Pharmacokinetics of PEGylated Gold Nanoparticles: In Vitro—In Vivo Correlation

Data suitable for assembling a physiologically-based pharmacokinetic (PBPK) model for nanoparticles (NPs) remain relatively scarce. Therefore, there is a trend in extrapolating the results of in vitro and in silico studies to in vivo nanoparticle hazard and risk assessment. To evaluate the reliability of such approach, a pharmacokinetic study was performed using the same polyethylene glycol-coated gold nanoparticles (PEG-AuNPs) in vitro and in vivo. As in vitro models, human cell lines TH1, A549, Hep G2, and 16HBE were employed. The in vivo PEG-AuNP biodistribution was assessed in rats. The internalization and exclusion of PEG-AuNPs in vitro were modeled as first-order rate processes with the partition coefficient describing the equilibrium distribution. The pharmacokinetic parameters were obtained by fitting the model to the in vitro data and subsequently used for PBPK simulation in vivo. Notable differences were observed in the internalized amount of Au in individual cell lines compared to the corresponding tissues in vivo, with the highest found for renal TH1 cells and kidneys. The main reason for these discrepancies is the absence of natural barriers in the in vitro conditions. Therefore, caution should be exercised when extrapolating in vitro data to predict the in vivo NP burden and response to exposure

A Fiber-Optic Fluorescence Microscope Using a Consumer-Grade Digital Camera for In Vivo Cellular Imaging

BACKGROUND: Early detection is an essential component of cancer management. Unfortunately, visual examination can often be unreliable, and many settings lack the financial capital and infrastructure to operate PET, CT, and MRI systems. Moreover, the infrastructure and expense associated with surgical biopsy and microscopy are a challenge to establishing cancer screening/early detection programs in low-resource settings. Improvements in performance and declining costs have led to the availability of optoelectronic components, which can be used to develop low-cost diagnostic imaging devices for use at the point-of-care. Here, we demonstrate a fiber-optic fluorescence microscope using a consumer-grade camera for in vivo cellular imaging. METHODS: The fiber-optic fluorescence microscope includes an LED light, an objective lens, a fiber-optic bundle, and a consumer-grade digital camera. The system was used to image an oral cancer cell line labeled with 0.01% proflavine. A human tissue specimen was imaged following surgical resection, enabling dysplastic and cancerous regions to be evaluated. The oral mucosa of a healthy human subject was imaged in vivo, following topical application of 0.01% proflavine. FINDINGS: The fiber-optic microscope resolved individual nuclei in all specimens and tissues imaged. This capability allowed qualitative and quantitative differences between normal and precancerous or cancerous tissues to be identified. The optical efficiency of the system permitted imaging of the human oral mucosa in real time. CONCLUSION: Our results indicate this device as a useful tool to assist in the identification of early neoplastic changes in epithelial tissues. This portable, inexpensive unit may be particularly appropriate for use at the point-of-care in low-resource settings

Microfluidic In Vitro Platform for (Nano)Safety and (Nano)Drug Efficiency Screening

Microfluidic technology is a valuable tool for realizing more in vitro models capturing cellular and organ level responses for rapid and animal‐free risk assessment of new chemicals and drugs. Microfluidic cell‐based devices allow high‐throughput screening and flexible automation while lowering costs and reagent consumption due to their miniaturization. There is a growing need for faster and animal‐free approaches for drug development and safety assessment of chemicals (Registration, Evaluation, Authorisation and Restriction of Chemical Substances, REACH). The work presented describes a microfluidic platform for in vivo‐like in vitro cell cultivation. It is equipped with a wafer‐based silicon chip including integrated electrodes and a microcavity. A proof‐of‐concept using different relevant cell models shows its suitability for label‐free assessment of cytotoxic effects. A miniaturized microscope within each module monitors cell morphology and proliferation. Electrodes integrated in the microfluidic channels allow the noninvasive monitoring of barrier integrity followed by a label‐free assessment of cytotoxic effects. Each microfluidic cell cultivation module can be operated individually or be interconnected in a flexible way. The interconnection of the different modules aims at simulation of the whole‐body exposure and response and can contribute to the replacement of animal testing in risk assessment studies in compliance with the 3Rs to replace, reduce, and refine animal experiments

A tree - ring reconstruction of geomorphologic disturbances in cliff forests in the Tatra Mts.

Geomorphological events are very important disturbance factors for cliff forests and forests located on steep mountain slopes. In this study we present dendrochronological reconstruction of two types of disturbances which affect subalpine forest growing in such extreme habitats in Roztoka Valley in the Tatra Mountains: landslide and rockfalls. We determine the years of death of trees found in landslide area on Czuba Roztocka which indicate the year of 1997 as the time of this event, probably related to heavy midsummer rainfall in this year. Scars on trees growing at the base of Orle Ściany cliff allowed determining the rockfall events. We found that scars, even in neighbour trees were formed in different years between 1940 and 2004. It means that they were formed rather by separate stones which fell from the cliff sporadically then a large scale fall of debris at the same time. This may suggest that rockfalls in cliffs of Orle Ściany were limited to single rocks which fell successively when erosion process separated them from the bedrock. Dendrochronology seems to be an effective method which enables long term reconstruction of gemorphological processes in the High Tatras

Estimation of the curing rate of acrylamide used as a consolidant in heritage sandstone conservation

An investigation of the curing (polymerisation) rate of acrylamide was carried out using isothermal and non-isothermal DSC in order to estimate the time for complete conversion of monomer at ambient temperatures. The non-isothermal data were used to model the rate using integral isoconversional and incremental isoconversional kinetic methods. Applying the equations for integral isoconversional methods and extrapolating to ambient temperatures resulted in non-sensical conversion-time curves, where the time estimated decreased for increasing degree of conversion to be reached. This odd behaviour was attributed to the incorrectness of the integration where the kinetic parameters (e.g. The activation energy) are a function of conversion. The problem was addressed by applying incremental methods which provided more reasonable results as the integration is carried out over small conversion increments where the kinetic parameters are assumed to be constant. Estimates of the conversion were compared to isothermal measurements and, although isothermal DSC produced significant variability in the data, extrapolated estimates from non-isothermal kinetic analysis produced, at best, an upper boundary for the estimation of the time to reach a fixed degree of conversion. © 2014 Akadémiai Kiadó, Budapest, Hungary

Assessment of thermal stability of two N-ethoxyethyl-N-methylpiperidinium borate ionic liquids by non-Arrhenian incremental kinetic method

Thermal stability of two borate-based ionic liquids (ILs) recently proposed as effective additive for high voltage batteries, N-ethoxyethyl-N-methylpiperidinium bis(oxalato)borate (BOB) and N-ethoxyethyl-N-methylpiperidinium difluoro(oxalato)borate (DFOB), was investigated. Thermogravimetry–differential thermal analysis measurements performed under nitrogen at 1, 2, 4, and 7◦C min 1 show gradual mass loss above 220◦C for both compounds. The TG curves were processed by isoconversional kinetic analysis under the assumption of nonArrhenian behavior. The outcome of the analysis suggests that even the initial decomposition stages occur by a complex mechanism, probably via competing evaporation–decomposition paths with relative contributions varying with the heating rate. The service lifetimes estimated by the kinetic analysis result in a stability of DFOB up to 10-times higher than that of BOB in the 25 –125 ◦C range. Further experiments were carried out by the Knudsen effusion mass spectrometry (KEMS) in order to get information on the composition of the vapor phase produced upon heating under effusion conditions. The mass spectra of the vapor phase showed a rapid onset of decomposition at 110 ◦C and 130 ◦C for BOB and DFOB, respectively, with a large release of the ion species with m/q = 98. This decomposition path dominates the simple evaporation to neutral ion pairs, which was none theless observed at m/q = 172 (integer cation). All the results seem to point toward a higher stability of DFOB compared to BOB, most probably due to the charge-stabilizing inductive effect of fluorine atoms

Temperature dependence of activation energy of endothermic processes and related imperfections of non-isothermal kinetic evaluations

Zjištěná závislost mezi aktivační energií a rovnovážnou tepotou musí být vhodně zabudována do základní kinetické rovnice. To je důležité pro endotrmické procesy, které lze realizovat při určitém stupni podchlazení. Lze dokázat vzájemnou provázanost kinetických dat, jako jsou aktivační energie, předexponenciální faktor, rychlost ohřevu a rovnovážné pozadí.The of observed dependences between activation energy and equilibrium temperature of process is sourced by insufficiency of kinetic equation dα/dt = f(α) Z exp(−E/RT) which ensures no regards to the fact that endothermic (i.e. enantiotropic) processes (like melting) can be realized only if equilibrium temperature Teq (e.g. Tmelt for melting) is reached. The imperfection of non-isothermal kinetic evaluations are revealed recalling the habitual cases of Kissinger and Piloyan methods which are ignoring the impact of the Newton cooling laws known for centuries