Invasive candidiasis (IC) remains as a major cause of morbidity and mortality in critically ill patients. Amphotericin B (AmB) is one of the most effective antifungal agents commonly used to treat this infection. However, it induces severe side effects such as nephrotoxicity, cardiac alterations, nausea, fever, and liver damage. The utilization of drug delivery systems has been explored to overcome these limitations. Several AmB lipid formulations have been developed and are currently available in the market. Although they have the ability to reduce the main side effects of free AmB, their high cost, necessity of repeated intravenous injections for successful treatment, and incidence of pulmonary toxicity have limited their use. In the last decades, alginate has gained significant interest in drug delivery applications as a cost-effective strategy to improve the safety and therapeutic effect of toxic drugs. In this work, the clinically relevant drug AmB was encapsulated into alginate microparticles using the emulsification/external gelation method. We hypothesize that this synthesis strategy may positively impact the antifungal efficacy of AmB-loaded MCPs toward Candida albicans cells while reducing the toxicity in human lung cells. To prove this hypothesis, the ability of the microplatform to disrupt the cellular membrane potential was tested and its antifungal effectiveness toward Candida albicans cells was evaluated using the cell counting and plate count methods. Moreover, the toxicity of the microplatform in human lung cells was evaluated using CellTiter 96® AQueous cell viability assay and qualitative diffusion analysis of acridine orange. Our results demonstrated that the platform developed in this work was able to induce antifungal toxicity against Candida albicans yeast cells at the same level of free AmB with minimal toxicity to lung cells, which is one of the main side effects induced by commercial drug delivery systems containing AmB. Overall, our data provides convincing evidence about the effectiveness of the alginate-based microplatform toward Candida albicans cells. In addition, this vehicle may not require several infusions for a successful treatment while reducing the pulmonary toxic effect induced by commercial lipid formulations.
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Bayesian Network Resource for Meta‐Analysis: Cellular Toxicity of Quantum Dots
A web‐based resource for meta‐analysis of nanomaterials toxicity is developed whereby the utility of Bayesian networks (BNs) is illustrated for exploring the cellular toxicity of Cd‐containing quantum dots (QDs). BN models are developed based on a dataset compiled from 517 publications comprising 3028 cell viability data samples and 837 IC50values. BN QD toxicity (BN‐QDTox) models are developed using both continuous (i.e., numerical) and categorical attributes. Using these models, the most relevant attributes identified for correlating IC50are: QD diameter, exposure time, surface ligand, shell, assay type, surface modification, and surface charge, with the addition of QD concentration for the cell viability analysis. Data exploration via BN models further enables identification of possible association rules for QDs cellular toxicity. The BN models as web‐based applications can be used for rapid intelligent query of the available body of evidence for a given nanomaterial and can be readily updated as the body of knowledge expands.
more » « less- NSF-PAR ID:
- 10460072
- Publisher / Repository:
- Wiley Blackwell (John Wiley & Sons)
- Date Published:
- Journal Name:
- Small
- Volume:
- 15
- Issue:
- 34
- ISSN:
- 1613-6810
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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Results To address these issues, we have developed a fully automated, web-based tool called SpheroScan, which uses the deep learning framework called Mask Regions with Convolutional Neural Networks (R-CNN) for image detection and segmentation. To develop a deep learning model that could be applied to spheroid images from a range of experimental conditions, we trained the model using spheroid images captured using IncuCyte Live-Cell Analysis System and a conventional microscope. Performance evaluation of the trained model using validation and test datasets shows promising results.
Conclusion SpheroScan allows for easy analysis of large numbers of images and provides interactive visualization features for a more in-depth understanding of the data. Our tool represents a significant advancement in the analysis of spheroid images and will facilitate the widespread adoption of 3D spheroid models in scientific research. The source code and a detailed tutorial for SpheroScan are available at https://github.com/FunctionalUrology/SpheroScan.
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Next generation displays and lighting applications are increasingly using inorganic quantum dots (QDs) embedded in polymer matrices to impart bright and tunable emission properties. The toxicity of some heavy metals present in commercial QDs ( e.g. cadmium) has, however, raised concerns about the potential for QDs embedded in polymer matrices to be released during the manufacture, use, and end-of-life phases of the material. One important potential release scenario that polymer composites can experience in the environment is photochemically induced matrix degradation. This process is not well understood at the molecular level. To study this process, the effect of an artificially accelerated weathering process on QD–polymer nanocomposites has been explored by subjecting CdSe and CdSe/ZnS QDs embedded in poly(methyl methacrylate) (PMMA) to UVC irradiation in aqueous media. Significant matrix degradation of QD–PMMA was observed along with measurable mass loss, yellowing of the nanocomposites, and a loss of QD fluorescence. While ICP-MS identified the release of ions, confocal laser scanning microscopy and dark-field hyperspectral imaging were shown to be effective analytical techniques for revealing that QD-containing polymer fragments were also released into aqueous media due to matrix degradation. Viability experiments, which were conducted with Shewanella oneidensis MR-1, showed a statistically significant decrease in bacterial viability when the bacteria were exposed to highly degraded QD-containing polymer fragments. Results from this study highlight the need to quantify not only the extent of nanoparticle release from a polymer nanocomposite but also to determine the form of the released nanoparticles ( e.g. ions or polymer fragments).more » « less
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