Blood Clearance, Distribution, Transformation, Excretion, and Toxicity of Near-Infrared Quantum Dots Ag2Se in Mice.

As a novel fluorescent probe in the second near-infrared window, Ag2Se quantum dots (QDs) exhibit great prospect in in vivo imaging due to their maximal penetration depth and negligible background. However, the in vivo behavior and toxicity of Ag2Se QDs still largely remain unknown, which severely hinders their wide-ranging biomedical applications. Herein, we systematically studied the blood clearance, distribution, transformation, excretion, and toxicity of polyethylene glycol (PEG) coated Ag2Se QDs in mice after intravenous administration with a high dose of 8 µmol/kg body weight. QDs are quickly cleared from the blood with a circulation half-life of 0.4 h. QDs mainly accumulate in liver and spleen and are remarkably transformed into Ag and Se within 1 week. Ag is excreted from the body readily through both feces and urine, whereas Se is excreted hardly. The toxicological evaluations demonstrate that there is no overt acute toxicity of Ag2Se QDs to mice. Moreover, in regard to the in vivo stability problem of Ag2Se QDs, the biotransformation and its related metabolism are intensively discussed, and some promising coating means for Ag2Se QDs to avert transformation are proposed as well. Our work lays a solid foundation for safe applications of Ag2Se QDs in bioimaging in the future.

Synaptic degeneration in rat brain after prolonged oral exposure to silver nanoparticles.

Neurotoxicity of silver nanoparticles has been confirmed in both in vitro and in vivo studies. However, the mechanisms of the toxic action have not been fully clarified. Since nanoparticles are likely to have the ability to enter the brain and significantly accumulate in this organ, it is important to investigate their neurotoxic mechanisms. Here we examine the effect of prolonged exposure of rats to small (10nm) citrate-stabilized silver nanoparticles (as opposed to the ionic silver) on synapse ultrastructure and specific proteins. Administration of both nanosilver and ionic silver over a two-week period resulted in ultrastructural changes including blurred synapse structure and strongly enhanced density of synaptic vesicles clustering in the center of the presynaptic part. Disturbed synaptic membrane leading to liberation of synaptic vesicles into neuropil, which testifies for strong synaptic degeneration, was characteristic feature observed under AgNPs exposure. Also a noteworthy finding was the presence of myelin-like structures derived from fragmented membranes and organelles which are associated with neurodegenerative processes. Additionally, we observed significantly decreased levels of the presynaptic proteins synapsin I and synaptophysin, as well as PSD-95 protein which is an indicator of postsynaptic densities. The present study demonstrates that exposure of adult rats to both forms of silver leads to ultrastructural changes in synapses. However, it seems that small AgNPs lead to more severe synaptic degeneration, mainly in the hippocampal region of brain. The observations may indicate impairment of nerve function and, in the case of hippocampus, may predict impairment of cognitive processes.

Transdermal uptake and organ distribution of silver from two different wound dressings in rats after a burn trauma.

Silver-containing wound dressings are an integral part of wound therapy in adult and pediatric burn patients. The antimicrobial effect of silver is well known and has been described in numerous studies. Side effects are rarely reported from silver-containing wound care products, even though systemic absorption of silver has been shown by elevated levels of silver in the blood of patients after silver exposure during wound therapy. This animal study investigated the silver levels of blood and in which organs and tissues silver is detectable after long-term application of silver-containing wound dressings after a burn trauma. In male rats, a major full-thickness scald was created on their backs according to a standardized burn model. Two different silver-containing wound dressings (nanocrystalline silver [NCS] and silver sulphate foam [SSF]) were applied initially and changed every 7 days. Weekly blood drawings revealed an increase of blood silver in week three with significant higher values in the SSF compared with NCS group (Ag µg/kg 135.8 vs. 61.7; means; p ≤ 0.05). Thereafter, the NCS group showed significantly higher blood silver levels than the SSF group at week five (Ag µg/kg 192.3 vs. 81.3; means; p ≤ 0.01) and six (Ag µg/kg 168.2 vs. 32.9; means; p ≤ 0.01). After 6 weeks, the animals were sacrificed, and the organs and tissues were analyzed for their silver content by inductively coupled plasma mass-spectrometry. Silver was detectable in all analyzed organs and tissue samples, with higher silver values in parenchymatous organs in the NCS than SSF group (Ag µg/kg; spleen: 3,469 vs. 260; kidney: 3,186 vs. 289; liver: 2,022 vs. 313; means; p ≤ 0.05). Silver was also detectable in brain, testis, lung, heart, and muscle tissue.

Optical coherence tomography findings in ocular argyrosis.

A 68-year-old Caucasian man with a remote history of daily colloidal silver ingestion presented for ophthalmic examination in which he was noted to have a distinct slate gray skin discoloration. Funduscopy revealed confluent perimacular drusenoid deposits bilaterally, most of which localized at the level of or anterior to the inner segment ellipsoid band by optical coherence tomography (OCT) imaging. Enhanced depth imaging OCT demonstrated marked choroidal thinning. Fluorescein angiogram displayed a dark or silent choroid. Confirmatory serum silver levels were found to be markedly elevated. This report describes a unique geographic maculopathy with large drusenoid deposits anterior to the ellipsoid layer and severe choroidal thinning in association with ocular argyrosis.

Subacute oral toxicity investigation of nanoparticulate and ionic silver in rats.

Subacute toxicity of 14 nm nanoparticulate silver (Ag-NP) stabilised with polyvinylpyrrolidone and ionic silver in the form of silver acetate (Ag-acetate) was investigated in four-week-old Wistar rats. Animals received orally by gavage the following: vehicle control (10 ♀, 6 ♂); Ag-NP at doses: 2.25 (8 ♀), 4.5 (8 ♀) or 9 mg/kg bw/day (10 ♀, 6 ♂); or Ag-acetate 9 mg silver/kg bw/day (8 ♀) for 28 days. Clinical, haematolological and biochemical parameters, organ weights, macro- and microscopic pathological changes were investigated. Caecal bacterial phyla and their silver resistance genes were quantified. For the Ag-NP groups, no toxicological effects were recorded. For Ag-acetate, lower body weight gain (day 4-7, 11-14, 14-16, P < 0.05; overall, day 1-28, P < 0.01), increased plasma alkaline phosphatase (P < 0.05), decreased plasma urea (P < 0.05) and lower absolute (P < 0.01) and relative (P < 0.05) thymus weight were recorded. In conclusion, these findings indicate toxicity of 9 mg/kg bw/day ionic silver but not of an equimolar Ag-NP dose. This is in accordance with previously reported data showing that oral Ag-acetate, in comparison with an equimolar dose of Ag-NP, resulted in higher silver plasma and organ concentrations.

Clinical performance of a new silver dressing, Contreet Foam, for chronic exuding venous leg ulcers.

OBJECTIVE: This study aimed to evaluate the safety and performance of a new sustained silver-releasing dressing, Contreet Foam (Coloplast A/S), in the treatment of moderately to highly exuding chronic venous leg ulcers in which healing is delayed due to the presence of bacteria. METHOD: The clinical performance of Contreet Foam was studied for four weeks in 25 patients with moderately to highly exuding delayed-healing venous leg ulcers. Healing was assessed on a weekly basis with reference to the wound-bed tissue composition, degree of odour and pain, dressing performance and the dressing's effect on the peri-ulcer area. Blood samples were analysed for silver content. RESULTS: Twenty-three out of 25 patients completed the study. One ulcer healed and no wound infections occurred during the study period. A mean 56% reduction in ulcer area (from 15.6 to 6.9 cm2) was recorded during the four weeks, and there was a mean 25% reduction in granulation tissue from dull to healthy after one week. Wound odour reduced significantly after one week. Mean dressing wear time was 3.1 days, and there were only minimal incidences of leakage. Serum silver levels did not exceed reference values. CONCLUSION: Contreet Foam was found to be safe and performed well when used in the treatment of delayed-healing chronic venous leg ulcers, combining effective antibacterial properties with excellent exudate management. DECLARATION OF INTEREST: This study was supported by Coloplast A/S, Humlebaek, Denmark.