Abstract
BackgroundAs nanoparticles (NPs) become more prevalent in the pharmaceutical industry, questions have arisen from both industry and regulatory stakeholders about the long term effects of these materials. This study was designed to evaluate whether gold (10 nm), silver (50 nm), or silica (10 nm) nanoparticles administered intravenously to mice for up to 8 weeks at doses known to be sub-toxic (non-toxic at single acute or repeat dosing levels) and clinically relevant could produce significant bioaccumulation in liver and spleen macrophages.ResultsRepeated dosing with gold, silver, and silica nanoparticles did not saturate bioaccumulation in liver or spleen macrophages. While no toxicity was observed with gold and silver nanoparticles throughout the 8 week experiment, some effects including histopathological and serum chemistry changes were observed with silica nanoparticles starting at week 3. No major changes in the splenocyte population were observed during the study for any of the nanoparticles tested.ConclusionsThe clinical impact of these changes is unclear but suggests that the mononuclear phagocytic system is able to handle repeated doses of nanoparticles.
Highlights
As nanoparticles (NPs) become more prevalent in the pharmaceutical industry, questions have arisen from both industry and regulatory stakeholders about the long term effects of these materials
The weight concentration in g/L for each lot of NPs stock solutions in water was initially determined by thermal gravimetric analysis (TGA) (TA Instruments). 25 μL of stock solution was placed in the TGA pan and heated from ambient temperature at a rate of 2 °C/min
SiO2 NPs had a Zave of ~24 nm and a Transmission electron microscopy (TEM) ave. of ~11 nm. Both Gold nanoparticles (AuNPs) and SiO2 NPs indicated some agglomeration as evidenced by Dynamic light scattering (DLS) (Fig. 1a, c, respectively)
Summary
As nanoparticles (NPs) become more prevalent in the pharmaceutical industry, questions have arisen from both industry and regulatory stakeholders about the long term effects of these materials. Weaver et al Particle and Fibre Toxicology (2017) 14:25 system (MPS), which is more prevalent in specific tissues (e.g. liver, spleen, lung and bone marrow) [4, 5]. Such accumulation is largely size independent and occurs both in the presence or absence of NP surface coatings (note that which tissues within the MPS that the NPs accumulate may vary by size and surface coatings) [6,7,8]. Once in the MPS organs, the durable NPs remain there, or have protracted elimination [11, 12] With such biopersistence, exposure to the NPs may last years and potentially span the lifetime of the patient. This exposure is especially important in the treatment of chronic diseases where therapies are administered repeatedly to the affected population, with the potential for increased accumulation over the course of treatment
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