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1.
J Hazard Mater ; 465: 133459, 2024 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-38219581

RESUMO

Non-antibiotic chemicals in farmlands, including microplastics (MPs) and pesticides, have the potential to influence the soil microbiome and the dissemination of antibiotic resistance genes (ARGs). Despite this, there is limited understanding of the combined effects of MPs and pesticides on microbial communities and ARGs transmission in soil ecosystems. In this study, we observed that low-density polyethylene (LDPE) microplastic enhance the accumulation of pyraclostrobin in earthworms, resulting in reduced weight and causing severe oxidative damage. Analysis of 16 S rRNA amplification revealed that exposure to pyraclostrobin and/or LDPE disrupts the microbial community structure at the phylum and genus levels, leading to reduced alpha diversity in both the soil and earthworm gut. Furthermore, co-exposure to LDPE and pyraclostrobin increased the relative abundance of ARGs in the soil and earthworm gut by 2.15 and 1.34 times, respectively, compared to exposure to pyraclostrobin alone. It correlated well with the increasing relative abundance of genera carrying ARGs. Our findings contribute novel insights into the impact of co-exposure to MPs and pesticides on soil and earthworm microbiomes, highlighting their role in promoting the transfer of ARGs. This knowledge is crucial for managing the risk associated with the dissemination of ARGs in soil ecosystems.


Assuntos
Microbiota , Oligoquetos , Praguicidas , Estrobilurinas , Animais , Antibacterianos/farmacologia , Polietileno/farmacologia , Genes Bacterianos , Plásticos , Solo , Resistência Microbiana a Medicamentos , Microplásticos/farmacologia , Praguicidas/análise , Microbiologia do Solo
2.
Drug Deliv ; 28(1): 873-883, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33960250

RESUMO

The aim of this investigation was to develop an etomidate intravenous lipid emulsion (ETM-ILE) and evaluate its properties in vitro and in vivo. Etomidate (ETM) is a hydrophobic drug, and organic solvents must be added to an etomidate injectable solution (ETM-SOL) to aid dissolution, that causes various adverse reactions on injection. Lipid emulsions are a novel drug formulation that can improve drug loading and reduce adverse reactions. ETM-ILE was prepared using high-pressure homogenization. Univariate experiments were performed to select key conditions and variables. The proportion of oil, egg lecithin, and poloxamer 188 (F68) served as variables for the optimization of the ETM-ILE formulation by central composite design response surface methodology. The optimized formulation had the following characteristics: particle size, 168.0 ± 0.3 nm; polydispersity index, 0.108 ± 0.028; zeta potential, -36.4 ± 0.2 mV; drug loading, 2.00 ± 0.01 mg/mL; encapsulation efficiency, 97.65% ± 0.16%; osmotic pressure, 292 ± 2 mOsmol/kg and pH value, 7.63 ± 0.07. Transmission electron microscopy images showed that the particles were spherical or spheroidal, with a diameter of approximately 200 nm. The stability study suggested that ETM-ILE could store at 4 ± 2 °C or 25 ± 2 °C for 12 months. Safety tests showed that ETM-ILE did not cause hemolysis or serious vascular irritation. The results of the pharmacokinetic study found that ETM-ILE was bioequivalent to ETM-SOL. However, a higher concentration of ETM was attained in the liver, spleen, and lungs after administration of ETM-ILE than after administration of ETM-SOL. This study found that ETM-ILE had great potential for clinical applications.


Assuntos
Anestésicos Intravenosos/administração & dosagem , Anestésicos Intravenosos/farmacocinética , Etomidato/administração & dosagem , Etomidato/farmacocinética , Emulsões Gordurosas Intravenosas/química , Anestésicos Intravenosos/farmacologia , Animais , Química Farmacêutica , Estabilidade de Medicamentos , Etomidato/farmacologia , Concentração de Íons de Hidrogênio , Lecitinas/química , Masculino , Tamanho da Partícula , Poloxâmero/química , Coelhos , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Óleo de Soja/química , Propriedades de Superfície
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