Dataset Information

Assessment of Cu and CuO nanoparticle ecological responses using laboratory small-scale microcosms.

ABSTRACT: Copper based nanoparticles (NPs) are used extensively in industrial and commercial products as sensors, catalysts, surfactants, antimicrobials, and for other purposes. The high production volume and increasing use of copper-based NPs make their ecological risk a concern. Commonly used copper-based NPs are composed of metallic copper or copper oxide (Cu and CuO NPs); however, their environmental toxicity can vary dramatically depending on their physico-chemical properties, such as dissolution, aggregation behavior, and the generation of reactive oxygen species. Here, we investigated the NP dissolution, organismal uptake and aquatic toxicity of Cu and CuO NPs at 0, 0.1, 1, 5 or 10 mg Cu/L using a previously developed multi-species microcosm. This 5-day microcosm assay was comprised of C. reinhardtti, E. coli, D. magna, and D. rerio. We hypothesized that Cu and CuO NPs can elicit differential toxicity to the organisms due to alterations in particle dissolution and variations in organismal uptake. The actual concentrations of dissolved Cu released from the NPs were compared to ionic copper controls (CuCl2) at the same concentrations to determine the relative contribution of particulate and dissolved Cu on organism uptake and toxicity. We found that both NPs had higher uptake in D. magna and zebrafish than equivalent ionic exposures, suggesting that both Cu-based NPs are taken up by organisms. Cu NP exposures significantly inhibited algal growth rate, D. magna survival, and zebrafish hatching while exposure to equivalent concentrations of CuCl2 (dissolved Cu fraction) and CuO NPs did not. This indicates that Cu NPs themselves likely elicited a particle-specific mechanism of toxicity to the test organisms, or a combination effect from ionic Cu and the Cu NPs. Overall, this work was the first study to utilize a small-scale rapid assay designed to evaluate the fate and ecotoxicological impacts of Cu and CuO NPs in a mixed aquatic community.

SUBMITTER: Wu F

PROVIDER: S-EPMC7211403 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

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Assessment of Cu and CuO nanoparticle ecological responses using laboratory small-scale microcosms.

Wu Fan F Harper Bryan J BJ Crandon Lauren E LE Harper Stacey L SL

Environmental science. Nano 20191120 1

Copper based nanoparticles (NPs) are used extensively in industrial and commercial products as sensors, catalysts, surfactants, antimicrobials, and for other purposes. The high production volume and increasing use of copper-based NPs make their ecological risk a concern. Commonly used copper-based NPs are composed of metallic copper or copper oxide (Cu and CuO NPs); however, their environmental toxicity can vary dramatically depending on their physico-chemical properties, such as dissolution, ag ...[more]

PMID: 32391155

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Project description:BACKGROUND:"Nanomedicine" is the application of purposely designed nano-scale materials for improved therapeutic and diagnostic outcomes, which cannot be otherwise achieved using conventional delivery approaches. While "translation" in drug development commonly encompasses the steps from discovery to human clinical trials, a different set of translational steps is required in nanomedicine. Although significant development effort has been focused on nanomedicine, the translation from laboratory formulations up to large scale production has been one of the major challenges to the success of such nano-therapeutics. In particular, scale-up significantly alters momentum and mass transfer rates, which leads to different regimes for the formation of nanomedicines. Therefore, unlike the conventional definition of translational medicine, a key component of "bench-to-bedside" translational research in nanomedicine is the scale-up of the synthesis and processing of the nano-formulation to achieve precise control of the nanoscale properties. This consistency requires reproducibility of size, polydispersity and drug efficacy. METHODS:Here we demonstrate that Flash NanoPrecipitation (FNP) offers a scalable and continuous technique to scale up the production rate of nanoparticles from a laboratory scale to a pilot scale. FNP is a continuous, stabilizer-directed rapid precipitation process. Lumefantrine, an anti-malaria drug, was chosen as a representative drug that was processed into 200 nm nanoparticles with enhanced bioavailability and dissolution kinetics. Three scales of mixers, including a small-scale confined impinging jet mixer, a mid-scale multi-inlet vortex mixer (MIVM) and a large-scale multi-inlet vortex mixer, were utilized in the formulation. The production rate of nanoparticles was varied from a few milligrams in a laboratory batch mode to around 1 kg/day in a continuous large-scale mode, with the size and polydispersity similar at all scales. RESULTS:Nanoparticles of 200 nm were made at all three scales of mixers by operating at equivalent Reynolds numbers (dynamic similarity) in each mixer. Powder X-ray diffraction and differential scanning calorimetry demonstrated that the drugs were encapsulated in an amorphous form across all production rates. Next, scalable and continuous spray drying was applied to obtain dried powders for long-term storage stability. For dissolution kinetics, spray dried samples produced by the large-scale MIVM showed 100% release in less than 2 h in both fasted and fed state intestinal fluids, similar to small-batch low-temperature lyophilization. CONCLUSIONS:These results validate the successful translation of a nanoparticle formulation from the discovery scale to the clinical scale. Coupling nanoparticle production using FNP processing with spray drying offers a continuous nanofabrication platform to scale up nanoparticle synthesis and processing into solid dosage forms.

Dataset Information

Assessment of Cu and CuO nanoparticle ecological responses using laboratory small-scale microcosms.

Publications

Assessment of Cu and CuO nanoparticle ecological responses using laboratory small-scale microcosms.

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