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European Journal of Pharmaceutical... Sep 2023The in-situ formation of nanoparticles from polymer-based solid medicines, although previously described, has been overlooked despite its potential to interfere with...
The in-situ formation of nanoparticles from polymer-based solid medicines, although previously described, has been overlooked despite its potential to interfere with oral drug bioavailability. Such polymeric pharmaceuticals are becoming increasingly common on the market and can become even more popular due to the dizzying advance of 3D printing medicines. Hence, this work aimed to study this phenomenon during the dissolution of 3D printed tablets produced with three different polymers, hydroxypropylmethylcellulose acetate succinate (HPMCAS), polyvinyl alcohol (PVA), and Eudragit RL PO® (EUD RL) combined with plasticizers and the model drug naringenin (NAR). The components' interaction, dissolution behavior, and characteristics of the formed particles were investigated employing thermal, spectroscopic, mechanical, and chromatographic assays. All the systems generated stable spherical-shaped particles throughout 24 h, encapsulating over 25% of NAR. Results suggest encapsulation efficiencies variations may depend on interactions between polymer-drug, drug-plasticizer, and polymer-plasticizer, which formed stable nanoparticles even in the drug absence, as observed with the HPMCAS and EUD RL formulations. Additionally, components solubility in the medium and previous formulation treatments are also a decisive factor for nanoparticle formation. In particular, the treatment provided by hot-melt extrusion and FDM 3D printing affected the dissolution efficiency enhancing the interaction between the components, reverberating on particle size and particle formation kinetics mainly for HPMCAS and EUD RL. In conclusion, the 3D printing process influences the in-situ formation of nanoparticles, which can directly affect oral drug bioavailability and needs to be monitored.
Topics: Drug Liberation; Plasticizers; Polymers; Solubility; Tablets; Printing, Three-Dimensional; Technology, Pharmaceutical
PubMed: 37406970
DOI: 10.1016/j.ejps.2023.106517 -
Journal of Agricultural and Food... Nov 2023Di-(2-ethylhexyl) phthalate (DEHP) plasticizer, a well-known environmental and food pollutant, has neurotoxicity. However, it is unknown whether DEHP leads to learning...
Di-(2-ethylhexyl) phthalate (DEHP) plasticizer, a well-known environmental and food pollutant, has neurotoxicity. However, it is unknown whether DEHP leads to learning and memory impairment through gut-brain axis and whether can alleviate this impairment. Here, C57BL/6 mice were exposed to DEHP and treated with . Learning and memory abilities were evaluated through the Morris water maze. The levels of synaptic proteins, inflammatory cytokines, and 5-hydroxytryptamine (5-HT) were detected by immunohistochemistry or ELISA. Gut microbiota were analyzed through 16S rRNA sequencing. alleviated DEHP-induced learning and memory impairment and restored synaptic proteins. It significantly relieved DEHP-induced inflammation and recovered 5-HT levels. recovered the richness of the gut microbiota decreased by DEHP, with the genus increasing the most. Overall, alleviated DEHP-induced learning and memory impairment due to reduced inflammation and increased 5-HT secretion, which was partly attributed to the recovery of gut microbiota.
Topics: Mice; Animals; Plasticizers; Diethylhexyl Phthalate; Brain-Gut Axis; Clostridium butyricum; RNA, Ribosomal, 16S; Serotonin; Mice, Inbred C57BL; Inflammation
PubMed: 37963287
DOI: 10.1021/acs.jafc.3c03533 -
Chemosphere May 2024Plastic pollution has become a major global concern, posing numerous challenges for the environment and wildlife. Most conventional ways of plastics degradation are... (Review)
Review
Plastic pollution has become a major global concern, posing numerous challenges for the environment and wildlife. Most conventional ways of plastics degradation are inefficient and cause great damage to ecosystems. The development of biodegradable plastics offers a promising solution for waste management. These plastics are designed to break down under various conditions, opening up new possibilities to mitigate the negative impact of traditional plastics. Microbes, including bacteria and fungi, play a crucial role in the degradation of bioplastics by producing and secreting extracellular enzymes, such as cutinase, lipases, and proteases. However, these microbial enzymes are sensitive to extreme environmental conditions, such as temperature and acidity, affecting their functions and stability. To address these challenges, scientists have employed protein engineering and immobilization techniques to enhance enzyme stability and predict protein structures. Strategies such as improving enzyme and substrate interaction, increasing enzyme thermostability, reinforcing the bonding between the active site of the enzyme and substrate, and refining enzyme activity are being utilized to boost enzyme immobilization and functionality. Recently, bioengineering through gene cloning and expression in potential microorganisms, has revolutionized the biodegradation of bioplastics. This review aimed to discuss the most recent protein engineering strategies for modifying bioplastic-degrading enzymes in terms of stability and functionality, including enzyme thermostability enhancement, reinforcing the substrate binding to the enzyme active site, refining with other enzymes, and improvement of enzyme surface and substrate action. Additionally, discovered bioplastic-degrading exoenzymes by metagenomics techniques were emphasized.
Topics: Plastics; Ecosystem; Biodegradable Plastics; Biopolymers; Biodegradation, Environmental; Bioengineering
PubMed: 38521099
DOI: 10.1016/j.chemosphere.2024.141749 -
Pediatric Research Nov 2023Phthalates exposure might affect children's intelligence development. This study aimed to determine (1) whether sex and age affect cognitive function and (2) whether sex... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Phthalates exposure might affect children's intelligence development. This study aimed to determine (1) whether sex and age affect cognitive function and (2) whether sex differences in cognitive performance are wider with higher phthalate concentrations.
METHODS
Data were collected from PubMed (1998-2022), PROQUEST (1997-2022), and SpringerLink (1995-2022). The study followed the PRISMA process. The included articles were followed by PECO framework. The GRADE applied to assess the certainty of evidence. Of 2422 articles obtained, nine were selected using inclusion criteria. The random-effects model was used to estimate the pooled effects.
RESULTS
Our meta-regression indicated a significant difference between sex differences with age at phthalate concentration assessment (β = -0.25; 95% CI = -0.47, -0.03) and MEHP concentration (β = -0.20; 95% CI = -0.37, -0.03).
CONCLUSIONS
The limitation of the current article is it only provides information on intelligence level rather than other aspects of cognitive function. Thus, the sequelae of phthalate exposure on attention and executive function are still unclear. Our analysis shows significant difference between sex differences in cognitive function scores associated with age at phthalate concentration assessment. Girls might be more resilient in cognitive function at a younger age or during lower concentrations of phthalates metabolites.
IMPACT
This is the first meta-analysis to evaluate the pooled estimates of sex differences in objective cognitive functions among children with phthalate exposure. The female might be a protective factor when exposed to toxic plasticizers while the concentration is low. This study captures the possible role of sex in cognitive functioning and plasticizer exposure through a meta-analysis of children's sex, cognitive scores, and plasticizer exposure.
Topics: Humans; Child; Male; Female; Plasticizers; Sex Characteristics; Cognition; Phthalic Acids; Environmental Exposure; Environmental Pollutants
PubMed: 37264138
DOI: 10.1038/s41390-023-02672-5 -
Environmental Pollution (Barking, Essex... Jun 2024Plastic pollution has spread through all parts of the marine environment, representing a significant threat to species and ecosystems. This study investigates the role... (Meta-Analysis)
Meta-Analysis Review
Plastic pollution has spread through all parts of the marine environment, representing a significant threat to species and ecosystems. This study investigates the role of copepods as widespread microplastic reservoirs in the marine environment, by performing, a systematic review, meta-analysis, and semiquantitative analysis of scientific articles focusing on the interaction between copepods and microplastics under field conditions. Our findings indicate that despite uniformly low ingestion of microplastics across different marine layers and geographical areas, with a slight uptake in neustonic copepods, copepods might constitute one of the largest marine microplastic reservoirs. This phenomenon is attributed more to their vast abundance than to average microplastic ingestion values. In this article, a framework for data analysis and reporting is proposed to facilitate future large-scale evaluations and modelling of their extent and impact on plastic and carbon cycles. These insights place copepods at the forefront of the marine plastic cycle, possibly affecting plastic distribution, and bioavailability, thereby opening new pathways for understanding the complex dynamics of microplastics in marine ecosystems.
Topics: Copepoda; Animals; Microplastics; Water Pollutants, Chemical; Environmental Monitoring; Ecosystem; Plastics
PubMed: 38701964
DOI: 10.1016/j.envpol.2024.124092 -
Environmental Research Nov 2023Exposure to phthalates, adipates, bisphenol-A (BPA), and pesticides may have important health consequences for children, but little is known regarding their presence in...
BACKGROUND
Exposure to phthalates, adipates, bisphenol-A (BPA), and pesticides may have important health consequences for children, but little is known regarding their presence in school meals, a major food source for children. The aims of this study were to determine the presence of phthalates, adipates, BPA, and pesticides in school meals.
METHODS
Using a cross-sectional design, n = 50 school meal components were collected from four school districts in New England (n = 8 elementary/K-8 schools) differing preparation methods (on-site scratch cooking and pre-packaged heat and serve meals with plastic films) between 2019 and 2021. Meal components were tested for the presence of phthalates, adipates, BPA, and pesticides by an independent laboratory.
RESULTS
One adipate, DEHA, was detected in 42% of samples (range 0.08 mg/kg - 50.39 mg/kg). Among the prepackaged foods, DEHA was detected in 86% of samples, which also contained the highest average concentrations among all the samples tested. The phthalate Diisononyl phthalate (DINP) was detected in only one sample, and BPA was not detected in any of the samples tested. Pesticides were detected in 64% of produce and 27% of entrées, but most had levels that were lower than the average levels detected by the USDA's Pesticide Data Program and only one sample had levels that exceeded those detected by the USDA (Cyfluthrin levels in one sample of apples were 0.038 mg/kg compared with an USDA average range of 0.004-0.032 mg/kg).
CONCLUSIONS
Overall pesticides and phthalate levels in school meals are low and BPA was not detected. However, this study suggests that manufacturers may be changing to less studied plasticizers such as DEHA. More studies should examine the impact of DEHA on human health, particularly among children. As schools transition back from the COVID-19 pandemic, foods packaged in plastic should be minimized where possible. Overall, school meals remain one of the healthiest options for children and policies that support on site cooking can further strengthen the quality of school meals.
Topics: Child; Humans; Pesticides; Cross-Sectional Studies; Pandemics; COVID-19; Phthalic Acids; Plasticizers; Adipates; Meals
PubMed: 37442262
DOI: 10.1016/j.envres.2023.116632 -
Environment International Jan 2024Due to their exceptional properties and cost effectiveness, polyamides or nylons have emerged as widely used materials, revolutionizing diverse industries, including...
Due to their exceptional properties and cost effectiveness, polyamides or nylons have emerged as widely used materials, revolutionizing diverse industries, including industrial 3D printing or additive manufacturing (AM). Powder-based AM technologies employ tonnes of polyamide microplastics to produce complex components every year. However, the lack of comprehensive toxicity assessment of particulate polyamides and polyamide-associated chemicals, especially in the light of the global microplastics crisis, calls for urgent action. This study investigated the physicochemical properties of polyamide-12 microplastics used in AM, and assessed a number of toxicity endpoints focusing on inflammation, immunometabolism, genotoxicity, aryl hydrocarbon receptor (AhR) activation, endocrine disruption, and cell morphology. Specifically, microplastics examination by means of field emission scanning electron microscopy revealed that work flow reuse of material created a fraction of smaller particles with an average size of 1-5 µm, a size range readily available for uptake by human cells. Moreover, chemical analysis by means of gas chromatography high-resolution mass spectrometry detected several polyamide-associated chemicals including starting material, plasticizer, thermal stabilizer/antioxidant, and migrating slip additive. Even if polyamide particles and chemicals did not induce an acute inflammatory response, repeated and prolonged exposure of human primary macrophages disclosed a steady increase in the levels of proinflammatory chemokine Interleukin-8 (IL-8/CXCL-8). Moreover, targeted metabolomics disclosed that polyamide particles modulated the kynurenine pathway and some of its key metabolites. The p53-responsive luciferase reporter gene assay showed that particles per se were able to activate p53, being indicative of a genotoxic stress. Polyamide-associated chemicals triggered moderate activation of AhR and elicited anti-androgenic activity. Finally, a high-throughput and non-targeted morphological profiling by Cell Painting assay outlined major sites of bioactivity of polyamide-associated chemicals and indicated putative mechanisms of toxicity in the cells. These findings reveal that the increasing use of polyamide microplastics may pose a potential health risk for the exposed individuals, and it merits more attention.
Topics: Humans; Nylons; Microplastics; Plastics; Tumor Suppressor Protein p53; Plasticizers; Water Pollutants, Chemical
PubMed: 38183898
DOI: 10.1016/j.envint.2023.108412 -
The Science of the Total Environment Mar 2024Microplastics (MPs) pollution has emerged as a critical environmental issue with far-reaching consequences for ecosystems and human health. These are plastic particles... (Review)
Review
Microplastics (MPs) pollution has emerged as a critical environmental issue with far-reaching consequences for ecosystems and human health. These are plastic particles measuring <5 mm and are categorized as primary and secondary based on their origin. Primary MPs are used in various products like cosmetics, scrubs, body wash, and toothpaste, while secondary MPs are generated through the degradation of plastic products. These have been detected in seas, rivers, snow, indoor air, and seafood, posing potential risks to human health through the food chain. Detecting and quantifying MPs are essential to understand their distribution and abundance in the environment. Various microscopic (fluorescence microscopy, scanning electron microscopy) and spectroscopy techniques (FTIR, Raman spectroscopy, X-ray photoelectron spectroscopy) have been reported to analyse MPs. Despite the challenges in scalable removal methods, biological systems have emerged as promising options for eco-friendly MPs remediation. Algae, bacteria, and fungi have shown the potential to adsorb and degrade MPs in wastewater treatment plants (WWTPs) offering hope for mitigating this global crisis. This review examines the sources, impacts, detection, and biological removal of MPs, highlighting future directions in this crucial field of environmental conservation. By fostering global collaboration and innovative research a path towards a cleaner and healthier planet for future generations can be promised.
Topics: Humans; Microplastics; Plastics; Wastewater; Ecosystem; Water Pollutants, Chemical; Environmental Monitoring
PubMed: 38199349
DOI: 10.1016/j.scitotenv.2024.169926 -
World Journal of Microbiology &... Jun 2024Phthalate isomers are key intermediates in the biodegradation of pollutants including waste polyethylene terephthalate (PET) plastics and plasticizers. So far, an... (Review)
Review
Phthalate isomers are key intermediates in the biodegradation of pollutants including waste polyethylene terephthalate (PET) plastics and plasticizers. So far, an increasing number of phthalate isomer-degrading strains have been isolated, and their degradation pathways show significant diversity. In this paper, we comprehensively review the current status of research on the degrading bacteria, degradation characteristics, aerobic and anaerobic degradation pathways, and degradation genes (clusters) of phthalate isomers, and discuss the current shortcomings and challenges. Moreover, the degradation process of phthalate isomers produces many important aromatic precursor molecules, which can be used to produce higher-value derivative chemicals, and the modification of their degradation pathways holds good prospects. Therefore, this review also highlights the current progress made in modifying the phthalate isomer degradation pathway and explores its potential for high-value applications.
Topics: Phthalic Acids; Biodegradation, Environmental; Bacteria; Isomerism; Plasticizers; Environmental Pollutants; Metabolic Networks and Pathways; Polyethylene Terephthalates
PubMed: 38904858
DOI: 10.1007/s11274-024-04060-5 -
Endocrinology Aug 2023Adverse effects associated with exposure to brominated flame retardants have led to regulations for their use and their replacement with organophosphate esters (OPEs)....
Adverse effects associated with exposure to brominated flame retardants have led to regulations for their use and their replacement with organophosphate esters (OPEs). However, little is known about the impact of OPEs on the adrenal, a vital endocrine gland. Here, we used a high-content screening approach to elucidate the effects of OPEs on H295R human adrenal cell phenotypic endpoints and function. The effects of 2,2',4,4'-tetrabromodiphenyl ether (BDE-47), a legacy brominated flame retardant, on H295R cell cytotoxicity, oxidative stress, mitochondria, lysosomes, and lipid droplets were compared with those of 6 OPEs. Most OPEs reduced oxidative stress, increased the numbers of mitochondria, decreased lysosomes, and increased lipid droplets. Two potency ranking approaches, the lowest benchmark concentration/administered equivalent dose methods and Toxicological Prioritization Index analyses, revealed that the triaryl-OPEs (isopropylated triphenyl phosphate [IPPP], tris(methylphenyl) phosphate [TMPP], and triphenyl phosphate [TPHP]) and 1 nontriaryl OPE (tris(1,3-dichloro-2-propyl) phosphate [TDCIPP]) were more potent than BDE-47. The steroidogenic activity of adrenal cells in the presence or absence of forskolin, a steroidogenic stimulus, was determined after exposure to triaryl-OPEs. The basal production of cortisol and aldosterone was increased by IPPP but decreased by TPHP or TMPP exposure; the response to forskolin was not affected by these OPEs. All 3 triaryl OPEs altered the expression of rate-limiting enzymes involved in cholesterol and steroid biosynthesis; CYP11B1 and CYP11B2 were the most prominently affected targets. The OPE chemical-specific effects on cortisol and aldosterone production were best explained by alterations in STAR expression. Thus, the adrenal may be an important target for these endocrine-disrupting chemicals.
Topics: Humans; Flame Retardants; Plasticizers; Aldosterone; Hydrocortisone; Organophosphates; Phosphates; Esters; Phenotype; Environmental Monitoring
PubMed: 37522340
DOI: 10.1210/endocr/bqad119