176 research outputs found
Anonymisierung von Urteilen
Sowohl Rechtswissenschaft und Rechtspraxis, als auch die breite Öffentlichkeit wünschen sich eine vermehrte Publikation von Gerichtsurteilen. Einer der Gründe, welcher vonseiten der Gerichte häufig dagegen vorgebracht wird, ist der hohe Aufwand für die Anonymisierung der Urteile.
Die Beiträge in diesem Buch basieren zum überwiegenden Teil auf Referaten, die im Rahmen eines Workshops zur Urteilsanonymisierung gehalten wurden. Dieser Workshop ist Teil eines Projekts des Vereins eJustice.CH zur Verbesserung der Zugänglichkeit kantonaler Urteile
Targeting Somatostatin Receptors By Functionalized Mesoporous Silica Nanoparticles - Are We Striking Home?
The concept of delivering nanoformulations to desired tissues by means of targeting membrane receptors of high local abundance by ligands anchored to the nanocarrier has gained a lot of attention over the last decade. Currently, there is no unanimous opinion on whether surface functionalization of nanocarriers by targeting ligands translates into any real benefit in terms of pharmacokinetics or treatment outcomes. Having examined the published nanocarriers designed to engage with somatostatin receptors, we realized that in the majority of cases targetability claims were not supported by solid evidence of targeting ligand-targeted receptor coupling, which is the very crux of a targetability concept. Here, we present an approach to characterize targetability of mesoporous silica-based nanocarriers functionalized with ligands of somatostatin receptors. The targetability proof in our case comes from a functional assay based on a genetically-encoded cAMP probe, which allows for real-time capture of receptor activation in living cells, triggered by targeting ligands on nanoparticles. We elaborate on the development and validation of the assay, highlighting the power of proper functional tests in the characterization pipeline of targeted nanoformulations
Designer nanocarriers for navigating the systemic delivery of oncolytic viruses
Nanotechnology is paving the way for new carrier systems designed to overcome the greatest challenges of oncolytic virotherapy; systemic administration and subsequent implications of immune responses and specific cell binding and entry. Systemic administration of oncolytic agents is vital for disseminated neoplasms, however transition of nanoparticles (NP) to virotherapy has yielded modest results. Their success relies on how they navigate the merry-go-round of often-contradictory phases of NP delivery: circulatory longevity, tissue permeation and cellular interaction, with many studies postulating design features optimal for each phase. This review discusses the optimal design of NPs for the transport of oncolytic viruses within these phases, to determine whether improved virotherapeutic efficacy lies in the pharmacokinetic/pharmacodynamics characteristics of the NP–oncolytic viruses complexes rather than manipulation of the virus and targeting ligands
Edible bio-based nanostructures: delivery, absorption and potential toxicity
The development of bio-based nanostructures as nanocarriers of bioactive compounds to specific body sites has been presented as a hot topic in food, pharmaceutical and nanotechnology fields. Food and pharmaceutical industries seek to explore the huge potential of these nanostructures, once they can be entirely composed of biocompatible and non-toxic materials. At the same time, they allow the incorporation of lipophilic and hydrophilic bioactive compounds protecting them against degradation, maintaining its active and functional performance. Nevertheless, the physicochemical properties of such structures (e.g., size and charge) could change significantly their behavior in the gastrointestinal (GI) tract. The main challenges in the development of these nanostructures are the proper characterization and understanding of the processes occurring at their surface, when in contact with living systems. This is crucial to understand their delivery and absorption behavior as well as to recognize potential toxicological effects. This review will provide an insight into the recent innovations and challenges in the field of delivery via GI tract using bio-based nanostructures. Also, an overview of the approaches followed to ensure an effective deliver (e.g., avoiding physiological barriers) and to enhance stability and absorptive intestinal uptake of bioactive compounds will be provided. Information about nanostructures potential toxicity and a concise description of the in vitro and in vivo toxicity studies will also be given.Joana T. Martins, Oscar L. Ramos, Ana C. Pinheiro, Ana I. Bourbon, Helder D. Silva and Miguel A. Cerqueira (SFRH/BPD/89992/2012, SFRH/BPD/80766/2011, SFRH/BPD/101181/2014, SFRH/BD/73178/2010, SFRH/BD/81288/2011, and SFRH/BPD/72753/2010, respectively) are the recipients of a fellowship from the Fundacao para a Ciencia e Tecnologia (FCT, POPH-QREN and FSE, Portugal). The authors thank the FCT Strategic Project PEst-OE/EQB/LA0023/2013 and the project "BioInd-Biotechnology and Bioengineering for improved Industrial and Agro-Food processes," REF.NORTE-07-0124-FEDER-000028, co-funded by the Programa Operacional Regional do Norte (ON.2-O Novo Norte), QREN, FEDER. We also thank to the European Commission: BIOCAPS (316265, FP7/REGPOT-2012-2013.1) and Xunta de Galicia: Agrupamento INBIOMED (2012/273) and Grupo con potencial de crecimiento. The support of EU Cost Action FA1001 is gratefully acknowledged
Silica nanoparticles and their interaction with cells : a multidisciplinary approach
Silica nanoparticles are increasingly used as drug delivery systems and for biomedical imaging.
Therapeutic and diagnostic agents can be incorporated into the silica matrix to improve the stability
and solubility of hydrophobic drugs in biological systems. However, the safety of silica
nanoparticles as drug carriers remains controversial. To date, no validated and accepted nanospecific
tests exist to predict the potentially harmful impact of these materials on the human body.
The mechanism proposed for hemolysis of unmodified silica nanoparticles is based on the electrostatic
interaction between the silanol surface groups and the quaternary ammonium in the choline
head group of the phospholipids. However, a detailed understanding of this process is missing.
In this thesis, different silica nanoparticles where synthesized, characterized, and tested in two cell
lines regarding viability and oxidative stress. Hemolysis was assessed using red blood cells. Furthermore,
the hemolytic mechanism of a chosen silica nanoparticle type was investigated in depth
using a biophysical chemistry approach. We used the dye-leakage assay, isothermal titration
calorimetry, solid state nuclear magnetic resonance, and flow cytometry to elucidate this mechanism.
Our results revealed that silica nanoparticles with a porous surface and negative surface charge
had the strongest impact on viability in a concentration dependent manner. This is in contrast to
non-porous silica nanoparticles. None of the studied particles caused oxidative stress in either cell
lines. Particles with a negative surface charge induced hemolysis. The mechanism responsible for
the hemolysis for silica nanoparticles had no electrostatic component. The nuclear magnetic resonance
data revealed no interaction with the choline group. However, nuclear magnetic resonance
data suggested the presence of faster tumbling species.\ud
Our toxicological and mechanistic studies showed potential hazards of spherical amorphous silica
nanoparticles. Physico-chemical properties mediating toxicity in living cells were identified.
We propose that our standardized silica nanoparticles may serve as a readily available reference
material for nanotoxicological investigations. Mechanistic data did not support an electrostatic
interaction as postulated in the literature, but rather a strong adsorption process that may lead
to hemolysis. Furthermore, the presence of faster tumbling species suggested the formation of
smaller lipid bilayer structures upon silica nanoparticles exposure. Flow cytometry data revealed
that their size is about 100 nm. It remains to be proven if the bilayer wraps around the hemolytic
silica nanoparticles, if an exclusive formation of smaller species without wrapping is present, or
both of the aforementioned
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