Influence of PEG coating on the oral bioavailability of gold nanoparticles in rats

Metallic nanoparticles can be produced in a variety of shapes, sizes, and surface chemistries, making them promising potential tools for drug delivery. Most studies to date have evaluated uptake of metallic nanoparticles from the GI tract with methods that are at best semi-quantitative. This study used the classical method of comparing blood concentration area under the curve (AUC) following intravenous and oral doses to determine the oral bioavailability of 1, 2 and 5 kDa PEG-coated 5 nm gold nanoparticles (AuNPs). Male rats were given a single intravenous dose (0.8 mg/kg) or oral (gavage) dose (8 mg/kg) of a PEG-coated AuNP, and the concentration of gold was measured in blood over time and in tissues (liver, spleen and kidney) at sacrifice. Blood concentrations following oral administration were inversely related to PEG size, and the AUC in blood was significantly greater for the 1 kDa PEG-coated AuNPs than particles coated with 2 or 5 kDa PEG. However, bioavailabilities of all of the particles were very low (< 0.1%). Concentrations in liver, spleen and kidney were similar after the intravenous doses, but kidney showed the highest concentrations after an oral dose. In addition to providing information on the bioavailability of AuNPs coated with PEG in the 1–5 kDa range, this study demonstrates the utility of applying the blood AUC approach to assess the quantitative oral bioavailability of metallic nanoparticles

Evaluation of two-dimensional gray-scale images for microtexture analysis of aggregate surface

A powerful texture feature extraction algorithm based on transform-based analysis of two-dimensional (2D) gray-scale images was employed in the aggregate image measurement system (AIMS) to quantitatively describe aggregate surface microtexture by way of a parameter called texture index (TI). TI has been used successfully to distinguish between unpolished and polished aggregates. The main goal of this research was to further evaluate this system using a broader range of aggregates in terms of mineral composition including highly uniform limestone sources and highly variable granitic sources. Results confirmed that TI successfully distinguished polished from unpolished aggregates for all mineral compositions. However, an excessively broad range of TI values was observed. Specifically, TI values of aggregates with highly variable mineral composition were far greater than any value previously reported in the literature. Interestingly, unusually high TI values were also observed for limestone aggregate particles obtained from field cores. It was hypothesized that nonroughness-related features such as surface color pattern resulting from mineral variation and absorbed asphalt resulted in artificially high TI. Independent experimental roughness evaluation using scanning electron microscopy (SEM) and surfaces prepared to the same roughness level confirmed this hypothesis. The results clearly indicated the need for a change in image acquisition and/or analysis algorithm to exclude the effect of surface color pattern in texture analysis of aggregate surface images

Validated model of platelet slip at stenosis and device surfaces

The article of record as published may be found at https://doi.org/10.1080/09537104.2019.1636021Platelets are central to thrombosis. However, it is unknown whether platelets slip at vascular or device surfaces. The presence of platelet slip at a surface would interrupt physical contact between the platelet and that surface, and therefore diminish adhesion and thrombosis. Unfortunately, no existing technology can directly measure platelet slip in a biological environment. The objective of this study was to explore whether microspheres–modeling platelets–slip at different vascular and device surfaces in an acrylic scaled-up model coronary artery. The microspheres (3.12 µm diameter) were suspended in a transparent glycerol/water experimental fluid, which flowed continuously at Reynolds numbers typical of coronary flow (200–400) through the model artery. We placed a series of axisymmetric acrylic stenoses (cross-sectional area reduction [CSAr], 20–90%) into the model artery, both without and with a central cylinder present (modeling a percutaneous interventional guide wire, and with a scaled-up Doppler catheter mounted upstream). We used laser Doppler velocimetry (LDV) to measure microsphere velocities within, proximal and distal to each stenosis, and compared to computer simulations of fluid flow with no-slip. For validation, we replaced the acrylic with paraffin stenoses (more biologically relevant from a surface roughness perspective)and then analyzed the signal recorded by the scaled-up Doppler catheter. Using the LDV, we identified progressive microsphere slip proportional to CSAr inside entrances for stenoses ≥60% and ≥40% without and with cylinder present, respectively. Additionally, microsphere slip occurred universally along the cylinder surface. Computer simulations indicated increased fluid shear rates (velocity gradients) at these particular locations, and logistic regression analysis comparing microsphere slip with fluid shear rate resulted in a c-index of 0.989 at a cut-point fluid shear rate of (10.61 [cm−1]×mean velocity [cm×sec−1]). Moreover, the presence of the cylinder caused disordering of microsphere shear rates distal to higher grade stenoses, indicating a disturbance in their flow. Finally, despite lower precision, the signal recorded by the scaled-up Doppler catheter nonetheless indicated slip at the entry into and at most locations distal to the 90% stenosis. Our validated model establishes proof of concept for platelet slip, and platelet slip explains several important basic and clinical observations. If technological advances allow confirmation in a true biologic environment, then our results will likely influence the development of shear-dependent antiplatelet drugs. Also, adding shear rate information, our results provide a direct experimental fluid dynamic foundation for antiplatelet-focused antithrombotic therapy during coronary interventions directed towards higher grade atherosclerotic stenoses.This work was supported by: American Heart Association [California Affiliate Grant 88-N7]; North Carolina Research Triangle Nanotechnology Network [Kickstarter Program]. SMIF is a member of the North Carolina Research Triangle Nanotechnology Network (RTNN), which is supported by the National Science Foundation (Grant ECCS-1542015) as part of the National Nanotechnology Coordinated Infrastructure (NNCI)