The study on wave run-up roughness and permeability coefficient of stepped slope dike

In this paper, a special kind of revetment stepped revetment which is a new roughening method-is discussed. And this paper studies the different influence of step height on wave run-up and wave absorbing characteristic through physical model test. Then the recommended values of different relative step height dikes??? roughness and permeability coefficient are given. The data shows that the roughness and permeability coefficient is\ud about 0.5. The stepped slope dike is with good wave dissipation effect. Then the data shows that the minimum roughness and permeability coefficient exists with the trend of wave run-up first decreasing and then increasing with the increase of relative step height. Thus ,the paper can serve as a reference for the engineering design

The uptake, retention and clearance of drug-loaded dendrimer nanoparticles in astrocytes - electrophysiological quantification

Nanoparticle-based drug delivery systems may impose risks to patients due to potential toxicity associated with lack of clearance from cells or prolonged carrier-cell retention. This work evaluates vesicular cell uptake, retention and the possible transfer of endocytosed methylprednisolone-loaded carboxymethylchitosan/poly(amidoamine) dendrimer nanoparticles (NPs) into secretory vesicles of rat cultured astrocytes. Cells were incubated with NPs and unitary vesicle fusions/fissions with the plasma membrane were monitored employing high resolution membrane capacitance measurements. In NPs-treated cells the frequency of unitary exocytotic events was significantly increased. The presence of NPs also induce an increase in the size of exocytotic vesicles interacting with the plasma membrane, which exhibit transient fusion with prolonged fusion pore dwell-time. Live-cell confocal imaging revealed that once NPs internalize into endocytotic compartments they remain in the cell for 7 days, although a significant proportion of these merge with secretory vesicles destined for exocytosis. Co-localization studies show the route of clearance of NPs from cells via the exocytotic pathway. These findings bring new insight into the understanding of the intracellular trafficking and biological interactions of drug-loaded dendrimer NPs targeting astrocytes.The study was supported by the Slovenian Research Agency (grants P3 310, J3 6790, J3 7605) and the European Science Foundation COST STSM grant attributed to S.R. Cerqueira. The authors would also like to acknowledge the funds from the Portuguese Foundation for Science and Technology (fellowships to S.R.C. SFRH/BD/48406/2008) and the European Union's Seventh Framework Programme (FP7/2007-2013, grant agreement no. REGPOT-CT2012- 316331-POLARIS). J.M.O. also thanks the FCT for the funds provided under the program Investigador FCT (IF/00423/2012 and IF/01285/2015).info:eu-repo/semantics/publishedVersio

Demonstrating approaches to chemically modify the surface of Ag nanoparticles in order to influence their cytotoxicity and biodistribution after single dose acute intravenous administration

With the advance in material science and the need to diversify market applications, silver nanoparticles (AgNPs) are modified by different surface coatings. However, how these surface modifications influence the effects of AgNPs on human health is still largely unknown. We have evaluated the uptake, toxicity and pharmacokinetics of AgNPs coated with citrate, polyethylene glycol, polyvinyl pyrolidone and branched polyethyleneimine (Citrate AgNPs, PEG AgNPs, PVP AgNPs and BPEI AgNPs, respectively). Our results demonstrated that the toxicity of AgNPs depends on the intracellular localization that was highly dependent on the surface charge. BPEI AgNPs ( potential=+46.5mV) induced the highest cytotoxicity and DNA fragmentation in Hepa1c1c7. In addition, it showed the highest damage to the nucleus of liver cells in the exposed mice, which is associated with a high accumulation in liver tissues. The PEG AgNPs ( potential=-16.2mV) showed the cytotoxicity, a long blood circulation, as well as bioaccumulation in spleen (34.33 mu g/g), which suggest better biocompatibility compared to the other chemically modified AgNPs. Moreover, the adsorption ability with bovine serum albumin revealed that the PEG surface of AgNPs has an optimal biological inertia and can effectively resist opsonization or non-specific binding to protein in mice. The overall results indicated that the biodistribution of AgNPs was significantly dependent on surface chemistry: BPEI AgNPs>Citrate AgNPs=PVP AgNPs>PEG AgNPs. This toxicological data could be useful in supporting the development of safe AgNPs for consumer products and drug delivery applications

A multi-center study of their physicochemical characteristics, cell culture and in vivo experiments

PVP-capped silver nanoparticles with a diameter of the metallic core of 70 nm, a hydrodynamic diameter of 120 nm and a zeta potential of −20 mV were prepared and investigated with regard to their biological activity. This review summarizes the physicochemical properties (dissolution, protein adsorption, dispersability) of these nanoparticles and the cellular consequences of the exposure of a broad range of biological test systems to this defined type of silver nanoparticles. Silver nanoparticles dissolve in water in the presence of oxygen. In addition, in biological media (i.e., in the presence of proteins) the surface of silver nanoparticles is rapidly coated by a protein corona that influences their physicochemical and biological properties including cellular uptake. Silver nanoparticles are taken up by cell-type specific endocytosis pathways as demonstrated for hMSC, primary T-cells, primary monocytes, and astrocytes. A visualization of particles inside cells is possible by X-ray microscopy, fluorescence microscopy, and combined FIB/SEM analysis. By staining organelles, their localization inside the cell can be additionally determined. While primary brain astrocytes are shown to be fairly tolerant toward silver nanoparticles, silver nanoparticles induce the formation of DNA double-strand-breaks (DSB) and lead to chromosomal aberrations and sister-chromatid exchanges in Chinese hamster fibroblast cell lines (CHO9, K1, V79B). An exposure of rats to silver nanoparticles in vivo induced a moderate pulmonary toxicity, however, only at rather high concentrations. The same was found in precision-cut lung slices of rats in which silver nanoparticles remained mainly at the tissue surface. In a human 3D triple-cell culture model consisting of three cell types (alveolar epithelial cells, macrophages, and dendritic cells), adverse effects were also only found at high silver concentrations. The silver ions that are released from silver nanoparticles may be harmful to skin with disrupted barrier (e.g., wounds) and induce oxidative stress in skin cells (HaCaT). In conclusion, the data obtained on the effects of this well-defined type of silver nanoparticles on various biological systems clearly demonstrate that cell-type specific properties as well as experimental conditions determine the biocompatibility of and the cellular responses to an exposure with silver nanoparticles

Cloaking nanoparticles with protein corona shield for targeted drug delivery

Targeted drug delivery using nanoparticles can minimize the side effects of conventional pharmaceutical agents and enhance their efficacy. However, translating nanoparticle-based agents into clinical applications still remains a challenge due to the difficulty in regulating interactions on the interfaces between nanoparticles and biological systems. Here, we present a targeting strategy for nanoparticles incorporated with a supramolecularly pre-coated recombinant fusion protein in which HER2-binding affibody combines with glutathione-S-transferase. Once thermodynamically stabilized in preferred orientations on the nanoparticles, the adsorbed fusion proteins as a corona minimize interactions with serum proteins to prevent the clearance of nanoparticles by macrophages, while ensuring systematic targeting functions in vitro and in vivo. This study provides insight into the use of the supramolecularly built protein corona shield as a targeting agent through regulating the interfaces between nanoparticles and biological systems