ABSTRACT
The assessment of the safety of nano-biomedical products for patients is an essential prerequisite for their market authorization. However, it is also required to ensure the safety of the workers who may be unintentionally exposed to the nano-biomaterials (NBMs) in these medical applications during their synthesis, formulation into products and end-of-life processing and also of the medical professionals (e.g., nurses, doctors, dentists) using the products for treating patients. There is only a handful of workplace risk assessments focussing on NBMs used in medical applications. Our goal is to contribute to increasing the knowledge in this area by assessing the occupational risks of magnetite (Fe3O4) nanoparticles coated with PLGA-b-PEG-COOH used as contrast agent in magnetic resonance imaging (MRI) by applying the software-based Decision Support System (DSS) which was developed in the EU H2020 project BIORIMA. The occupational risk assessment was performed according to regulatory requirements and using state-of-the-art models for hazard and exposure assessment, which are part of the DSS. Exposure scenarios for each life cycle stage were developed using data from literature, inputs from partnering industries and results of a questionnaire distributed to healthcare professionals, i.e., physicians, nurses, technicians working with contrast agents for MRI. Exposure concentrations were obtained either from predictive exposure models or monitoring campaigns designed specifically for this study. Derived No-Effect Levels (DNELs) were calculated by means of the APROBA tool starting from in vivo hazard data from literature. The exposure estimates/measurements and the DNELs were used to perform probabilistic risk characterisation for the formulated exposure scenarios, including uncertainty analysis. The obtained results revealed negligible risks for workers along the life cycle of magnetite NBMs used as contrast agent for the diagnosis of tumour cells in all exposure scenarios except in one when risk is considered acceptable after the adoption of specific risk management measures. The study also demonstrated the added value of using the BIORIMA DSS for quantification and communication of occupational risks of nano-biomedical applications and the associated uncertainties.
Subject(s)
Contrast Media , Ferrosoferric Oxide , Contrast Media/adverse effects , Humans , Occupational Exposure , Risk Assessment/methods , Risk Management , WorkplaceABSTRACT
Progress in nanotechnology has determined new strategies concerning drug delivery into the central nervous system for the treatment of degenerative and inflammatory diseases. To date, brain targeting through systemic drug administration, even in a nano-composition, is often unsuccessful. Therefore, we investigated the possibility of loading T lymphocytes with PGLA-PEG COOH magnetite nanoparticles (30 nm), which can be built up to easily bind drugs and monoclonal antibodies, and to exploit the ability of activated T cells to cross the blood-brain barrier and infiltrate the brain parenchyma. Iron oxide nanoparticles have been widely used in biomedical applications due to their theranostic properties and are therefore a well-established nanomaterial. The magnetite core is easily hybridized with polymeric compounds that may enhance the possibility of the nanoparticles entering cells with low phagocytic properties. Taking advantage of these material characteristics, after in vitro assessment of the viability and functionality of nano-loaded MOG35-55 specific T cells, we transferred cells containing the nano-cargo into naïve mice affected by experimental autoimmune encephalomyelitis, an animal model of multiple sclerosis. By means of histological and immunohistological methods, we were able to identify the nano-loaded T cells in the central nervous system. Our data demonstrated that T cells containing nanomaterials hold the possibility of carrying and releasing nanoparticles in the brain.
ABSTRACT
Metal oxide nanoparticles, hybridized with various polymeric chemicals, represent a novel and breakthrough application in drug delivery, hyperthermia treatment and imaging techniques. Radiolabeling of these nanoformulations can result in new and attractive dual-imaging agents as well as provide accurate in vivo information on their biodistribution profile. In this paper a comparison study has been made between two of the most promising hybrid core-shell nanosystems, bearing either magnetite (Fe3O4) or cobalt ferrite (CoFe2O4) cores, regarding their magnetic, radiolabeling, hyperthermic and biodistribution properties. While hyperthermic properties were found to be affected by the metal-core type, the radiolabeling ability and the in vivo fate of the nanoformulations seem to depend critically on the size and the shell composition.
