials should be tested as marketed and many particulate materials are marketed as non-respirable particles. However, OECD TG 413 requires exposure to particle sizes that are respirable and reach the alveoli. The requirement for exposure of rats to respirable particles is thus in contrast to CLP and requires the application of high shear forces. The exposure to artificially small particles causes a number of issues that hamper the interpretation of the results of the testing. These issues are aerosol altering in the exposure system, assessment of the adversity of the inflammatory lung responses, inclusion of recovery groups, and extrapolation of the results to humans exposed under occupational condition. In addition, effects of many particulate materials after testing according to OECD 413 are not intrinsic properties, but a general reaction of the lung to the deposited material, show very similar NOAECs for chemical diverse materials, and often are completely reversible.

5.
Environ Toxicol Pharmacol ; 98: 104079, 2023 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-36796551

RESUMEN

Building demolition following domestic fires or abrasive processing after thermal recycling can release particles harmful for the environment and human health. To mimic such situations, particles release during dry-cutting of construction materials was investigated. A reinforcement material consisting of carbon rods (CR), carbon concrete composite (C³) and thermally treated C³ (ttC³) were physicochemically and toxicologically analyzed in monocultured lung epithelial cells, and co-cultured lung epithelial cells and fibroblasts at the air-liquid interface. C³ particles reduced their diameter to WHO fibre dimensions during thermal treatment. Caused by physical properties or by polycyclic aromatic hydrocarbons and bisphenol A found in the materials, especially the released particles of CR and ttC³ induced an acute inflammatory response and (secondary) DNA damage. Transcriptome analysis indicated that CR and ttC³ particles carried out their toxicity via different mechanisms. While ttC³ affected pro-fibrotic pathways, CR was mostly involved in DNA damage response and in pro-oncogenic signaling.


Asunto(s)
Contaminantes Atmosféricos , Hidrocarburos Policíclicos Aromáticos , Humanos , Material Particulado/análisis , Contaminantes Atmosféricos/análisis , Tamaño de la Partícula , Pulmón , Células Epiteliales , Hidrocarburos Policíclicos Aromáticos/análisis , Inflamación/metabolismo , Daño del ADN , Materiales de Construcción , Fibroblastos
6.
Front Public Health ; 10: 907202, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35784249

RESUMEN

Low density powders have a bulk density of less than 100 kg/m3 and are produced technically by flame pyrolysis of silicon tetrachloride (pyrogenic powders such as pyrogenic silica) or wet-chemically by sol-gel processes (e.g. silica-gel) or precipitation reactions using sodium silicate solution and a mineral acid. The transport and alteration behavior of aerosols from low density powders was investigated in a device for toxicological inhalation studies. The test conditions corresponded to those for acute toxicology studies according to OECD Guideline 436. The use of cascade impactors, required by guideline, has not proven successful for low density powders as the fragile agglomerate structures are destroyed during the measurement. As an alternative and non-invasive measurement method, laser diffraction spectroscopy has proved very successful in the present investigations. In particular, aerosols from pyrogenic powders of low density showed a distinctive tendency to re-agglomerate, especially at concentrations >500 mg/m3mm3. Investigation results indicate that aerosol particle size must be monitored over the entire acute inhalation test period for acute inhalation studies to be performed reliably.


Asunto(s)
Dióxido de Silicio , Administración por Inhalación , Aerosoles/química , Tamaño de la Partícula , Polvos
7.
Front Public Health ; 10: 907078, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35719607

RESUMEN

The aim of the present study was to understand the mechanism of lethality associated with high dose inhalation of a low-density hydrophobic surface-treated SAS observed in some acute inhalation studies. It was demonstrated that physical obstruction of the upper respiratory tract (nasal cavities) caused the effects observed. Hydrophobic surface-treated SAS was inhaled (flow-past, nose-only) by six Wistar rats (three males and three females) in an acute toxicity study at a concentration of ~500 mg/m3 for an intended 4-hr exposure. Under the conditions of the test set-up, the concentration applied was found to be the highest that can be delivered to the test animal port without significant alteration of the aerosol size distribution over time. None of the test- material-exposed animals survived the planned observation time of 4 h; three animals died between 2 34 h after starting exposure and cessation of exposure at 3 14 h, two died after transfer to their cages and the remaining animal was sacrificed due to its poor condition and welfare considerations. Histology accomplished by energy dispersive X-ray (EDX) analysis demonstrated that test material particles agglomerated and formed a gel-like substrate that ultimately blocked the upper respiratory airways, which proved fatal for the rat as an obligatory nose breather. This observation is in line with the findings reported by Hofmann et al. showing a correlation between lethality and hydrophobicity determined by contact angle measurement. The aerosol characterizations associated with this study are provided in detail by Wessely et al.


Asunto(s)
Exposición por Inhalación , Dióxido de Silicio , Aerosoles , Animales , Asfixia , Femenino , Interacciones Hidrofóbicas e Hidrofílicas , Exposición por Inhalación/efectos adversos , Exposición por Inhalación/análisis , Masculino , Cavidad Nasal/química , Ratas , Ratas Wistar , Dióxido de Silicio/análisis , Dióxido de Silicio/toxicidad
8.
BMC Cancer ; 22(1): 570, 2022 May 21.
Artículo en Inglés | MEDLINE | ID: mdl-35597921

RESUMEN

BACKGROUND/AIM: To develop and validate a nebulizer device for anti-cancer research on pressurized intraperitoneal aerosol supply in a preclinical peritoneal metastases (PM) rat model. MATERIAL AND METHODS: For aerosol generation, an ultrasonic nebulizer (USN) was modified. Aerosol analyses were performed ex-vivo by laser diffraction spectrometry (LDS). Intraperitoneal (IP) 99mtechnetium sodium pertechnetate (99mTc) aerosol distribution and deposition were quantified by in-vivo single photon emission computed tomography (SPECT/CT) and compared to liquid IP instillation of equivalent volume/doses of 99mTc with and without capnoperitoneum. PM was induced by IP injection of HCT116-Luc2 human colon cancer cells in immunosuppressed RNU rats. Tumor growth was monitored by bioluminescence imaging (BLI), 18F-FDG positron emission tomography (PET) and tissues examination at necropsy. RESULTS: The USN was able to establish a stable and reproducible capnoperitoneum at a pressure of 8 to 10 mmHg. LDS showed that the USN provides a polydisperse and monomodal aerosol with a volume-weighted diameter of 2.6 µm. At a CO2 flow rate of 2 L/min with an IP residence time of 3.9 s, the highest drug deposition efficiency was found to be 15 wt.-%. In comparison to liquid instillation, nebulization showed the most homogeneous IP spatial drug deposition. Compared to BLI, 18F-FDG-PET was more sensitive to detect smaller PM nodules measuring only 1-2 mm in diameter. BLI, 18F-FDG PET and necropsy analyses showed relevant PM in all animals. CONCLUSIONS: The USN together with the PM rat model are suitable for robust and species-specific preclinical pharmacological studies regarding intraperitoneal delivery of pressurized aerosolized drugs and cancer research.


Asunto(s)
Neoplasias del Colon , Neoplasias Peritoneales , Aerosoles , Animales , Neoplasias del Colon/diagnóstico por imagen , Neoplasias del Colon/tratamiento farmacológico , Fluorodesoxiglucosa F18 , Humanos , Nebulizadores y Vaporizadores , Neoplasias Peritoneales/diagnóstico por imagen , Neoplasias Peritoneales/secundario , Ratas
9.
Sci Rep ; 11(1): 21843, 2021 11 08.
Artículo en Inglés | MEDLINE | ID: mdl-34750488

RESUMEN

Pressurized Intraperitoneal Aerosol Chemotherapy (PIPAC) is a promising approach with a high optimization potential for the treatment of peritoneal carcinomatosis. To study the efficacy of PIPAC and drugs, first rodent cancer models were developed. But inefficient drug aerosol supply and knowledge gaps concerning spatial drug distribution can limit the results based on such models. To study drug aerosol supply/deposition, computed tomography scans of a rat capnoperitoneum were used to deduce a virtual and a physical phantom of the rat capnoperitoneum (RCP). RCP qualification was performed for a specific PIPAC method, where the capnoperitoneum is continuously purged by the drug aerosol. In this context, also in-silico analyses by computational fluid dynamic modelling were conducted on the virtual RCP. The physical RCP was used for ex-vivo granulometric analyses concerning drug deposition. Results of RCP qualification show that aerosol deposition in a continuous purged rat capnoperitoneum depends strongly on the position of the inlet and outlet port. Moreover, it could be shown that the droplet size and charge condition of the drug aerosol define the deposition efficiency. In summary, the developed virtual and physical RCP enables detailed in-silico and ex-vivo analyses on drug supply/deposition in rodents.


Asunto(s)
Antineoplásicos/administración & dosificación , Neoplasias Peritoneales/tratamiento farmacológico , Peritoneo/diagnóstico por imagen , Aerosoles , Animales , Antineoplásicos/farmacocinética , Simulación por Computador , Diseño Asistido por Computadora , Humanos , Hidrodinámica , Inyecciones Intraperitoneales/instrumentación , Inyecciones Intraperitoneales/métodos , Modelos Animales , Neoplasias Peritoneales/diagnóstico por imagen , Neoplasias Peritoneales/metabolismo , Peritoneo/metabolismo , Fantasmas de Imagen , Presión , Ratas , Tomografía Computarizada por Rayos X , Interfaz Usuario-Computador
10.
J Am Coll Surg ; 231(6): 704-712, 2020 12.
Artículo en Inglés | MEDLINE | ID: mdl-32891798

RESUMEN

BACKGROUND: In the COVID-19 crisis, laparoscopic surgery is in focus as a relevant source of bioaerosol release. The efficacy of electrostatic aerosol precipitation (EAP) and continuous aerosol evacuation (CAE) to eliminate bioaerosols during laparoscopic surgery was verified. STUDY DESIGN: Ex-vivo laparoscopic cholecystectomies (LCs) were simulated ± EAP or CAE in Pelvitrainer equipped with swine gallbladders. Release of bioaerosols was initiated by performing high-frequency electrosurgery with a monopolar electro hook (MP-HOOK) force at 40 watts (MP-HOOK40) and 60 watts (MP-HOOK60), as well as by ultrasonic cutting (USC). Particle number concentrations (PNC) of arising aerosols were analyzed with a condensation particle counter (CPC). Aerosol samples were taken within the Pelvitrainer close to the source, outside the Pelvitrainer at the working trocar, and in the breathing zone of the surgeon. RESULTS: Within the Pelvitrainer, MP-HOOK40 (6.4 × 105 cm-3) and MP-HOOK60 (7.3 × 105 cm-3) showed significantly higher median PNCs compared to USC (4.4 × 105 cm-3) (p = 0.001). EAP led to a significant decrease of the median PNCs in all 3 groups. A high linear correlation with Pearson correlation coefficients of 0.852, 0.825, and 0.759 were observed by comparing MP-HOOK40 (± EAP), MP-HOOK60 (± EAP), and USC (± EAP), respectively. During ex-vivo LC and CAE, significant bioaerosol contaminations of the operating room occurred. Ex-vivo LC with EAP led to a considerable reduction of the bioaerosol concentration. CONCLUSIONS: EAP was found to be efficient for intraoperative bioaerosol elimination and reducing the risk of bioaerosol exposure for surgical staff.


Asunto(s)
Aerosoles , Colecistectomía Laparoscópica/métodos , Electrocirugia/métodos , Control de Infecciones/métodos , Transmisión de Enfermedad Infecciosa de Paciente a Profesional/prevención & control , Modelos Animales , Electricidad Estática , Aerosoles/análisis , Microbiología del Aire , Animales , COVID-19/prevención & control , COVID-19/transmisión , Colecistectomía Laparoscópica/instrumentación , Electrocirugia/instrumentación , Técnicas In Vitro , Control de Infecciones/instrumentación , Exposición Profesional/análisis , Exposición Profesional/prevención & control , Proyectos Piloto , Porcinos
11.
Light Sci Appl ; 9: 21, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32128161

RESUMEN

Light scattering is a fundamental property that can be exploited to create essential devices such as particle analysers. The most common particle size analyser relies on measuring the angle-dependent diffracted light from a sample illuminated by a laser beam. Compared to other non-light-based counterparts, such a laser diffraction scheme offers precision, but it does so at the expense of size, complexity and cost. In this paper, we introduce the concept of a new particle size analyser in a collimated beam configuration using a consumer electronic camera and machine learning. The key novelty is a small form factor angular spatial filter that allows for the collection of light scattered by the particles up to predefined discrete angles. The filter is combined with a light-emitting diode and a complementary metal-oxide-semiconductor image sensor array to acquire angularly resolved scattering images. From these images, a machine learning model predicts the volume median diameter of the particles. To validate the proposed device, glass beads with diameters ranging from 13 to 125 µm were measured in suspension at several concentrations. We were able to correct for multiple scattering effects and predict the particle size with mean absolute percentage errors of 5.09% and 2.5% for the cases without and with concentration as an input parameter, respectively. When only spherical particles were analysed, the former error was significantly reduced (0.72%). Given that it is compact (on the order of ten cm) and built with low-cost consumer electronics, the newly designed particle size analyser has significant potential for use outside a standard laboratory, for example, in online and in-line industrial process monitoring.

12.
Nanoscale ; 11(38): 17637-17654, 2019 Oct 03.
Artículo en Inglés | MEDLINE | ID: mdl-31539006

RESUMEN

The project nanoGRAVUR (BMBF, 2015-2018) developed a framework for grouping of nanomaterials. Different groups may result for each of the three distinct perspectives of occupational, consumer and environmental safety. The properties, methods and descriptors are harmonised between the three perspectives and are based on: Tier 1 intrinsic physico-chemical properties (what they are) or GHS classification of the non-nano-form (human tox, ecotox, physical hazards); Tier 2 extrinsic physico-chemical properties, release from nano-enabled products, in vitro assays with cells (where they go; what they do); Tier 3 case-specific tests, potentially in vivo studies to substantiate the similarity within groups or application-specific exposure testing. Amongst all properties, dissolution and transformation are least modulated by different nanoforms within one substance, whereas dustiness, dispersion stability, abiotic and especially in vitro surface reactivity vary more often between different nanoforms. The methods developed or selected by nanoGRAVUR fill several gaps highlighted in the ProSafe reviews, and are useful to implement (i) the concept of nanoforms of the European Chemicals Agency (ECHA) and (ii) the concept of discrete forms of the United States Environmental Protection Agency (EPA). One cannot assess the significance of a dissimilarity, if the dynamic range of that property is unknown. Benchmark materials span dynamic ranges that enable us to establish bands, often with order-of-magnitude ranges. In 34 case studies we observed high biological similarity within each substance when we compared different (nano)forms of SiO2, BaSO4, kaolin, CeO2, ZnO, organic pigments, especially when we compared forms that are all untreated on the surface. In contrast, different Fe2O3 or TiO2 (nano)forms differ more significantly. The same nanoforms were also integrated in nano-enabled products (NEPs) for automotive coatings, clinker-reduced cements, cosmetic sunscreen, and lightweight polymers.

13.
Nanomaterials (Basel) ; 9(6)2019 May 31.
Artículo en Inglés | MEDLINE | ID: mdl-31159329

RESUMEN

Dynamic light scattering (DLS) is commonly used for the determination of average particle diameters and suspension stability and popular in academics and industry. However, DLS is not considered suitable for polydisperse samples. The presence of little quantities of micrometre particles in nano and submicrometre suspensions especially affect the reliability of DLS results. Microfiltration might be a suitable method for the removal of unwanted large particles. This study investigates the effect of microfiltration on the diameter distributions as measured by DLS. Polystyrene standards (40-900 nm diameter), and monomodal silica suspensions were filtered with polytetrafluoroethylene (PTFE) membranes (0.1-1.0 µm pore size) to investigate retention properties and grade efficiency. Non-ideal materials were used to prove the results. Experiments showed that a mono-exponential decay can be achieved by filtration. A size safety factor of at least three between labeled pore size and average diameter was found to keep separation as low as possible. Filtration in order to enhance DLS for particulate submicrometre materials was considered suitable for narrowly distributed coated titania and kaolin powder. In a regulatory context, this might have an impact on considering a substance false positive or false negative according to the European Commission (EC) recommendation of a definition of the term nanomaterial.

14.
Nanomaterials (Basel) ; 9(1)2018 Dec 22.
Artículo en Inglés | MEDLINE | ID: mdl-30583541

RESUMEN

Synthetic amorphous silica (SAS) constitute a large group of industrial nanomaterials (NM). Based on their different production processes, SAS can be distinguished as precipitated, fumed, gel and colloidal. The biological activity of SAS, e.g., cytotoxicity or inflammatory potential in the lungs is low but has been shown to depend on the particle size, at least for colloidal silica. Therefore, the preparation of suspensions from highly aggregated or agglomerated SAS powder materials is critical. Here we analyzed the influence of ultrasonic dispersion energy on the biologic activity of SAS using NR8383 alveolar macrophage (AM) assay. Fully characterized SAS (7 precipitated, 3 fumed, 3 gel, and 1 colloidal) were dispersed in H2O by stirring and filtering through a 5 µm filter. Aqueous suspensions were sonicated with low or high ultrasonic dispersion (USD) energy of 18 or 270 kJ/mL, respectively. A dose range of 11.25⁻90 µg/mL was administered to the AM under protein-free conditions to detect particle-cell interactions without the attenuating effect of proteins that typically occur in vivo. The release of lactate dehydrogenase (LDH), glucuronidase (GLU), and tumor necrosis factor α (TNF) were measured after 16 h. Hydrogen peroxide (H2O2) production was assayed after 90 min. The overall pattern of the in vitro response to SAS (12/14) was clearly dose-dependent, except for two SAS which showed very low bioactivity. High USD energy gradually decreased the particle size of precipitated, fumed, and gel SAS whereas the low adverse effect concentrations (LOECs) remained unchanged. Nevertheless, the comparison of dose-response curves revealed slight, but uniform shifts in EC50 values (LDH, and partially GLU) for precipitated SAS (6/7), gel SAS (2/3), and fumed SAS (3/3). Release of TNF changed inconsistently with higher ultrasonic dispersion (USD) energy whereas the induction of H2O2 was diminished in all cases. Electron microscopy and energy dispersive X-ray analysis showed an uptake of SAS into endosomes, lysosomes, endoplasmic reticulum, and different types of phagosomes. The possible effects of different uptake routes are discussed. The study shows that the effect of increased USD energy on the in vitro bioactivity of SAS is surprisingly small. As the in vitro response of AM to different SAS is highly uniform, the production process per se is of minor relevance for toxicity.

15.
Nanomaterials (Basel) ; 8(7)2018 Jun 21.
Artículo en Inglés | MEDLINE | ID: mdl-29933581

RESUMEN

The granulometric characterization of synthetic amorphous silica (SAS) nanomaterials (NMs) still demands harmonized standard operation procedures. SAS is produced as either precipitated, fumed (pyrogenic), gel and colloidal SAS and these qualities differ, among others, with respect to their state of aggregation and aggregate strength. The reproducible production of suspensions from SAS, e.g., for biological testing purposes, demands a reasonable amount of dispersing energy. Using materials representative for each of the types of SAS, we employed ultrasonic dispersing (USD) at energy densities of 8⁻1440 J/mL and measured resulting particle sizes by dynamic light scattering and laser diffraction. In this energy range, USD had no significant impact on particle size distributions of colloidal and gel SAS, but clearly decreased the particle size of precipitated and fumed SAS. For high energy densities, we observed a considerable contamination of SAS suspensions with metal particles caused by abrasion of the sonotrode’s tip. To avoid this problem, the energy density was limited to 270 J/mL and remaining coarse particles were removed with size-selective filtration. The ultrasonic dispersion of SAS at medium levels of energy density is suggested as a reasonable compromise to produce SAS suspensions for toxicological in vitro testing.

16.
Beilstein J Nanotechnol ; 8: 1774-1785, 2017.
Artículo en Inglés | MEDLINE | ID: mdl-28904839

RESUMEN

Dimensional measurements on nano-objects by atomic force microscopy (AFM) require samples of safely fixed and well individualized particles with a suitable surface-specific particle number on flat and clean substrates. Several known and proven particle preparation methods, i.e., membrane filtration, drying, rinsing, dip coating as well as electrostatic and thermal precipitation, were performed by means of scanning electron microscopy to examine their suitability for preparing samples for dimensional AFM measurements. Different suspensions of nano-objects (with varying material, size and shape) stabilized in aqueous solutions were prepared therefore on different flat substrates. The drop-drying method was found to be the most suitable one for the analysed suspensions, because it does not require expensive dedicated equipment and led to a uniform local distribution of individualized nano-objects. Traceable AFM measurements based on Si and SiO2 coated substrates confirmed the suitability of this technique.

17.
Beilstein J Nanotechnol ; 8: 2729-2740, 2017.
Artículo en Inglés | MEDLINE | ID: mdl-29354344

RESUMEN

Background: The delivery of aerosolised chemotherapeutic substances into pressurised capnoperitonea has been reported to be more effective than conventional liquid chemotherapy for the treatment of peritoneal carcinomatosis. However, recent reports reveal limitations of the currently available technology. Material and Methods: A novel approach for pressurised intraperitoneal aerosol chemotherapy (PIPAC), called hyperthermic intracavitary nanoaerosol therapy (HINAT), based on extracavitary generation of hyperthermic and unipolar charged aerosols, was developed. The aerosol size distribution, the spatial drug distribution and in-tissue depth penetration of HINAT were studied by laser diffraction spectrometry, differential electrical mobility analysis, time of flight spectrometry, scintigraphic peritoneography and fluorescence microscopy. All experiments were performed contemporaneous with conventional PIPAC for the purpose of comparison. Furthermore, a first proof of concept was simulated in anesthetised German Landrace pigs. Results: HINAT provides a nanometre-sized (63 nm) unipolar-charged hyperthermic (41 °C) drug aerosol for quasi uniform drug deposition over the whole peritoneum with significantly deeper drug penetration than that offered by conventional PIPAC.

18.
Surg Endosc ; 31(4): 1778-1784, 2017 04.
Artículo en Inglés | MEDLINE | ID: mdl-27631320

RESUMEN

BACKGROUND: Pressurized intraperitoneal aerosol chemotherapy (PIPAC) is gaining acceptance in clinical practice, but detailed information about the microinjection pump (MIP®), the generated aerosol and drug distribution is missing. ANALYTICAL METHODS: Ex vivo granulometric analyses by means of laser diffraction spectrometry were performed for MIP® aerosol characterization. Beside the standard operation conditions, the impact of the volumetric liquid flow rate on the aerosol characteristics was investigated with different liquids. Granulometric results as well as the local drug distribution were verified by ex vivo gravimetric analyses. On the basis of determined MIP® characteristics, the aerosol droplet size, which is necessary for a homogenous intra-abdominal drug distribution, was calculated. RESULTS: Granulometric analyses showed that the MIP® aerosol consists of a bimodal volume-weighted particle size distribution (PSD3) with a median droplet diameter of x 50,3 = 25 µm. Calculations reveal that the droplet size for a homogenous intra-abdominal drug distribution during PIPAC therapy should be below 1.2 µm. We show that >97.5 vol% of the aerosolized liquid is delivered as droplets with ≥3 µm in diameter, which are primarily deposited on the surface beneath the MIP® by gravitational settling and inertial impaction. These findings were confirmed by ex vivo gravimetric analyses, where more than 86.0 vol% of the aerosolized liquid was deposited within a circular area with a diameter of 15 cm. CONCLUSIONS: The granulometric aerosol properties, as well as the aerodynamic conditions achieved by standard MIP® operation, do not support the idea of widespread or homogenous drug distribution in the abdominal cavity.


Asunto(s)
Aerosoles/administración & dosificación , Bombas de Infusión , Microinyecciones/instrumentación , Aerosoles/química , Humanos , Técnicas In Vitro , Inyecciones Intraperitoneales , Presión
19.
J Environ Manage ; 157: 230-7, 2015 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-25910977

RESUMEN

Nanomaterials are commonly used in everyday life products and during their life cycle they can be released into the environment. Soils and sediments are estimated as significant sinks for those nanomaterials. To investigate and assess the behaviour of nanomaterials in soils and sediments standardized test methods are needed. In this study the applicability of two existing international standardized test guidelines for the testing of nanomaterials, OECD TG 106 "Adsorption/Desorption using a Bath Equilibrium Method" and the OECD TG 312 "Leaching in Soil Columns", were investigated. For the study one coated and two uncoated TiO2 nanomaterials were used, respectively. The results indicate that the OECD TG 106 is not applicable for nanomaterials. However, the test method according to OECD TG 312 was found to be applicable if nano-specific adaptations are applied. The mobility investigations of the OECD TG 312 indicated a material-dependent mobility of the nanomaterials, which in some cases may lead to an accumulation in the upper soil layers. Whereas no significant transport was observed for the uncoated materials for the double-coated material (coating with dimethicone and aluminiumoxide) a significant transport was detected and attributed to the coating.


Asunto(s)
Contaminantes del Suelo/química , Titanio/química , Política Ambiental , Humanos , Nanoestructuras/química , Organización para la Cooperación y el Desarrollo Económico , Pruebas de Toxicidad/normas
20.
Beilstein J Nanotechnol ; 6: 2423-30, 2015.
Artículo en Inglés | MEDLINE | ID: mdl-26734533

RESUMEN

The effectiveness of photocatalytic materials increases with the specific surface area, thus nanoscale photocatalyst particles are preferred. However, such nanomaterials are frequently found in an aggregated state, which may reduce the photocatalytic activity due to internal obscuration and the extended diffusion path of the molecules to be treated. This paper investigates the effect of aggregate size on the photocatalytic activity of pyrogenic titania (Aeroxide(®) P25, Evonik), which is widely used in fundamental photocatalysis research. Well-defined and reproducible aggregate sizes were achieved by ultrasonic dispersion. The photocatalytic activity was examined by the color removal of methylene blue (MB) with a laboratory-scale setup based on a plug flow reactor (PFR) and planar UV illumination. The process parameters such as flow regime, optical path length and UV intensity are well-defined and can be varied. Our results firstly show that a complete dispersion of the P25 aggregates is not practical. Secondly, the photocatalytic activity is not further increased beyond a certain degree of dispersion, which probably corresponds to a critical size for which UV irradiation can penetrate the aggregate without significant obscuration.

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